Substitute diphenylamine compounds use thereof as antitumor agents

FIELD OF THE INVENTION

The present invention relates to the field of medicine. Specifically to a substituted diphenylamine compounds and uses thereof as antitumor agents.

BACKGROUND OF THE INVENTION

The following compounds, which can be used as intermediates to synthetise a kind of multi-halogenated acridone compounds having fluorescence and pharmaceutical activity, were reported in patent CN101391981A. The invention discloses compounds KC1(IV-A), KC2(IV-B), KC3(IV-D), KC4(IV-E), KC5(IV-H) and KC6(IV-C), but there are no bioactivity reported. The compound KC1(XXIX) was also reported in Pesticide Science (1988), 24(2), 111-21, showing fungicidal activity against grape downy mildew (Plasmopora viticola).

##STR00002##

The compounds having the following general formulas were reported as insecticides, acaricides, fungicides, herbicides, rodenticide or others in the prior art:

##STR00003##

Such as patents BR7900462, CH626323, CN1188757, DE2509416, DE2642147, DE2642148, EP26743, EP60951, GB1544078, GB1525884, JP58113151, JP64001774, JP01186849, WO2002060878, WO2005035498, WO2009037707, U.S. Pat. No. 3,948,957, U.S. Pat. No. 3,948,990, U.S. Pat. No. 4,041,172, U.S. Pat. No. 4,152,460, U.S. Pat. No. 4,187,318, U.S. Pat. No. 4,215,145, U.S. Pat. No. 4,304,791, U.S. Pat. No. 4,316,988, U.S. Pat. No. 4,407,820, U.S. Pat. No. 4,459,304, U.S. Pat. No. 4,670,596 and so on, and ACS Symposium Series (1992), 504 (Synth. Chem. Agrochem. III), 336-48; Journal of the Chemical Society (1951), 110-15, etc. all reported the compounds having above general formulas.

In addition, the compounds of the following general formulas were mentioned in Chemische Berichte (1962), 95 1711-21; Chemische Berichte (1963), 96(7), 1936-44; Journal of Organic Chemistry (1954), 19, 1641-5; Journal of the Chemical Society; Transactions (1913), 103 982-8 and Journal of the Chemical Society, Transactions (1921), 119, 187-92 and so on, but without any bioactivity reported:

##STR00004##

The compounds having the following general formulas as fungicide were reported in patent WO2012171484:

##STR00005##

The compounds having the following general formulas as fungicide were reported in patent WO2011116671:

##STR00006##

The compounds having the structure of general formula I were not reported in the prior art as antitumor agents.

SUMMARY OF THE INVENTION

The object of the present invention is to provide substituted diphenylamine compounds having general formula I, which can be applied to antitumor agents.

Detailed description of the invention is as follows:

Substituted diphenylamine compounds use thereof as antitumor agents, the compounds having the structure of general formula I:

##STR00007##

Wherein:

R.sub.1 is selected from H, C.sub.1-C.sub.8alkyl, C.sub.3-C.sub.8cycloalkyl, C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8halo alkylcarbonyl, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8alkylamino carbonyl, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkylaminothio, C.sub.2-C.sub.8dialkylaminothio, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8alkynyl, C.sub.2-C.sub.8haloalkenyl, C.sub.2-C.sub.8haloalkynyl, aryl C.sub.1-C.sub.8alkyl or CO--X--CO.sub.2R.sub.12, in which X is selected from (CHR.sub.12)n, CR.sub.12.dbd.CR.sub.13 or C.sub.6H.sub.4, n=1-6;

R.sub.2 and R.sub.6 may be the same or different, respectively selected from H, halogen, CN, NO.sub.2, COOH, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8halo alkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8alkyl, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.3 and R.sub.5 may be the same or different, respectively selected from H, halogen, CN, NO.sub.2, COOH, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8halo alkyl, C.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8alkylamino, C.sub.1-C.sub.8halo alkylamino, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkylcarbonyloxy, C.sub.1-C.sub.8 alkoxycarbonyloxy, C.sub.1-C.sub.8alkylaminocarbonyloxy, C.sub.1-C.sub.8alkylsulfonyloxy, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8halo alkoxyC.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8 alkoxy, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.4 is selected from H, halogen, CN, NO.sub.2, COOH, CO.sub.2Na, CO.sub.2NH.sub.4, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8halo alkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8haloalkoxyC.sub.1-C.sub.8haloalkoxy, SO.sub.2NR.sub.12R.sub.13, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.7 is selected from Cl or CH.sub.3;

R.sub.8 is selected from H, halogen, OH, CN, NO.sub.2, COOH, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8alkylamino, C.sub.1-C.sub.8halo alkylamino, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.1-C.sub.8alkylsulfonyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.2-C.sub.8dialkylamino, C.sub.3-C.sub.8 alkenyloxy, C.sub.3-C.sub.8haloalkenyloxy, C.sub.3-C.sub.8alkynyloxy, C.sub.3-C.sub.8halo alkynyloxy, C.sub.1-C.sub.8alkylcarbonyloxy, C.sub.1-C.sub.8alkylcarbonylamino, C.sub.1-C.sub.8alkylsulfonyloxy, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8 alkoxy, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryloxy, arylamino, arylmethoxy, arylmethylamino, heteroaryloxy or heteroarylamino, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.9 is selected from H, halogen, NO.sub.2, CN, C(.dbd.O)NR.sub.12R.sub.13, C(.dbd.S)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkylaminocarbonyl, C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8haloalkyl or C.sub.1-C.sub.8alkylsulfonyl;

R.sub.10 is selected from H, halogen, OH, CN, NO.sub.2, COOH, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8alkylamino, C.sub.1-C.sub.8halo alkylamino, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.1-C.sub.8alkylsulfonyl, C.sub.2-C.sub.8dialkylamino, C.sub.3-C.sub.8alkenyloxy, C.sub.3-C.sub.8haloalkenyloxy, C.sub.3-C.sub.8 alkynyloxy, C.sub.3-C.sub.8halo alkynyloxy, C.sub.1-C.sub.8alkylcarbonyloxy, C.sub.1-C.sub.8alkylcarbonylamino, C.sub.1-C.sub.8alkylsulfonyloxy, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8 alkoxy or C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8alkoxy;

R.sub.11 is selected from CN or NO.sub.2,

R.sub.12 and R.sub.13 may be the same or different, respectively selected from H, C.sub.1-C.sub.6alkyl or C.sub.3-C.sub.6cycloalkyl;

R.sub.14 is selected from halogen, NO.sub.2, CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkoxycarbonyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6haloalkenyloxy, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6alkynyloxy, C.sub.3-C.sub.6haloalkynyloxy, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylcarbonyl, C.sub.1-C.sub.6alkylamino, C.sub.1-C.sub.6haloalkylamino, C.sub.2-C.sub.8dialkylamino, C.sub.1-C.sub.6alkylcarbonylamino, C.sub.1-C.sub.6haloalkylcarbonylamino, C.sub.1-C.sub.6alkylaminocarbonyl or C.sub.1-C.sub.6haloalkylaminocarbonyl;

Or the salts of the compounds having general formula I.

Furthermore, the preferred uses as antitumor compounds of general formula I of this invention include two kinds of compounds:

The first kind of compound is: R.sub.7 is Cl, R.sub.9 and R.sub.11 are CN in compounds of general formula I, the structures are as general formula II:

##STR00008##

Wherein:

R.sub.1 is selected from H, C.sub.1-C.sub.8alkyl, C.sub.3-C.sub.8cycloalkyl, C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8halo alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8alkylamino carbonyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8alkynyl, C.sub.2-C.sub.8haloalkenyl, C.sub.2-C.sub.8haloalkynyl, aryl C.sub.1-C.sub.8alkyl or CO--X--CO.sub.2R.sub.12, in which X is selected from (CHR.sub.12)n, CR.sub.12.dbd.CR.sub.13 or C.sub.6H.sub.4, n=1-6;

R.sub.2 and R.sub.6 may be the same or different, respectively selected from H, halogen, CN, NO.sub.2, COOH, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8halo alkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8alkyl, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.3 and R.sub.5 may be the same or different, respectively selected from H, halogen, CN, NO.sub.2, COOH, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8halo alkyl, C.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8alkylamino, C.sub.1-C.sub.8halo alkylamino, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkylcarbonyloxy, C.sub.1-C.sub.8 alkoxycarbonyloxy, C.sub.1-C.sub.8alkylaminocarbonyloxy, C.sub.1-C.sub.8alkylsulfonyloxy, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8haloalkoxyC.sub.1-C.sub.8haloalkoxy, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8 alkoxy, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.4 is selected from H, halogen, CN, NO.sub.2, COOH, CO.sub.2Na, CO.sub.2NH.sub.4, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8halo alkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8haloalkoxyC.sub.1-C.sub.8haloalkoxy, SO.sub.2NR.sub.12R.sub.13, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl or arylaminocarbonyl, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.8 and R.sub.10 may be the same or different, respectively selected from H, halogen, OH, CN, NO.sub.2, COOH, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, C.sub.1-C.sub.8alkylamino, C.sub.1-C.sub.8haloalkylamino, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio, C.sub.1-C.sub.8alkylsulfonyl, C.sub.2-C.sub.8dialkylamino, C.sub.3-C.sub.8alkenyloxy, C.sub.3-C.sub.8haloalkenyloxy, C.sub.3-C.sub.8 alkynyloxy, C.sub.3-C.sub.8haloalkynyloxy, C.sub.1-C.sub.8alkylcarbonyloxy, C.sub.1-C.sub.8alkylcarbonylamino, C.sub.1-C.sub.8alkylsulfonyloxy, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8 alkoxy or C.sub.1-C.sub.8alkoxycarbonylC.sub.1-C.sub.8 alkoxy;

R.sub.12 and R.sub.13 may be the same or different, respectively selected from H, C.sub.1-C.sub.6alkyl or C.sub.3-C.sub.6cycloalkyl;

R.sub.14 is selected from halogen, NO.sub.2, CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6halo alkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6 alkoxycarbonyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6haloalkenyloxy, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6alkynyloxy, C.sub.3-C.sub.6haloalkynyloxy, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylcarbonyl, C.sub.1-C.sub.6alkylamino, C.sub.1-C.sub.6halo alkylamino, C.sub.2-C.sub.8dialkylamino, C.sub.1-C.sub.6alkylcarbonylamino, C.sub.1-C.sub.6halo alkylcarbonylamino, C.sub.1-C.sub.6alkylamino carbonyl or C.sub.1-C.sub.6halo alkylamino carbonyl;

Or the salts of the compounds having general formula II.

The preferred uses as antitumor compounds of general formula II of this invention are:

R.sub.1 is selected from H, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4halo alkylcarbonyl, C.sub.1-C.sub.4 alkoxycarbonyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4 alkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonylC.sub.1-C.sub.4alkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4haloalkynyl, benzyl, phenethyl or CO--X--CO.sub.2R.sub.12, in which X is selected from (CHR.sub.12)n, CR.sub.12.dbd.CR.sub.13 or C.sub.6H.sub.4, n=1-3;

R.sub.2 and R.sub.6 may be the same or different, respectively selected from H, Cl, Br, F, CN, NO.sub.2, COOH, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4halo alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4halo alkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4halo alkylthio, C.sub.2-C.sub.4 alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxycarbonylC.sub.1-C.sub.4alkyl, or the following groups unsubstituted or substituted with 1-3 R.sub.14: phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.3 and R.sub.5 may be the same or different, respectively selected from H, Cl, Br, F, CN, NO.sub.2, COOH, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylamino, C.sub.1-C.sub.4halo alkylamino, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4haloalkylthio, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4 alkoxycarbonyl, C.sub.1-C.sub.4 alkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxycarbonylC.sub.1-C.sub.4alkyl, or the following groups unsubstituted or substituted with 1-3 R.sub.14: phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.4 is selected from H, Cl, Br, F, CN, NO.sub.2, COOH, CO.sub.2Na, CO.sub.2NH.sub.4, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4 alkoxycarbonyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4 alkoxycarbonylC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkoxy, SO.sub.2NHCH.sub.3, SO.sub.2N(CH.sub.3).sub.2, or the following groups unsubstituted or substituted with 1-3 R.sub.14: phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl or phenylaminocarbonyl, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.8 and R.sub.10 may be the same or different, respectively selected from Cl, Br, F, OH, CN, NO.sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4halo alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4halo alkoxy, C.sub.1-C.sub.4alkylamino, C.sub.1-C.sub.4halo alkylamino, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4halo alkylthio, C.sub.1-C.sub.4alkylsulfonyl, C.sub.2-C.sub.6dialkylamino, C.sub.3-C.sub.4 alkenyloxy, C.sub.3-C.sub.4haloalkenyloxy, C.sub.3-C.sub.4alkynyloxy, C.sub.3-C.sub.4haloalkynyloxy, C.sub.1-C.sub.4alkylcarbonyloxy, C.sub.1-C.sub.4alkylcarbonylamino, C.sub.1-C.sub.4alkylsulfonyloxy, C.sub.1-C.sub.4 alkoxyC.sub.1-C.sub.4alkoxy or C.sub.1-C.sub.4alkoxycarbonylC.sub.1-C.sub.4 alkoxy;

R.sub.12 and R.sub.13 may be the same or different, respectively selected from H or C.sub.1-C.sub.4alkyl; R.sub.14 is selected from F, Cl, Br, NO.sub.2, CN, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4halo alkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4 alkoxycarbonyl or C.sub.1-C.sub.4alkylaminocarbonyl;

Or the salts of the compounds having general formula II.

Furthermore, the preferred uses as antitumor compounds of general formula II of this invention are:

R.sub.1 is selected from H, CH.sub.3, acetyl, methylsulfonyl, benzyl or phenethyl;

R.sub.2 and R.sub.6 may be the same or different, respectively selected from H, F, Cl, Br, CN, NO.sub.2, COOH, CONH.sub.2, CONHCH.sub.3, CON(CH.sub.3).sub.2, CONHCH(CH.sub.3).sub.2, CONHC(CH.sub.3).sub.3, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, C(CH.sub.3).sub.3, ClCH.sub.2, CF.sub.3, CH.sub.3O, C.sub.2H.sub.5O, CF.sub.3O, CF.sub.3CH.sub.2O, CH.sub.3S, CH.sub.3OCO or CH.sub.3OCH.sub.2;

R.sub.3 and R.sub.5 may be the same or different, respectively selected from H, F, Cl, Br, CN, NO.sub.2, COOH, CONH.sub.2, CONHCH.sub.3, CON(CH.sub.3).sub.2, CONHCH(CH.sub.3).sub.2, CONHC(CH.sub.3).sub.3, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, C(CH.sub.3).sub.3, ClCH.sub.2, CF.sub.3, CH.sub.3O, C.sub.2H.sub.5O, CF.sub.3O, CF.sub.3CH.sub.2O, CH.sub.3S, CH.sub.3OCO or CH.sub.3OCH.sub.2;

R.sub.4 is selected from H, F, Cl, Br, CN, NO.sub.2, COOH, CO.sub.2Na, CO.sub.2NH.sub.4, CONH.sub.2, CONHCH.sub.3, CON(CH.sub.3).sub.2, CONHCH(CH.sub.3).sub.2, CONHC(CH.sub.3).sub.3, CF.sub.3, CF.sub.3O, CH.sub.3OCO, C.sub.2H.sub.5OCO, CH.sub.3SO.sub.2, SO.sub.2NHCH.sub.3, SO.sub.2N(CH.sub.3).sub.2, phenoxycarbonyl, phenylaminocarbonyl, 4-CH.sub.3-phenylaminocarbonyl or 4-Cl-phenylaminocarbonyl;

R.sub.8 and R.sub.10 may be the same or different, respectively selected from Cl, F, CH.sub.3O, CF.sub.3O, CF.sub.3CH.sub.2O, CH.sub.3NH, (CH.sub.3).sub.2N, (C.sub.2H.sub.5).sub.2N, CF.sub.3CH.sub.2NH, ClCH.sub.2CH.sub.2NH, CH.sub.3S, C.sub.2H.sub.5S, CH.sub.3SO.sub.2, C.sub.2H.sub.5SO.sub.2, (CH.sub.3).sub.2N, CH.sub.2.dbd.CHCH.sub.2O, C.ident.CCH.sub.2O, ClC.ident.CCH.sub.2O, IC.ident.CCH.sub.2O, CH.sub.3CO.sub.2, CH.sub.3CONH, CH.sub.3OCH.sub.2CH.sub.2O, C.sub.2H.sub.5OCH.sub.2CH.sub.2O, CH.sub.3OC(.dbd.O)CH.sub.2O or CH.sub.3OC(.dbd.O)CH.sub.2CH.sub.2O;

Or the salts formed from the compounds of general formula II with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

Even more preferred uses as antitumor compounds of general formula II of this invention are:

R.sub.1 is selected from H;

R.sub.2 is selected from H, F, Cl, Br, CH.sub.3, C.sub.2H.sub.5, NO.sub.2 or CN;

R.sub.3 is selected from H, F, Cl, Br, CH.sub.3 or CF.sub.3;

R.sub.4 is selected from H, F, Cl, Br, CF.sub.3, CF.sub.3O, CH.sub.3OCO, CN, NO.sub.2, COOH, CO.sub.2Na, phenylaminocarbonyl or 4-Cl-phenylaminocarbonyl;

R.sub.5 is selected from H, Cl, Br, CH.sub.3 or CF.sub.3;

R.sub.6 is selected from H, F, Cl, Br, CH.sub.3, C.sub.2H.sub.5, NO.sub.2 or CN;

R.sub.8 is selected from Cl, CH.sub.3O, CH.sub.3NH, (CH.sub.3).sub.2N or (C.sub.2H.sub.5).sub.2N;

R.sub.10 is selected from Cl, CH.sub.3O or CH.sub.3NH;

Or the salts formed from the compounds of general formula II with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

The more preferred uses as antitumor compounds of general formula II of this invention are:

R.sub.1, R.sub.3 and R.sub.5 are selected from H;

R.sub.2 and R.sub.6 are selected from H, Cl or Br;

R.sub.4 is selected from H, Cl, Br, NO.sub.2, CF.sub.3, CF.sub.3O or CH.sub.3OCO;

R.sub.8 and R.sub.10 are selected from Cl;

Or the salts formed from the compounds of general formula II with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

The most preferred uses as antitumor compounds of general formula II of this invention are:

##STR00009## ##STR00010##

The following structure in the most preferred uses as antitumor compounds of general formula II of this invention has never been reported before (refer to compound Table 6-112):

##STR00011##

The second kind of compound of the preferred uses as antitumor compounds of general formula I of this invention is: R.sub.7 is CH.sub.3, R.sub.10 is H, R.sub.11 is NO.sub.2, the structures are as general formula III:

##STR00012##

Wherein:

R.sub.1 is selected from H, C.sub.1-C.sub.8alkyl, C.sub.3-C.sub.8cycloalkyl, C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8halo alkylcarbonyl, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8alkylamino carbonyl, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkylaminothio, C.sub.2-C.sub.8dialkylaminothio or CO--X--CO.sub.2R.sub.12, in which X is selected from (CHR.sub.12)n, CR.sub.12.dbd.CR.sub.13 or C.sub.6H.sub.4, n=1-6;

R.sub.2 and R.sub.6 may be the same or different, respectively selected from H, halogen, CN, NO.sub.2, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxycarbonylC.sub.1-C.sub.8alkyl, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.3 and R.sub.5 may be the same or different, respectively selected from H, halogen, CN, NO.sub.2, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8halo alkyl, C.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8alkylamino, C.sub.1-C.sub.8halo alkylamino, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkylcarbonyloxy, C.sub.1-C.sub.8alkoxycarbonyloxy, C.sub.1-C.sub.8alkylaminocarbonyloxy, C.sub.1-C.sub.8alkylsulfonyloxy, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8halo alkoxyC.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8 alkoxy, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.4 is selected from H, halogen, CN, NO.sub.2, COOH, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8 alkoxycarbonylC.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxyC.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8haloalkoxyC.sub.1-C.sub.8haloalkoxy, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl, arylaminocarbonyl or heteroaryloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.8 is selected from H, halogen, C.sub.1-C.sub.8halo alkyl, C.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8halo alkoxy, C.sub.1-C.sub.8alkylamino, C.sub.1-C.sub.8halo alkylamino, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8halo alkylthio, C.sub.1-C.sub.8alkylsulfonyl, C.sub.3-C.sub.8 cyclo alkyl, C.sub.2-C.sub.8dialkylamino, C.sub.3-C.sub.8 alkenyloxy, C.sub.3-C.sub.8haloalkenyloxy, C.sub.3-C.sub.8alkynyloxy, C.sub.3-C.sub.8haloalkynyloxy, C.sub.1-C.sub.8alkylcarbonyloxy, C.sub.1-C.sub.8alkylcarbonylamino, C.sub.1-C.sub.8alkylsulfonyloxy, C.sub.1-C.sub.8 alkoxyC.sub.1-C.sub.8 alkoxy, C.sub.1-C.sub.8alkoxycarbonylC.sub.1-C.sub.8alkoxy, or the following groups unsubstituted or substituted with 1-5 R.sub.14: aryloxy, arylamino, arylmethoxy, arylmethylamino, heteroaryloxy or heteroarylamino, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.9 is selected from H, halogen, NO.sub.2, CN, C(.dbd.O)NR.sub.12R.sub.13, C(.dbd.S)NR.sub.12R.sub.13, C.sub.1-C.sub.8alkylamino carbonyl, C.sub.1-C.sub.8 alkoxycarbonyl, C.sub.1-C.sub.8halo alkyl or C.sub.1-C.sub.8alkylsulfonyl;

R.sub.12 and R.sub.13 may be the same or different, respectively selected from H or C.sub.1-C.sub.6alkyl;

R.sub.14 is selected from halogen, NO.sub.2, CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkoxycarbonyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6haloalkenyloxy, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6alkynyloxy, C.sub.3-C.sub.6haloalkynyloxy, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylcarbonyl, C.sub.1-C.sub.6alkylamino, C.sub.1-C.sub.6halo alkylamino, C.sub.2-C.sub.8dialkylamino, C.sub.1-C.sub.6alkylcarbonylamino, C.sub.1-C.sub.6halo alkylcarbonylamino, C.sub.1-C.sub.6alkylaminocarbonyl or C.sub.1-C.sub.6haloalkylaminocarbonyl;

Or the salts of the compounds having general formula III.

The preferred uses as antitumor compounds of general formula III of this invention are:

R.sub.1 is selected from H, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4haloalkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonyl, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4halo alkylthio, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4 alkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4 alkoxycarbonylC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylaminothio, C.sub.2-C.sub.4dialkylaminothio or CO--X--CO.sub.2R.sub.12, in which X is selected from (CHR.sub.12)n, CR.sub.12.dbd.CR.sub.13 or C.sub.6H.sub.4, n=1-3;

R.sub.2 and R.sub.6 may be the same or different, respectively selected from H, halogen, CN, NO.sub.2, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxycarbonylC.sub.1-C.sub.4alkyl, or the following groups unsubstituted or substituted with 1-4 R.sub.14: phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.3 and R.sub.5 may be the same or different, respectively selected from H, halogen, CN, NO.sub.2, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4halo alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylamino, C.sub.1-C.sub.4haloalkylamino, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4halo alkylthio, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonyl or C.sub.1-C.sub.4 alkoxyC.sub.1-C.sub.4alkyl;

R.sub.4 is selected from H, halogen, CN, NO.sub.2, COOH, C(.dbd.O)NR.sub.12R.sub.13, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4halo alkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonyl, C.sub.1-C.sub.4 alkoxyC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4 alkoxycarbonylC.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkoxy, or the following groups unsubstituted or substituted with 1-4 R.sub.14: phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl or pyridyloxy, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.8 is selected from H, halogen, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylamino, C.sub.1-C.sub.4haloalkylamino, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4alkylsulfonyl, C.sub.2-C.sub.4dialkylamino, C.sub.3-C.sub.4alkenyloxy, C.sub.3-C.sub.4haloalkenyloxy, C.sub.3-C.sub.6alkynyloxy, C.sub.1-C.sub.4alkylcarbonyloxy, C.sub.1-C.sub.4alkylcarbonylamino, C.sub.1-C.sub.4alkylsulfonyloxy, C.sub.1-C.sub.4 alkoxyC.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxycarbonylC.sub.1-C.sub.4alkoxy, or the following groups unsubstituted or substituted with 1-3 R.sub.14: phenoxy, phenylamino, benzyloxy, benzylamino, pyridyloxy or pyridylamino, and when the number of the substitutes is more than 1, R.sub.14 may be the same or different;

R.sub.9 is selected from Cl, Br, F, NO.sub.2, CN, C(.dbd.O)NR.sub.12R.sub.13, C(.dbd.S)NR.sub.12R.sub.13, CO.sub.2CH.sub.3, CF.sub.3 or CH.sub.3SO.sub.2;

R.sub.12 and R.sub.13 may be the same or different, respectively selected from H or C.sub.1-C.sub.3alkyl;

R.sub.14 is selected from halogen, NO.sub.2, CN, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylcarbonyl, C.sub.1-C.sub.3 alkoxycarbonyl, C.sub.1-C.sub.3alkylamino, C.sub.2-C.sub.4dialkylamino, C.sub.1-C.sub.3alkylcarbonylamino or C.sub.1-C.sub.3alkylaminocarbonyl;

Or the salts of the compounds having general formula III.

Furthermore, the preferred uses as antitumor compounds of general formula III of this invention are:

R.sub.1 is selected from H, CH.sub.3, C.sub.2H.sub.5, cyclopropyl, formyl, acetyl, COCF.sub.3, CO.sub.2CH.sub.3, CO.sub.2C.sub.2H.sub.5, SCCl.sub.3, SO.sub.2CH.sub.3, SO.sub.2C.sub.2H.sub.5, CH.sub.2OCH.sub.3, CH.sub.2OC.sub.2H.sub.5, CH.sub.2CH.sub.2OCH.sub.3, COCH.sub.2OCH.sub.3, CH.sub.2COOCH.sub.3, SNHCH.sub.3, SN(CH.sub.3).sub.2, COCH.sub.2CO.sub.2H, COCH.sub.2CO.sub.2CH.sub.3, COCH.sub.2CH.sub.2CO.sub.2H, COCH.sub.2CH.sub.2CO.sub.2CH.sub.3, COCHCH.sub.3CO.sub.2H, COCHCH.sub.3CO.sub.2CH.sub.3, COC.sub.6H.sub.4CO.sub.2H, COC.sub.6H.sub.4CO.sub.2CH.sub.3, COCH.dbd.CHCO.sub.2H or COCH.dbd.CHCO.sub.2CH.sub.3;

R.sub.2 and R.sub.6 may be the same or different, respectively selected from H, Cl, Br, F, CN, NO.sub.2, C(.dbd.O)NH.sub.2, C(.dbd.O)NHCH.sub.3, C(.dbd.O)N(CH.sub.3).sub.2, CH.sub.3, C.sub.2H.sub.5, CF.sub.3, OCH.sub.3, OC.sub.2H.sub.5, OCF.sub.3, SO.sub.2CH.sub.3, SO.sub.2C.sub.2H.sub.5, COCH.sub.3, CO.sub.2CH.sub.3, CO.sub.2C.sub.2H.sub.5, phenoxy, phenylamino, phenoxycarbonyl or phenylaminocarbonyl;

R.sub.3 and R.sub.5 may be the same or different, respectively selected from H, Cl, Br, F, CN, NO.sub.2, C(.dbd.O)NH.sub.2, CH.sub.3, CF.sub.3, OCH.sub.3, OCF.sub.3, NHCH.sub.3, SCH.sub.3, SO.sub.2CH.sub.3, SO.sub.2C.sub.2H.sub.5, COCH.sub.3, CO.sub.2CH.sub.3, CO.sub.2C.sub.2H.sub.5 or CH.sub.2OCH.sub.3;

R.sub.4 is selected from H, Cl, Br, F, CN, NO.sub.2, CO.sub.2H, C(.dbd.O)NH.sub.2, C(.dbd.O)NHCH.sub.3, C(.dbd.O)N(CH.sub.3).sub.2, CH.sub.3, CF.sub.3, CF(CF.sub.3).sub.2, OCF.sub.3, OCH.sub.2CF.sub.3, OCF.sub.2CHFCF.sub.3, SO.sub.2CH.sub.3, SO.sub.2C.sub.2H.sub.5, COCH.sub.3, CO.sub.2CH.sub.3, CO.sub.2C.sub.2H.sub.5, phenoxy, phenylamino, phenylcarbonyl, benzylcarbonyl, phenoxycarbonyl, phenylaminocarbonyl, pyridyloxy or 3-chloro-5-(trifluoromethyl)pyridin-2-yloxy;

R.sub.8 is selected from H, Cl, Br, F, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3alkylamino, C.sub.1-C.sub.3haloalkylamino, SCH.sub.3, SC.sub.2H.sub.5, N(CH.sub.3).sub.2, N(C.sub.2H.sub.5).sub.2, OCH.sub.2OCH.sub.3, phenoxy, phenylamino, benzyloxy, benzylamino, 4-chlorophenoxy, 4-chlorophenylamino, 2-chloro-4-(trifluoromethyl)phenoxy, 2-chloro-4-(trifluoromethyl)phenylamino, 3-chloro-5-(trifluoromethyl)pyridin-2-yloxy or 3-chloro-5-(trifluoromethyl)pyridin-2-ylamino;

R.sub.9 is NO.sub.2;

Or the salts formed from the compounds of general formula III with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

Even more preferred uses as antitumor compounds of general formula III of this invention are:

R.sub.1 is selected from H or CH.sub.3;

R.sub.2 and R.sub.6 may be the same or different, respectively selected from H, Cl, Br, F, CN, NO.sub.2, C(.dbd.O)NH.sub.2, C(.dbd.O)NHCH.sub.3, C(.dbd.O)N(CH.sub.3).sub.2, CH.sub.3, CF.sub.3, CO.sub.2CH.sub.3 or phenoxycarbonyl;

R.sub.3 and R.sub.5 may be the same or different, respectively selected from H, Cl, Br, F, CN, NO.sub.2, CH.sub.3, CF.sub.3 or OCH.sub.3;

R.sub.4 is selected from H, Cl, Br, F, CN, NO.sub.2, CO.sub.2H, C(.dbd.O)NH.sub.2, C(.dbd.O)NHCH.sub.3, CH.sub.3, CF.sub.3, OCF.sub.2CHFCF.sub.3, CO.sub.2CH.sub.3 or 3-chloro-5-(trifluoromethyl)pyridin-2-yloxy;

R.sub.8 is selected from H, Cl, OCH.sub.3, OCH.sub.2CF.sub.3, NHCH.sub.3, SCH.sub.3 or N(CH.sub.3).sub.2;

R.sub.9 is NO.sub.2,

Or the salts formed from the compounds of general formula III with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

The more preferred uses as antitumor compounds of general formula III of this invention are:

R.sub.1, R.sub.3 and R.sub.5 are selected from H;

R.sub.2 is selected from Cl or F;

R.sub.4 is selected from H, Cl, CN, NO.sub.2 or CF.sub.3;

R.sub.6 is selected from F, Cl, CN or NO.sub.2;

R.sub.8 is selected from H, Cl or OCH.sub.2CF.sub.3;

R.sub.9 is NO.sub.2,

Or the salts formed from the compounds of general formula III with hydrochloric acid, sulfuric acid, nitric acid, hydrogen carbonic acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid.

The most preferred uses as antitumor compounds of general formula III of this invention are:

##STR00013## ##STR00014##

The terms used above to definite the compounds of general formula I represent substitutes as follow:

The "halogen" or "halo" is fluorine, chlorine, bromine or iodine.

The "alkyl" stands for straight or branched chain alkyl, such as methyl, ethyl, propyl, isopropyl or tert-butyl.

The "cycloalkyl" is substituted or unsubstituted cyclic alkyl, such as cyclopropyl, cyclopentyl or cyclohexyl. The substitute(s) is(are) methyl, halogen, etc.

The "haloalkyl" stands for straight or branched chain alkyl, in which hydrogen atoms can be all or partly substituted with halogen, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc.

The "alkoxy" refers to straight or branched chain alkyl, which is linked to the structure by oxygen atom.

The "haloalkoxy" refers to straight or branched chain alkoxy, in which hydrogen atoms may be all or partly substituted with halogen, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy, etc.

The "alkylthio" refers to straight or branched chain alkyl, which is linked to the structure by sulfur atom.

The "haloalkylthio" refers to straight or branched chain alkylthio, in which hydrogen atoms may be all or partly substituted with halogen, such as chloromethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, etc.

The "alkylamino" refers to straight or branched chain alkyl, which is linked to the structure by nitrogen atom.

The "haloalkylamino" refers to straight or branched chain alkylamino, in which hydrogen atoms may be all or partly substituted with halogen.

The "alkenyl" refers to straight or branched chain alkenyl, such as ethenyl, 1-propenyl, 2-propenyl and different isomer of butenyl, pentenyl and hexenyl. Alkenyl also includes polyene, such as propa-1,2-dienyl and hexa-2,4-dienyl.

The "haloalkenyl" stands for straight or branched chain alkenyl, in which hydrogen atoms can be all or partly substituted with halogen.

The "alkynyl" refers to straight or branched chain alkynyl, such as ethynyl, 1-propynyl, 2-propynyl and different isomer of butynyl, pentynyl and hexynyl. Alkynyl also includes groups including more than one triple bonds, such as hexa-2,5-diynyl.

The "haloalkynyl" stands for straight or branched chain alkynyl, in which hydrogen atoms can be all or partly substituted with halogen.

The alkenyloxy refers to straight or branched chain alkenyl, which is linked to the structure by oxygen atom.

The alkynyloxy refers to straight or branched chain alkynyl, which is linked to the structure by oxygen atom.

The alkylsulfonyl refers to straight or branched chain alkyl, which is linked to the structure by sulfuryl(--SO.sub.2--), such as SO.sub.2CH.sub.3.

The alkylcarbonyl refers to straight or branched chain alkyl, which is linked to the structure by carbonyl(--CO--), such as CH.sub.3CO--, CH.sub.3CH.sub.2CO--.

The alkylcarbonyloxy: such as CH.sub.3COO--, CH.sub.3CH.sub.2NHCOO--.

The alkylcarbonylamino: such as CH.sub.3CONH--, CH.sub.3CH.sub.2NHCONH--.

The alkylsulfonyloxy: such as alkyl-S(O).sub.2--O--.

The alkoxycarbonyl: alkyl-O--CO--.

The phenylaminocarbonyl: phenyl-NH--CO--.

The aryl in aryl, arylmethyl, aryloxy, arylamino, arylcarbonyl, arylmethylcarbonyl, aryloxycarbonyl and arylaminocarbonyl refers to phenyl or naphthyl, etc.

The "heteroaryl" stands for five member ring or six member ring containing one or more N, O, S hetero atoms. Such as furanyl, pyrazolyl, thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, etc.

Part of the substitutes of R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.8 and R.sub.10 in formula I are separately listed in table 1, table 2, table 3, table 4 and table 5, but without being restricted thereby.

##STR00015##

TABLE-US-00001 TABLE 1 substitute R.sub.1 R.sub.1 R.sub.1 R.sub.1 H CO.sub.2CH.sub.3 CH.sub.2C.ident.C--Cl CH.sub.3 CO.sub.2CH.sub.2CH.sub.3 CH.sub.2C.ident.CCH.sub.3 C.sub.2H.sub.5 SO.sub.2CH.sub.2CH.sub.3 PhCH.sub.2 n-C.sub.3H.sub.7 CH.sub.2OCH.sub.3 PhCH.sub.2CH.sub.2 i-C.sub.3H.sub.7 CH.sub.2CH.sub.2OCH.sub.3 4-Cl--PhCH.sub.2 n-C.sub.4H.sub.9 CH.sub.2CH.sub.2OCH.sub.2CH.sub.3 COCH.sub.2CO.sub.2CH.s- ub.3 t-C.sub.4H.sub.9 COCH.sub.2OCH.sub.3 COCH.sub.2CH.sub.2CO.sub.2CH.sub.3 ##STR00016## COCH.sub.2OCH.sub.2CH.sub.3 COCHCH.sub.3CO.sub.2CH.sub.3 CH.sub.2Cl CH.sub.2CO.sub.2CH.sub.3 COCH.sub.2COOH CF.sub.3 CH.sub.2CO.sub.2CH.sub.2CH.sub.3 COCH.sub.2CH.sub.2COOH CH.sub.2CF.sub.3 CH.sub.2CH.dbd.CH.sub.2 COCHCH.sub.3COOH COCH.sub.3 CH.sub.2CH.dbd.CF.sub.2 COCH.dbd.CHCOOH COCH.sub.2CH.sub.3 CH.sub.2CH.sub.2CH.dbd.CF.sub.2 COCH.dbd.CHCO.sub.2CH.- sub.3 COCH.sub.2CH.sub.2CH.sub.3 CONHCH.sub.3 CH.sub.2CH.sub.2CF.dbd.CF.sub.2 CH.sub.2CH.dbd.CCl.sub.2 ##STR00017## CONHCH.sub.2CH.sub.3 SO.sub.2CH.sub.3 CH.sub.2C.ident.CH CH.sub.2C.ident.C--I ##STR00018##

TABLE-US-00002 TABLE 2 substitute R.sub.2(R.sub.6) R.sub.2(R.sub.6) R.sub.2(R.sub.6) R.sub.2(R.sub.6) R.sub.2(R.sub.6) H CH.sub.3 OCH(CH.sub.3).sub.2 CH.sub.2CO.sub.2CH.sub.2CH.sub.3 F CH.sub.2CH.sub.3 OCF.sub.3 Ph Cl n-C.sub.3H.sub.7 OCH.sub.2CF.sub.3 CH.sub.2Ph Br i-C.sub.3H.sub.7 OCF.sub.2CF.sub.3 OPh I n-C.sub.4H.sub.9 CH.dbd.CH.sub.2 NHPh CN t-C.sub.4H.sub.9 CH.sub.2CH.dbd.CH.sub.2 COPh NO.sub.2 CF.sub.3 C.ident.CH CO.sub.2Ph COOH CHF.sub.2 CH.sub.2C.ident.CH CO.sub.2Ph-4-Cl CONH.sub.2 CH.sub.2F SO.sub.2CH.sub.3 CO.sub.2Ph-2-Cl-4-CF.sub.3 CONHCH.sub.3 CH.sub.2Cl SO.sub.2CH.sub.2CH.sub.3 CO.sub.2Ph-2-Cl-4-NO.sub.- 2 CON(CH.sub.3).sub.2 CH.sub.2Br COCH.sub.3 CONHPh CONHCH.sub.2CH.sub.3 CH.sub.2CF.sub.3 COCH.sub.2CH.sub.3 CONHPh-4-Cl CON(CH.sub.2CH.sub.3).sub.2 CF.sub.2CHF.sub.2 CO.sub.2CH.sub.3 CONHPh-2-Cl- CONH(CH.sub.2).sub.2CH.sub.3 CF.sub.2CF.sub.3 CO.sub.2CH.sub.2CH.sub.3 CON- HPh-4-NO.sub.2 CONHCH(CH.sub.3).sub.2 OCH.sub.3 CH.sub.2OCH.sub.3 CONHPh-2-Cl-4-CF.sub.3 CONH(CH.sub.2).sub.3CH.sub.3 OCH.sub.2CH.sub.3 CH.sub.2OCH.sub.2CH.sub.3 C- ONHPh-2-Cl-4-NO.sub.2 CONHC(CH.sub.3).sub.3 O(CH.sub.2).sub.2CH.sub.3 CH.sub.2CO.sub.2CH.sub.3 ##STR00019##

TABLE-US-00003 TABLE 3 substitute R.sub.3(R.sub.5) R.sub.3(R.sub.5) R.sub.3(R.sub.5) R.sub.3(R.sub.5) R.sub.3(R.sub.5) H n-C.sub.3H.sub.7 OCH.sub.2CF.sub.3 CH.sub.2Ph F i-C.sub.3H.sub.7 OCF.sub.2CF.sub.3 OPh Cl n-C.sub.4H.sub.9 CH.dbd.CH.sub.2 NHPh Br t-C.sub.4H.sub.9 CH.sub.2CH.dbd.CH.sub.2 COPh I CF.sub.3 C.ident.CH CO.sub.2Ph CN CHF.sub.2 CH.sub.2C.ident.CH CO.sub.2Ph-4-Cl NO.sub.2 CH.sub.2F SO.sub.2CH.sub.3 CO.sub.2Ph-2-Cl-4-CF.sub.3 COOH CH.sub.2Cl SO.sub.2CH.sub.2CH.sub.3 CO.sub.2Ph-2-Cl-4-NO.sub.2 CONH.sub.2 CH.sub.2Br COCH.sub.3 CONHPh CONHCH.sub.3 CH.sub.2CF.sub.3 COCH.sub.2CH.sub.3 CONHPh-4-Cl CON(CH.sub.3).sub.2 CF.sub.2CHF.sub.2 CO.sub.2CH.sub.3 CONHPh-2-Cl CONHCH.sub.2CH.sub.3 CF.sub.2CF.sub.3 CO.sub.2CH.sub.2CH.sub.3 CONHPh-4-NO- .sub.2 CON(CH.sub.2CH.sub.3).sub.2 OCH.sub.3 CH.sub.2OCH.sub.3 CONHPh-2-Cl-4-CF.s- ub.3 CONH(CH.sub.2).sub.2CH.sub.3 OCH.sub.2CH.sub.3 CH.sub.2OCH.sub.2CH.sub.3 C- ONHPh-2-Cl-4-NO.sub.2 CONHCH(CH.sub.3).sub.2 CH.sub.3 CH.sub.2CH.sub.3 O(CH.sub.2).sub.2CH.sub.3 OCH(CH.sub.3).sub.2 OCF.sub.3 CH.sub.2CO.sub.2CH.sub.3 CH.sub.2CO.sub.2CH.sub.2CH.sub.3 Ph ##STR00020##

TABLE-US-00004 TABLE 4 substitute R.sub.4 R.sub.4 R.sub.4 R.sub.4 R.sub.4 H CHF.sub.2 CH.sub.2C.ident.CH CONHCH(CH.sub.3).sub.2 F CH.sub.2F SO.sub.2CH.sub.3 CON(CH.sub.2CH.sub.3).sub.2 Cl CH.sub.2Cl SO.sub.2CH.sub.2CH.sub.3 CONHC(CH.sub.3).sub.3 Br CH.sub.2Br COCH.sub.3 SO.sub.2NH.sub.2 I CH.sub.2CF.sub.3 COCH.sub.2CH.sub.3 SO.sub.2NHCH.sub.3 CN CF.sub.2CHF.sub.2 CO.sub.2CH.sub.3 SO.sub.2N(CH.sub.3).sub.2 NO.sub.2 CF.sub.2CF.sub.3 CO.sub.2CH.sub.2CH.sub.3 Ph COOH OCH.sub.3 CH.sub.2OCH.sub.3 CH.sub.2Ph CO.sub.2Na OCH.sub.2CH.sub.3 CH.sub.2OCH.sub.2CH.sub.3 COPh CO.sub.2NH.sub.4 O(CH.sub.2).sub.2CH.sub.3 CH.sub.2CO.sub.2CH.sub.3 COCH.s- ub.2Ph CH.sub.3 OCH(CH.sub.3).sub.2 CH.sub.2CO.sub.2CH.sub.2CH.sub.3 CO.sub.2Ph CH.sub.2CH.sub.3 OCF.sub.3 OCH.sub.2OCH.sub.3 CO.sub.2Ph-2-Cl-4-CF.sub.3 n-C.sub.3H.sub.7 OCH.sub.2CF.sub.3 OCH.sub.2OCH.sub.2CH.sub.3 CONHPh i-C.sub.3H.sub.7 OCF.sub.2CF.sub.3 CONH.sub.2 CONHPh-4-Cl n-C.sub.4H.sub.9 CH.dbd.CH.sub.2 CONHCH.sub.3 CONHPh-4-CH.sub.3 t-C.sub.4H.sub.9 CH.sub.2CH.dbd.CH.sub.2 CON(CH.sub.3).sub.2 CONHPh-2-Cl-4- -NO.sub.2 CF.sub.3 C.ident.CH CONH(CH.sub.2).sub.2CH.sub.3 CONHPh-2-Cl-4-CF.sub.3

TABLE-US-00005 TABLE 5 substitute R.sub.8(R.sub.10) R.sub.8(R.sub.10) R.sub.8(R.sub.10) R.sub.8(R.sub.10) R.sub.8(R.sub.10) R.- sub.8(R.sub.10) H CH.sub.3 OCH.sub.3 SCH.sub.3 OCOCH.sub.3 F C.sub.2H.sub.5 OCH.sub.2CH.sub.3 SCH.sub.2CH.sub.3 OCOCH.sub.2CH.sub.3 Cl n-C.sub.3H.sub.7 OCF.sub.3 SO.sub.2CH.sub.3 NHCOCH.sub.3 Br i-C.sub.3H.sub.7 OCH.sub.2CF.sub.3 SO.sub.2CH.sub.2CH.sub.3 NHCOCH.sub.- 2CH.sub.3 I n-C.sub.4H.sub.9 NHCH.sub.3 N(CH.sub.3).sub.2 OSO.sub.2CH.sub.3 OH t-C.sub.4H.sub.9 NHCH.sub.2CH.sub.3 N(C.sub.2H.sub.5).sub.2 OSO.sub.2CH- .sub.2CH.sub.3 CN CH.sub.2Cl NH(CH.sub.2).sub.2CH.sub.3 OCH.sub.2CH.dbd.CH.sub.2 OCH.sub.- 2OCH.sub.3 NO.sub.2 CF.sub.3 NHCH(CH.sub.3).sub.2 OCH.sub.2CH.dbd.CCl.sub.2 OCH.sub.2- OCH.sub.2CH.sub.3 COOH CH.sub.2CF.sub.3 NHCH.sub.2CF.sub.3 OCH.sub.2C.ident.CH OCH.sub.2CO.s- ub.2CH.sub.3

The present invention is also explained by the following compounds having general formula II with antitumor activity in Table 6-Table 21, but without being restricted thereby.

##STR00021##

Table 6: In formula II, R.sub.1 is H, R.sub.8 and R.sub.10 are Cl, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 (hereinafter abbreviated to R.sub.2-R.sub.6) are listed in following Table, the numbers of representative compounds are Table 6-1 to Table 6-208.

TABLE-US-00006 TABLE 6 Num- ber R.sub.2 R.sub.3 R.sub.4 R.sub.5 R.sub.6 1 H H H H H 2 F H H H H 3 Cl H H H H 4 Br H H H H 5 I H H H H 6 CH.sub.3 H H H H 7 OCH.sub.3 H H H H 8 NO.sub.2 H H H H 9 CF.sub.3 H H H H 10 CN H H H H 11 H F H H H 12 H Cl H H H 13 H Br H H H 14 H CF.sub.3 H H H 15 H H F H H 16 H H Cl H H 17 H H Br H H 18 H H CH.sub.3 H H 19 H H t-C.sub.4H.sub.9 H H 20 H H OCH.sub.3 H H 21 H H OCF.sub.3 H H 22 H H NO.sub.2 H H 23 H H CN H H 24 H H CF.sub.3 H H 25 H H CO.sub.2CH.sub.3 H H 26 H H SO.sub.2CH.sub.3 H H 27 H H CONHPh H H 28 H H CONHPh-4-CH.sub.3 H H 29 H H CONHPh-4-Cl H H 30 F F H H H 31 F H F H H 32 F H H F H 33 F H H H F 34 F H Cl H H 35 F H H CF.sub.3 H 36 H F F H H 37 H F H F H 38 Cl Cl H H H 39 Cl H Cl H H 40 Cl H H Cl H 41 Cl H H H Cl 42 Cl H H H CH.sub.3 43 H Cl Cl H H 44 H Cl H Cl H 45 Cl H Br H H 46 Br H Cl H H 47 Cl H CF.sub.3 H H 48 Cl H H CF.sub.3 H 49 Cl H NO.sub.2 H H 50 Cl H H NO.sub.2 H 51 Cl H H CN H 52 Cl H H CH.sub.3 H 53 NO.sub.2 H H Cl H 54 CN H H Cl H 55 CH.sub.3 H H Cl H 56 CF.sub.3 H CN H H 57 F H CN H H 58 Cl H CN H H 59 Br H CN H H 60 NO.sub.2 H CN H H 61 t-C.sub.4H.sub.9 H CN H H 62 OCH.sub.3 H CN H H 63 CO.sub.2CH.sub.3 H CN H H 64 SO.sub.2CH.sub.3 H CN H H 65 H F CN H H 66 H Cl CN H H 67 H Br CN H H 68 H NO.sub.2 CN H H 69 H CH.sub.3 CN H H 70 H OCH.sub.3 CN H H 71 CN H Cl H H 72 CF.sub.3 H Cl H H 73 CO.sub.2CH.sub.3 H Cl H H 74 H CN Cl H H 75 H CH.sub.3 Cl H H 76 H CF.sub.3 Cl H H 77 CH.sub.3 H Cl H H 78 CH.sub.3 Cl H H H 79 CH.sub.3 H CH.sub.3 H H 80 CH.sub.3 H H CH.sub.3 H 81 CH.sub.3 H CN H H 82 CH.sub.3 H CF.sub.3 H H 83 CH.sub.3 H CO.sub.2CH.sub.3 H H 84 CH.sub.3 H H H CO.sub.2CH.sub.3 85 H CF.sub.3 CN H H 86 H CH.sub.3 CN H H 87 NO.sub.2 H Cl H H 88 CN H NO.sub.2 H H 89 F F F H H 90 F H F H F 91 F H NO.sub.2 H F 92 Cl Cl Cl H H 93 Cl H Cl H Cl 94 Cl Cl H Cl H 95 Cl H CF.sub.3 H Cl 96 Cl H OCF.sub.3 H Cl 97 Cl H CH.sub.3 H Cl 98 Cl H CN H Cl 99 Cl H NO.sub.2 H Cl 100 Cl H CO.sub.2CH.sub.3 H Cl 101 Cl H SO.sub.2CH.sub.3 H Cl 102 Cl H t-C.sub.4H.sub.9 H Cl 103 Cl H CONHPh H Cl 104 Cl H CONHPh-4-Cl H Cl 105 Cl H CO.sub.2Na H Cl 106 Cl H COOH H Cl 107 Cl H NO.sub.2 H CH.sub.3 108 Cl CH.sub.3 Cl H H 109 Cl H Cl H CN 110 Cl H NO.sub.2 H F 111 Br H OCF.sub.3 H Br 112 Br H Br H Br 113 Br H NO.sub.2 H Cl 114 Br H NO.sub.2 H Br 115 CH.sub.3 H CH.sub.3 H CH.sub.3 116 CH.sub.3 H t-C.sub.4H.sub.9 H CH.sub.3 117 C.sub.2H.sub.5 H Cl H C.sub.2H.sub.5 118 CH.sub.3 H CO.sub.2CH.sub.3 H Br 119 CH.sub.3 H CO.sub.2CH.sub.3 H NO.sub.2 120 CH.sub.3 H CO.sub.2CH.sub.3 H CN 121 CH.sub.3 H CO.sub.2CH.sub.3 H OCH.sub.3 122 CH.sub.3 H CO.sub.2CH.sub.3 H CF.sub.3 123 CH.sub.3 H CO.sub.2CH.sub.3 H Cl 124 CH.sub.3 H Cl H NO.sub.2 125 C.sub.2H.sub.5 H NO.sub.2 H F 126 C.sub.2H.sub.5 H NO.sub.2 H Cl 127 C.sub.2H.sub.5 H NO.sub.2 H Br 128 C.sub.2H.sub.5 H NO.sub.2 H NO.sub.2 129 C.sub.2H.sub.5 H NO.sub.2 H CN 130 C.sub.2H.sub.5 H NO.sub.2 H OCH.sub.3 131 C.sub.2H.sub.5 H NO.sub.2 H CF.sub.3 132 C.sub.2H.sub.5 H NO.sub.2 H CO.sub.2CH.sub.3 133 C.sub.2H.sub.5 H NO.sub.2 H SO.sub.2CH.sub.3 134 C.sub.2H.sub.5 Cl H H C.sub.2H.sub.5 135 Cl H CN H F 136 Cl H CN H Br 137 Cl H CN H NO.sub.2 138 Cl H CN H OCH.sub.3 139 Cl H CN H CO.sub.2CH.sub.3 140 F H CN H Br 141 F H CN H NO.sub.2 142 F H CN H OCH.sub.3 143 F H CN H CO.sub.2CH.sub.3 144 Cl H SO.sub.2NHCH.sub.3 H Cl 145 Cl H SO.sub.2N(CH.sub.3).sub.2 H Cl 146 Cl H CO.sub.2NH.sub.4 H Cl 147 Cl H CONH.sub.2 H Cl 148 Cl H CONHCH.sub.3 H Cl 149 Cl H CON(CH.sub.3).sub.2 H Cl 150 Cl H CONHCH(CH.sub.3).sub.2 H Cl 151 Cl H CONHC(CH.sub.3).sub.3 H Cl 152 CH.sub.3 H Cl CH.sub.3 H 153 NO.sub.2 H Cl H NO.sub.2 154 CN H Cl H NO.sub.2 155 CN H Cl H CH.sub.3 156 CN H Cl H CN 157 CN H Cl H CF.sub.3 158 CO.sub.2CH.sub.3 H Cl H Cl 159 CH.sub.3 H Cl H Cl 160 NO.sub.2 H Cl H Cl 161 CF.sub.3 H Cl H Cl 162 OCH.sub.3 H Cl H Cl 163 NO.sub.2 H Cl H F 164 NO.sub.2 H Cl H Br 165 NO.sub.2 H Cl H CF.sub.3 166 NO.sub.2 H Cl H CO.sub.2CH.sub.3 167 NO.sub.2 H Cl H CH.sub.3 168 CN H NO.sub.2 H NO.sub.2 169 COOH H CN H CH.sub.3 170 COOH H Cl H Cl 171 COOH H Cl H CH.sub.3 172 COOH H Br H CH.sub.3 173 COOH H CN H Cl 174 CO.sub.2CH.sub.3 H Cl H CH.sub.3 175 CO.sub.2CH.sub.3 H Br H CH.sub.3 176 CONHCH.sub.3 H CN H CH.sub.3 177 CONHCH.sub.3 H Cl H Cl 178 CONHCH.sub.3 H Cl H CH.sub.3 179 CONHCH.sub.3 H Br H CH.sub.3 180 CONHCH.sub.3 H H H H 181 CONH.sub.2 H CN H CH.sub.3 182 CONH.sub.2 H Cl H Cl 183 CONH.sub.2 H Cl H CH.sub.3 184 CONH.sub.2 H Br H CH.sub.3 185 CONH.sub.2 H CN H Cl 186 CON(CH.sub.3).sub.2 H CN H CH.sub.3 187 CON(CH.sub.3).sub.2 H Cl H Cl 188 CON(CH.sub.3).sub.2 H Cl H CH.sub.3 189 CON(CH.sub.3).sub.2 H Br H CH.sub.3 190 CON(CH.sub.3).sub.2 H CN H Cl 191 CONHCH(CH.sub.3).sub.2 H CN H CH.sub.3 192 CONHCH(CH.sub.3).sub.2 H Cl H Cl 193 CONHCH(CH.sub.3).sub.2 H Cl H CH.sub.3 194 CONHCH(CH.sub.3).sub.2 H Br H CH.sub.3 195 CONHCH(CH.sub.3).sub.2 H CN H Cl 196 CONHC(CH.sub.3).sub.3 H CN H CH.sub.3 197 CONHC(CH.sub.3).sub.3 H Cl H Cl 198 CONHC(CH.sub.3).sub.3 H Cl H CH.sub.3 199 CONHC(CH.sub.3).sub.3 H Br H CH.sub.3 200 CONHC(CH.sub.3).sub.3 H CN H Cl 201 Cl H Br H Cl 202 Cl H SO.sub.2NH.sub.2 H Cl 203 Cl H SO.sub.2NH.sub.2 H Br 204 Br H SO.sub.2NH.sub.2 H Br 205 Cl CH.sub.3 CN Cl H 206 CH.sub.3 Cl NO.sub.2 H NO.sub.2 207 NO.sub.2 CH.sub.3 Cl H NO.sub.2 208 CN Cl CN Cl Cl

Table 7: In formula II, R.sub.1 is CH.sub.3, R.sub.8 and R.sub.10 are Cl, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 7-1 to Table 7-208.

Table 8: In formula II, R.sub.1 is H, R.sub.8 and R.sub.10 are F, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 8-1 to Table 8-208.

Table 9: In formula II, R.sub.1 is H, R.sub.8 is N(C.sub.2H.sub.5).sub.2, R.sub.10 is Cl, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 9-1 to Table 9-208.

Table 10: In formula II, R.sub.1 is H, R.sub.8 is N(CH.sub.3).sub.2, R.sub.10 is Cl, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 10-1 to Table 10-208.

Table 11: In formula II, R.sub.1 is H, R.sub.8 is NHCH.sub.3, R.sub.10 is Cl, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 11-1 to Table 11-208.

Table 12: In formula II, R.sub.1 is H, R.sub.8 is OCH.sub.3, R.sub.10 is Cl, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 12-1 to Table 12-208.

Table 13: In formula II, R.sub.1 is H, R.sub.8 is SCH.sub.3, R.sub.10 is Cl, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 13-1 to Table 13-208.

Table 14: In formula II, R.sub.1 is H, R.sub.8 and R.sub.10 are OCH.sub.3, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 14-1 to Table 14-208.

Table 15: In formula II, R.sub.1 is H, R.sub.8 and R.sub.10 are N(CH.sub.3).sub.2, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 15-1 to Table 15-208.

Table 16: In formula II, R.sub.1 is H, R.sub.8 and R.sub.10 are NHCH.sub.3, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 16-1 to Table 16-208.

Table 17: In formula II, R.sub.1 is H, R.sub.8 and R.sub.10 are SCH.sub.3, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 17-1 to Table 17-208.

Table 18: In formula II, R.sub.1 is H, R.sub.8 is SO.sub.2CH.sub.3, R.sub.10 is Cl, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 18-1 to Table 18-208.

Table 19: In formula II, R.sub.1 is H, R.sub.8 is OCH.sub.2CH.dbd.CH.sub.2, R.sub.10 is Cl, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 19-1 to Table 19-208.

Table 20: In formula II, R.sub.1 is H, R.sub.8 is OCH.sub.3, R.sub.10 is F, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 20-1 to Table 20-208.

Table 21: In formula II, R.sub.1 is H, R.sub.8 is N(CH.sub.3).sub.2, R.sub.10 is F, R.sub.2-R.sub.6 are listed in Table 6, the number of representative compounds are Table 21-1 to Table 21-208.

The present invention is also explained by the following compounds having general formula III with antitumor activity in Table 22-Table 30, but without being restricted thereby.

##STR00022##

Table 22: In general formula III, R.sub.1 is H, R.sub.8 is Cl, R.sub.9 is NO.sub.2, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 (hereinafter abbreviated to R.sub.2-R.sub.6) are listed in following Table, the numbers of representative compounds are Table 22-1 to Table 22-208.

TABLE-US-00007 TABLE 22 Number R.sub.2 R.sub.3 R.sub.4 R.sub.5 R.sub.6 1 H H H H H 2 F H H H H 3 Cl H H H H 4 Br H H H H 5 I H H H H 6 CH.sub.3 H H H H 7 OCH.sub.3 H H H H 8 NO.sub.2 H H H H 9 CF.sub.3 H H H H 10 CN H H H H 11 CO.sub.2Ph H H H H 12 H F H H H 13 H Cl H H H 14 H Br H H H 15 H CF.sub.3 H H H 16 H H F H H 17 H H Cl H H 18 H H Br H H 19 H H CH.sub.3 H H 20 H H OCH.sub.3 H H 21 H H OCF.sub.3 H H 22 H H NO.sub.2 H H 23 H H CN H H 24 H H CF.sub.3 H H 25 H H CO.sub.2CH.sub.3 H H 26 H H SO.sub.2CH.sub.3 H H 27 H H CONHPh H H 28 H H CONHPh-4-CH.sub.3 H H 29 H H CONHPh-4-Cl H H 30 F F H H H 31 F H F H H 32 F H H F H 33 F H H H F 34 F H Cl H H 35 F H H CF.sub.3 H 36 H F F H H 37 H F H F H 38 Cl Cl H H H 39 Cl H Cl H H 40 Cl H H Cl H 41 Cl H H H Cl 42 Cl H H H CH.sub.3 43 H Cl Cl H H 44 H Cl H Cl H 45 Cl H Br H H 46 Br H Cl H H 47 Cl H CF.sub.3 H H 48 Cl CH.sub.3 H H H 49 Cl H H CF.sub.3 H 50 Cl H NO.sub.2 H H 51 Cl H H NO.sub.2 H 52 Cl H H CN H 53 Cl H H CH.sub.3 H 54 NO.sub.2 H H Cl H 55 CN H H Cl H 56 CH.sub.3 H H Cl H 57 CH.sub.3 H H H Cl 58 CH.sub.3 Cl H H H 59 CF.sub.3 H CN H H 60 F H CN H H 61 Cl H CN H H 62 Br H CN H H 63 NO.sub.2 H CN H H 64 t-C.sub.4H.sub.9 H CN H H 65 OCH.sub.3 H CN H H 66 CO.sub.2CH.sub.3 H CN H H 67 SO.sub.2CH.sub.3 H CN H H 68 H F CN H H 69 H Cl CN H H 70 H Br CN H H 71 H NO.sub.2 CN H H 72 H CH.sub.3 CN H H 73 H OCH.sub.3 CN H H 74 CN H Cl H H 75 CF.sub.3 H Cl H H 76 CO.sub.2CH.sub.3 H Cl H H 77 H CN Cl H H 78 H CH.sub.3 Cl H H 79 H CF.sub.3 Cl H H 80 CH.sub.3 H Cl H H 81 CH.sub.3 H CH.sub.3 H H 82 CH.sub.3 H H CH.sub.3 H 83 CH.sub.3 H CN H H 84 CH.sub.3 H CF.sub.3 H H 85 CH.sub.3 H CO.sub.2CH.sub.3 H H 86 H CF.sub.3 CN H H 87 H CH.sub.3 CN H H 88 NO.sub.2 H Cl H H 89 NO.sub.2 H NO.sub.2 H H 90 CN H NO.sub.2 H H 91 F F F H H 92 F H F H F 93 F H Cl H F 94 F H F H NO.sub.2 95 F H NO.sub.2 H F 96 Cl Cl Cl H H 97 Cl H Cl Cl H 98 Cl H Cl H Cl 99 Cl Cl H Cl H 100 Cl H Br H Cl 101 Cl H CF.sub.3 H Cl 102 Cl H OCF.sub.3 H Cl 103 Cl H CH.sub.3 H Cl 104 Cl H CN H Cl 105 Cl H NO.sub.2 H Cl 106 Cl H NO.sub.2 Cl H 107 Cl H CO.sub.2CH.sub.3 H Cl 108 Cl H SO.sub.2CH.sub.3 H Cl 109 Cl H SO.sub.2NH.sub.2 H Cl 110 Cl H SO.sub.2NH.sub.2 H Br 111 Br H SO.sub.2NH.sub.2 H Br 112 Cl H t-C.sub.4H.sub.9 H Cl 113 Cl H CONHPh H Cl 114 Cl H CONHPh-4-Cl H Cl 115 Cl H CO.sub.2Na H Cl 116 Cl H COOH H Cl 117 Cl H NO.sub.2 H CH.sub.3 118 Cl H NO.sub.2 H NO.sub.2 119 Cl CH.sub.3 Cl H H 120 Cl H Cl H CN 121 Cl H Cl H NO.sub.2 122 Cl H NO.sub.2 H F 123 Cl H NO.sub.2 H Br 124 Cl H OCF.sub.2CHFCF.sub.3 Cl H 125 H Cl ##STR00023## Cl H 126 Br H OCF.sub.3 H Br 127 Br H Br H Br 128 Br H NO.sub.2 H Cl 129 Br H NO.sub.2 H Br 130 Br H NO.sub.2 H CN 131 CH.sub.3 H CH.sub.3 H CH.sub.3 132 CH.sub.3 H t-C.sub.4H.sub.9 H CH.sub.3 133 C.sub.2H.sub.5 H Cl H C.sub.2H.sub.5 134 CH.sub.3 H CO.sub.2CH.sub.3 H Br 135 CH.sub.3 H CO.sub.2CH.sub.3 H NO.sub.2 136 CH.sub.2 H CO.sub.2CH.sub.3 H CN 137 CH.sub.3 H CO.sub.2CH.sub.3 H OCH.sub.3 138 CH.sub.3 H CO.sub.2CH.sub.3 H CF.sub.3 139 CH.sub.3 Cl NO.sub.2 H H 140 CH.sub.3 H NO.sub.2 H Cl 141 C.sub.2H.sub.5 H NO.sub.2 H F 142 C.sub.2H.sub.5 H NO.sub.2 H Cl 143 C.sub.2H.sub.5 H NO.sub.2 H Br 144 C.sub.2H.sub.5 H NO.sub.2 H NO.sub.2 145 C.sub.2H.sub.5 H NO.sub.2 H CN 146 C.sub.2H.sub.5 H NO.sub.2 H OCH.sub.3 147 C.sub.2H.sub.5 H NO.sub.2 H CF.sub.3 148 C.sub.2H.sub.5 H NO.sub.2 H CO.sub.2CH.sub.3 149 C.sub.2H.sub.5 H NO.sub.2 H SO.sub.2CH.sub.3 150 Cl H CF.sub.3 H F 151 Cl H CF.sub.3 H Br 152 Cl H CF.sub.3 H NO.sub.2 153 Cl H CN H NO.sub.2 154 Cl H CF.sub.3 H OCH.sub.3 155 Cl H CF.sub.3 H CO.sub.2CH.sub.3 156 F H CF.sub.3 H Br 157 F H CF.sub.3 H NO.sub.2 158 F H CF.sub.3 H OCH.sub.3 159 F H CF.sub.3 H CO.sub.2CH.sub.3 160 Cl H SO.sub.2NHCH.sub.3 H Cl 161 Cl H SO.sub.2N(CH.sub.3).sub.2 H Cl 162 Cl H CO.sub.2NH.sub.4 H Cl 163 Cl H CONH.sub.2 H Cl 164 Cl H CONHCH.sub.3 H Cl 165 Cl H CON(CH.sub.3).sub.2 H Cl 166 Cl H CONHCH(CH.sub.3).sub.2 H Cl 167 Cl H CONHC(CH.sub.3).sub.3 H Cl 168 CH.sub.3 H Cl H CH.sub.3 169 NO.sub.2 H Cl H NO.sub.2 170 NO.sub.2 H NO.sub.2 H NO.sub.2 171 NO.sub.2 H CF.sub.3 H NO.sub.2 172 NO.sub.2 H CN CF.sub.3 H 173 CN H Cl H NO.sub.2 174 CN H Cl H CH.sub.3 175 CN H Cl H CN 176 CN H Cl H CF.sub.3 177 CO.sub.2CH.sub.3 H Cl H Cl 178 CH.sub.3 H Cl H Cl 179 NO.sub.2 H Cl H Cl 180 NO.sub.2 H Cl Cl H 181 CF.sub.3 H Cl H Cl 182 OCH.sub.3 H Cl H Cl 183 NO.sub.2 H Cl H F 184 NO.sub.2 H Cl H Br 185 NO.sub.2 H Cl H CF.sub.3 186 NO.sub.2 H Cl H CO.sub.2CH.sub.3 187 NO.sub.2 H Cl H CH.sub.3 188 CN H NO.sub.2 H NO.sub.2 189 COOH H CN H CH.sub.3 190 COOH H Cl H Cl 191 COOH H Cl H CH.sub.3 192 COOH H Br H CH.sub.3 193 COOH H CN H Cl 194 CO.sub.2CH.sub.3 H Cl H CH.sub.3 195 CO.sub.2CH.sub.3 H Br H CH.sub.3 196 CONHCH.sub.3 H CN H CH.sub.3 197 CONHCH.sub.3 H Cl H Cl 198 CONHCH.sub.3 H Cl H CH.sub.3 199 CONHCH.sub.3 H Br H CH.sub.3 200 CONHCH.sub.3 H CN H Cl 201 CONH.sub.2 H CN H CH.sub.3 202 CONH.sub.2 H Cl H Cl 203 CONH.sub.2 H Cl H CH.sub.3 204 CONH.sub.2 H Br H CH.sub.3 205 CONH.sub.2 H CN H Cl 206 NO.sub.2 Cl CF.sub.3 H NO.sub.2 207 Cl H NO.sub.2 Cl NO.sub.2 208 Cl H Cl Cl NO.sub.2

Table 23: In formula III, R.sub.1 and R.sub.9 are H, R.sub.8 is Cl, R.sub.2-R.sub.6 are listed in Table 22, the number of representative compounds are Table 23-1 to Table 23-208.

Table 24: In formula III, R.sub.1 is CH.sub.3, R.sub.8 is Cl, R.sub.9 is NO.sub.2, R.sub.2-R.sub.6 are listed in Table 22, the number of representative compounds are Table 24-1 to Table 24-208.

Table 25: In formula III, R.sub.1 is H, R.sub.8 is OCH.sub.3, R.sub.9 is NO.sub.2, R.sub.2-R.sub.6 are listed in Table 22, the number of representative compounds are Table 25-1 to Table 25-208.

Table 26: In formula III, R.sub.1 is H, R.sub.8 is SCH.sub.3, R.sub.9 is NO.sub.2, R.sub.2-R.sub.6 are listed in Table 22, the number of representative compounds are Table 26-1 to Table 26-208.

Table 27: In formula III, R.sub.1 is H, R.sub.8 is NHCH.sub.3, R.sub.9 is NO.sub.2, R.sub.2-R.sub.6 are listed in Table 22, the number of representative compounds are Table 27-1 to Table 27-208.

Table 28: In formula III, R.sub.1 is H, R.sub.8 is N(CH.sub.3).sub.2, R.sub.9 is NO.sub.2, R.sub.2-R.sub.6 are listed in Table 22, the number of representative compounds are Table 28-1 to Table 28-208.

Table 29: In formula III, R.sub.1 is H, R.sub.8 is OCH.sub.2CF.sub.3, R.sub.9 is NO.sub.2, R.sub.2-R.sub.6 are listed in Table 22, the number of representative compounds are Table 29-1 to Table 29-208.

Table 30: In formula III, R.sub.1 and R.sub.8 is H, R.sub.9 is NO.sub.2, R.sub.2-R.sub.6 are listed in Table 22, the number of representative compounds are Table 30-1 to Table 30-208.

The compounds having formula I in present invention have been reported in prior art, which are commercial available or can be prepared according to the following method. The reaction is as follow, wherein the definitions of substituents are as defined above:

##STR00024##

Wherein: X and Y are different, respectively selected from halogen atom or amino; Z is halogen atom; R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are defined respectively as mentioned above; R.sub.1 are defined as mentioned above, but R.sub.1.noteq.H.

According to the above preparation method, treatment of intermediate IV with intermediate V at the presence of base gives compounds I-a of general formula I (R.sub.1.dbd.H), which react with Z--R.sub.1 to give compounds I-b of general formula I (R.sub.1.noteq.H).

The proper base mentioned above may be selected from potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium tert-butoxide or sodium tert-butoxide and so on.

The reaction can be carried out in proper solvent, and the proper solvent mentioned may be selected from tetrahydrofuran, acetonitrile, toluene, xylene, benzene, DMF, N-methylpyrrolidone, DMSO, acetone or butanone and so on.

The proper reaction temperature is from room temperature to boiling point of solvent, generally is 20-100.degree. C.

The reaction time is in the range of 30 minutes to 20 hours, generally is 1-10 hours.

Intermediates IV are commercially available, or prepared according to the known methods, such as referring to Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 45B(4), 972-975, 2006; Tetrahedron Letters, 44(21), 4085-4088, 2003; PL174903, etc.

Intermediate V can be prepared according to the known methods, such as referring to JP2003292476, 052010160695, etc.

The nitration of compounds of general formula I, in which at least one of R.sub.2, R.sub.4, R.sub.6, R.sub.9 or R.sub.11 is H, can add one or several NO.sub.2 groups to these compounds of general formula I.

The halogenation of substituted diphenylamine compounds of general formula I, in which R.sub.2, R.sub.4, R.sub.6, R.sub.7, R.sub.9 or R.sub.11 is not halogen atom, can add one or several halogen atoms to these compounds of general formula I.

The compounds of general formula I, in which R.sub.8 and R.sub.10 are alkylamino, alkoxy or alkylthio, can be prepared from the reaction of compounds of general formula I whose R.sub.8 and R.sub.10 are halogen atom with amine, alcohol or mercaptan (or their salts), or referring to the preparation method in Journal of Medicinal Chemistry, 1978, 21(9), 906-913.

The compounds of general formula I, in which R.sub.8 and R.sub.10 are alkylsulfonyl and alkylcarbonyloxy, can be prepared according to the preparation method in Journal of Medicinal Chemistry, 1978, 21(9), 906-913.

The salts of compounds having general formula I can be prepared from the reaction of the compounds of general formula I with corresponding acid according to routine method. The proper acid may be selected from hydrochloric acid, sulfuric acid, nitric acid, carbonic acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, phenylsulfonic acid, p-toluenesulfonic acid, methylsulfonic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or oxalic acid; The preferred acid are selected from hydrochloric acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, methylsulfonic acid or p-toluenesulfonic acid.

The present invention includes the formulations, which were made from the compounds having the general formula I as active ingredient, and preparation thereof. The preparation of formulations: Dissolve the compounds of present invention in water soluble organic solvents, the ionicity of surfactant, water soluble lipid, all kinds of cyclodextrin, fatty acid, fatty acid ester, phospholipids or their combination solvents, and add physiological saline or 1-20% of carbohydrates. Mentioned organic solvents include polyethylene glycol (PEG), ethanol, propylene glycol or their combination solvents.

The compounds having the general formula I in present invention and their salt and prodrug can be used to prepare the drugs or formulations to cure, prevent or alleviate cancer. The active ingredients are composed of one or more than two diphenylamine compounds having the general formula I. Especially to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The preferred cancers are: colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx cancer or stomach cancer.

The compounds in present invention can be used as active ingredients of antitumor drug, which can be used alone or combined with other antitumorantiviral drugs. The drug combination process in present invention, using at least one of the compounds and its active derivatives with other one or more antitumorantiviral drugs, are used together to increase the overall effect. The dose and drug administration time of combination therapy are based on the most reasonable treatment effect in the different situations.

The formulations include the effective dose of the compounds having general formula I. The "effective dose" refers to the compound dosage, which are effective to cure cancer. The effective dose or dose can be different based on the suggestions of experienced person at different conditions. For instance, the different usage of drug based on different cancers; the dose of drug also can be changed based on whether it shares with other therapeutic method, such as antitumor or antiviral drugs. The drug can be prepared for any useable formulations. The salts of compounds also can be used if the alkaline or acidic compounds can formed the non-toxic acids or salts. The organic acids/salts in pharmacy include anion salts, which are formed with acids, such as p-toluenesulfonic acid, methylsulfonic acid, acetic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or glycerophosphoric acid; the inorganic salts include chloride, bromide, fluoride, iodide, sulfate, nitrate, bicarbonate, carbonate or phosphate. For example, the alkaline compounds, such as amines can form salts with suitable acids; acids can form salts with alkalis or alkaline earth.

The compounds in present invention having general formula I general easily dissolves in organic solvent, water soluble solvent and their mixture with water. The water soluble solvents prefer alcohol, polyethylene glycol, N-methyl-2-pyrrolidone, N,N-dimethyl acetamide, N,N-dimethyl formamide, dimethylsulfoxide, acetonitrile and their mixture. Mentioned alcohols prefer methanol, ethanol, isopropanol, glycerol or ethylene glycol. The compounds in present invention mix with common drug carrier to form formulations. Dissolve the compounds of present invention in water soluble organic solvents, aprotic solvent, water soluble lipid, cyclodextrin, fatty acid, phospholipids or their combination solvents, and add physiological saline or 1-20% of carbohydrates, such as glucose aqueous solution. The stability formulations made by this way are used for animal and clinical.

The drugs were made from the active ingredients of general formula I compounds, which can dose by oral medication or parenteral route, also by implantable medication pump and other methods. Where the parenteral route refer to injection or drip technology through subcutaneous intradermal, intramuscular, intravenous, arteries, atrium, synovium, sternum, intrathecal, wound area, encephalic, etc. The formulations were mixed using conventional method by technicist, which are used for animal and clinical, including tablets, pills, capsule, granule, syrup, injection, freeze-dried powder injection, emulsion, powder, freeze-dried powder, drop pill, milk suspension, aqueous suspension, colloid, colloidal solution, sustained-release suspensions, nanoparticle or other formulations.

The compounds having the general formula I in present invention can be used to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The cancers include but not limited to colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, osteosarcoma, nasopharynx cancer or stomach cancer.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is illustrated by the following examples, but without being restricted thereby. (All raw materials are commercially available unless otherwise specified.)

PREPARATION EXAMPLES

Example 1

Preparation of Compound Table 6-1

##STR00025##

0.35 g (3.76 mmol) of aniline and 0.30 g (7.52 mmol) of sodium hydroxide were added into 40 mL of DMF, and 1.00 g (3.76 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and filtered to give white solid. The solid was washed twice by 30 ml water and twice by 20 ml petroleum ether, 0.65 g of compound Table 6-1 as white solid was obtained, m.p. 226-228.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 7.22 (d, 2H, Ph-2,6-2H, J=7.5 Hz), 7.40-7.46 (m, 3H, Ph-3,4,5-3H).

Example 2

Preparation of Compound Table 6-33

##STR00026##

1.03 g (8 mmol) of 2,6-difluoroaniline and 0.64 g (16 mmol) of sodium hydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/4, as an eluent) to give 1.65 g of compound table 6-33 as yellow solid, m.p. 264-266.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 6.70 (s, 1H, NH), 7.07 (t, 2H, Ph-3,5-2H, J=8.1 Hz), 7.37 (m, 1H, Ph-4-1H).

Example 3

Preparation of Compound Table 6-39

##STR00027##

The preparation is same to compound Table 6-1, brown black solid, m.p. 209-212.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 6.95 (s, 1H, NH), 7.20 (d, 1H, Ph-6-H, J=8.1 Hz), 7.36 (dd, 1H, Ph-5-H, .sup.3J=8.7 Hz, .sup.4J=2.7 Hz), 7.54 (d, 1H, Ph-3-H, J=2.4 Hz).

Example 4

Preparation of Compound Table 6-91

##STR00028##

0.68 g (2 mmol) of compound table 6-33 was dissolved in 20 mL of concentrated sulfuric acid and cooled by ice-bath, the mixed acid (4 mmol of nitric acid and 6 mmol of sulfuric acid) was added dropwise to the reaction solution under stirring to keep the temperature below 20.degree. C. Then the reaction mixture was stirred for another 5 min. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into ice water, extracted with ethyl acetate, the extract was washed by saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/4, as an eluent) to give 0.40 g of compound table 6-91 as white solid, m.p. 204-206.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 6.70 (s, 1H, NH), 7.97-8.01 (dd, 2H, Ph-3,5-2H, .sup.3J=10.8 Hz, .sup.4J=3.0 Hz).

Example 5

Preparation of Compound Table 6-93

##STR00029##

1.57 g (8 mmol) of 2,4,6-trichloroaniline and 0.64 g (16 mmol) of sodium hydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/4, as an eluent) to give 1.91 g of compound table 6-39 as light yellow solid, m.p. 182-184.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 6.86 (s, 1H, NH), 7.48 (s, 2H, Ph-3,5-2H).

Example 6

Preparation of Compound Table 6-99

##STR00030##

0.35 g (1.3 mmol) of 2,6-dichloro-4-nitroaniline and 0.10 g (2.6 mmol) of sodium hydroxide were added into 40 mL of DMF, and 0.27 g (1.3 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/4, as an eluent) to give 0.48 g of compound table 6-99 as yellow solid, m.p. 250-252.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 6.93 (s, 1H, NH), 8.34 (s, 2H, Ph-3,5-2H).

Example 7

Preparation of Compound Table 6-100

##STR00031##

10.33 g (39 mmol) of methyl 4-amino-3,5-dichlorobenzoate (preparation refer to WO2010060379, CN101337940) and 3.12 g (78 mmol) of sodium hydroxide were added into 60 mL of DMF, and 10.37 g (39 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/5, as an eluent) to give 13.65 g of compound table 6-100 as yellow solid, m.p. 229-231.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 3.96 (s, 3H, CH.sub.3), 6.92 (s, 1H, NH), 8.11 (s, 2H, Ph-2,6-2H).

Example 8

Preparation of Compound Table 6-104

##STR00032##

(1) Preparation of Compound Table 6-106

13.31 g (31 mmol) of compound Table 6-100 was dissolved in mixed solution of THF and water (volume ratio=1/1), and 2.45 g (61 mmol) of sodium hydroxide was added to the reaction solution followed by heating for 5 h at 50.degree. C. in oil-bath. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the aqueous phase was acidized by diluted hydrochloric acid, and filtered to give compound Table 6-106 as yellow solid, dried for the next step.

(2) Preparation of Compound Table 6-106a

5.54 g (12.72 mmol) of compound Table 6-106 was added to 100 ml of petroleum ether, and two drops of DMF and 2.27 g (19.08 mmol) of thionyl chloride were added to the reaction solution followed by refluxing for 2 h at 85.degree. C. in oil-bath. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure to obtain compound Table 6-106a.

(3) Preparation of Compound Table 6-104

0.12 g (0.91 mmol) of p-chloroaniline and 0.23 g (2.27 mmol) of triethylamine were dissolved in anhydrous THF, then 0.40 g (0.91 mmol) of compound Table 6-106a was added dropwise to the reaction solution followed by heating for 5 h at 45.degree. C. in oil-bath. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/3, as an eluent) to give 0.23 g of compound table 6-104 as white solid, m.p. 275-276.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 7.31-7.35 (m, 2H, 4-Cl-Ph-2,6-2H), 7.81 (d, 2H, 4-Cl-Ph-3,5-2H, J=9.0 Hz), 8.13 (dd, 2H, Ph-2,6-2H, .sup.3J=15.7 Hz, .sup.4J=1.2 Hz), 10.50 (d, 1H, CONH, J=12.9 Hz).

Example 9

Preparation of Compound Table 6-112

##STR00033##

2.63 g (8 mmol) of 2,4,6-trichloroaniline and 0.64 g (16 mmol) of sodium hydroxide were added into 40 mL of DMF, and 2.13 g (8 mmol) of 2,4,5,6-tetrachloroisophthalonitrile was added slowly under stirring, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/4, as an eluent) to give 3.22 g of compound table 6-112 as brown solid, m.p. 238-239.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 6.86 (s, 1H, NH), 7.48 (s, 2H, Ph-3,5-2H).

Example 10

Preparation of Compound Table 14-99

##STR00034##

0.55 g (1.3 mmol) of compound Table 6-99 and 0.14 g (2.5 mmol) of sodium methoxide were dissolved in 20 ml of DMSO, followed by heating for 8 h at 95.degree. C. in oil-bath. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into water, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/4, as an eluent) to give 0.16 g of compound table 14-99 as yellow solid, m.p. 151-153.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 4.23 (t, 6H, OCH.sub.3, J=6.6 Hz), 6.78 (br, 1H, NH), 8.31 (d, 2H, Ph-3,5-2H, J=3.9 Hz).

Example 11

Preparation of Compound Table 22-39

##STR00035##

0.81 g (0.005 mol) of 2,4-dichloroaniline was added in portions to a suspension of 0.4 g (0.01 mol) of NaH (60%) and 20 mL of THF, the mixture was stirred for 30 min after addition, 1.56 g (0.006 mol) of 2,6-dichloro-3,5-dinitrotulune in 30 mL of THF was added within 30 min, then stirred for another 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was filtered. The filtrate was concentrated under reduced pressure, then the residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/20, as an eluent) to give 1.37 g of compound table 22-39 as yellow solid, m.p. 136-137.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 2.14 (s, 3H), 6.53 (d, 1H), 7.17 (d, 1H), 7.49 (s, 1H), 8.68 (s, 1H), 8.93 (s, 1H).

Example 12

Preparation of Compound Table 22-101

##STR00036##

The preparation is same to compound Table 22-39, m.p. 143-144.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 1.98 (s, 3H), 7.66 (s, 2H), 8.70 (s, 1H), 9.10 (s, 1H).

Example 13

Preparation of Compound Table 22-105

##STR00037##

0.83 g (0.004 mol) of 2,6-dichloro-4-nitroaniline was added in portions to a suspension of 0.32 g (0.008 mol) of NaH (60%) and 10 mL of DMF, the mixture was stirred for 30 min after addition, 1.20 g (0.0048 mol) of 2,6-dichloro-3,5-dinitrotulune was added in portions within 30 min, then stirred for another 3 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into 50 mL of saturated brine and extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/10, as an eluent) to give 1.20 g of compound table 22-105 as yellow solid, m.p. 157-158.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 2.02 (s, 3H), 8.29 (s, 2H), 8.65 (s, 1H), 8.95 (s, 1H).

Example 14

Preparation of Compound Table 22-120

##STR00038##

The preparation is same to compound Table 22-39, m.p. 148-150.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 2.07 (s, 3H), 7.53 (s, 1H), 7.72 (s, 1H), 8.71 (s, 1H), 8.97 (s, 1H).

Example 15

Preparation of Compound Table 22-121

##STR00039##

0.56 g (0.0015 mol) of compound table 22-39 was dissolved in 5 mL of concentrated sulfuric acid (96%, the same below) and cooled to 0.degree. C., 0.15 g of fuming nitric acid (95%) and 3 mL of concentrated sulfuric acid was mixed evenly and added to the flask, then the reaction mixture was stirred for another 5 min. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into ice water, the solid precipitated was filtered, and the filter mass was washed with water and dried to give 0.59 g of compound table 22-121 as brown solid, m.p. 156-158.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 2.09 (s, 3H), 7.66 (s, 1H), 8.01 (s, 1H), 8.60 (s, 1H), 9.75 (s, 1H).

Example 16

Preparation of Compound Table 22-153

##STR00040##

The preparation is same to compound Table 22-39, m.p. 204-206.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 2.23 (s, 3H), 7.87 (s, 1H), 8.38 (s, 1H), 8.51 (s, 1H), 10.00 (s, 1H).

Example 17

Preparation of Compound Table 22-206

##STR00041##

The intermediate M prepared by the procedure of Example 13 was nitrated according to Example 2 to give compound Table 22-206 as reddish-brown solid, m.p. 136-138.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 2.41 (s, 3H), 8.50 (s, 1H), 8.72 (s, 1H), 10.10 (s, 1H).

Example 18

Preparation of Compound Table 24-39

##STR00042##

0.38 g (0.001 mol) of compound table 22-39 was added to a suspension of 0.10 g (0.0025 mol) of NaH (60%) and 10 mL of DMF, the mixture was stirred for 1 h and then added thereto 0.43 g (0.003 mol) of CH.sub.3I, the resulting mixture was allowed to react for 5 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into 50 mL of saturated brine and extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/10, as an eluent) to give 0.15 g of compound table 22-39 as yellow solid, m.p. 142-144.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 2.54 (s, 3H), 3.31 (s, 3H), 7.09 (d, 1H), 7.25 (d, 2H), 8.04 (s, 1H).

Example 19

Preparation of Compound Table 27-105

##STR00043##

0.42 g of compound table 22-105 (0.001 mol) was added to a microwave vial and dissolved with 2.5 mL of DMSO, 1 mL of methylamine aqueous solution (25%) was added, the vial was lidded and put into the microwave reactor, then the reaction was carried out at 150.degree. C. for 40 min. The reaction mixture was poured into 50 mL of saturated brine and extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=120, as an eluent) to give 0.25 g of compound table 27-105 as yellow solid, m.p. 218-219.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 1.70 (s, 3H), 3.09 (d, 3H), 8.25 (d, 1H), 8.31 (s, 2H), 9.12 (s, 1H), 9.58 (s, 1H).

Example 20

Preparation of Compound Table 29-105

##STR00044##

0.42 g (1 mmol) of compound Table 22-105 and 2 mmol of sodium 2,2,2-trifluoroethanolate (made from trifluoroethanol and sodium) were dissolved in 3 ml of DMSO, heating to 150.degree. C. for 10 min in microwave synthesizer (Biotage). Then the reaction mixture was poured into saturated brine, and extracted with ethyl acetate, the extract was washed by water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=120, as an eluent) to give 0.21 g of compound table 29-105 as yellow solid, m.p. 126-128.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 1.83 (s, 3H), 4.42 (q, 2H), 8.30 (s, 2H), 8.85 (s, 1H), 9.20 (s, 1H).

Example 21

Preparation of Compound Table 30-105

##STR00045##

0.83 g (0.004 mol) of 2,6-dichloro-4-nitroaniline was added in portions to a suspension of 0.32 g (0.008 mol) of NaH (60%) and 10 mL of DMF, the mixture was stirred for 30 min after addition, 1.04 g (0.0048 mol) of 2-chloro-1-methyl-3,5-dinitrobenzene was added in portions within 30 min, then stirred for another 3 h. After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was poured into 50 mL of saturated brine and extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90.degree. C.)=1/10, as an eluent) to give 0.96 g of compound Table 30-105 as yellow solid, m.p. 146-148.degree. C.

.sup.1H-NMR spectrum (300 MHz, internal standard: TMS, solvent CDC.sub.3) .delta.(ppm): 1.96 (s, 3H), 8.26 (d, 1H), 8.29 (s, 2H), 8.95 (d, 1H), 9.00 (s, 1H).

Other compounds of the present invention were prepared according to the above examples.

Physical properties and .sup.1HNMR spectrum (.sup.1HNMR, 300 MHz, internal standard: TMS, ppm) of some compounds of this invention are as follows:

TABLE-US-00008 Table Compound Mp. (.degree. C.) and .sup.1HNMR (300 MHz, internal standard: TMS, solvent No. No. CDCl.sub.3) 6 3 m.p. 208-210.degree. C. .delta. (CDCl.sub.3): 7.03 (s, 1H, NH), 7.27-7.38 (m, 3H, Ph-3,5,6-3H), 7.49-7.55 (m, 1H, Ph-4-H). 6 6 m.p. 212-214.degree. C. .delta. (CDCl.sub.3): 2.29 (s, 3H, CH.sub.3), 7.00 (s, 1H, NH), 7.15 (d, H, Ph-6-H, J = 7.5 Hz), 7.28-7.34 (m, 3H, Ph-3,4,5-3H). 6 10 m.p. 258-260.degree. C. .delta. (CDCl.sub.3): 7.12 (s, 1H, NH), 7.24 (d, 1H, Ph-6-H, J = 7.5 Hz), 7.47 (t, 1H, Ph-4-H, J = 7.2 Hz), 7.68 (t, 1H, Ph-5-H, J = 7.5 Hz), 7.78 (d, 1H, Ph-3-H, J = 7.8 Hz). 6 14 m.p. 236-238.degree. C. .delta. (CDCl.sub.3): 7.12 (s, 1H, NH), 7.28-7.40 (m, 1H, Ph-6-H), 7.41-7.52 (m, 2H, Ph-2,4-2H), 7.54-7.62 (m, 1H, Ph-5-H). 6 19 m.p. 144-146.degree. C. .delta. (CDCl.sub.3): 1.30 (s, 9H, t-C.sub.4H.sub.9), 6.65 (m, 2H, Ph-2,6-2H), 7.16 (s, 1H, NH), 7.18 (m, 2H, Ph-3,5-2H). 6 21 m.p. 204-206.degree. C. .delta. (CDCl.sub.3): 7.09 (s, 1H, NH), 7.22-7.32 (m, 4H, Ph-2,3,5,6-4H). 6 23 m.p. 259-261.degree. C. .delta. (CDCl.sub.3): 7.00 (s, 1H, NH), 7.17 (d, 2H, Ph-2,6-2H, J = 8.7 Hz), 7.42 (d, 2H, Ph-3,5-2H, J = 9.0 Hz). 6 25 m.p. 246-248.degree. C. .delta. (CDCl.sub.3): 2.29 (s, 3H, COOCH.sub.3), 7.08 (s, 1H, NH), 7.17 (d, 2H, Ph-3,5-2H, J = 8.7 Hz), 8.10 (d, 2H, Ph-2,6-2H, J = 8.7 Hz). 6 31 m.p. 206-208.degree. C. .delta. (CDCl.sub.3): 6.88 (s, 1H, NH), 6.99 (t, 2H, Ph-5,6-2H, J = 8.1 Hz), 7.32 (d, 1H, Ph-3-H, J = 2.4 Hz). 6 35 m.p. 209-212.degree. C. 6.93 (s, 1H, NH), 7.34 (t, 1H, Ph-3-H, J = 9.0 Hz), 7.52 (d, 1H, Ph-4-H, J = 7.2 Hz), 7.58-7.65 (m, 1H, Ph-3-H). 6 38 m.p. 218-220.degree. C. .delta. (CDCl.sub.3): 7.03 (s, 1H, NH), 7.13 (dd, 1H, Ph-6-H, .sup.3J = 8.1 Hz, .sup.4J = 0.9 Hz), 7.28 (t, 1H, Ph-5-H, J = 8.1 Hz), 7.47 (dd, 1H, Ph-4-H, .sup.3J = 8.1 Hz, .sup.4J = 0.9 Hz). 6 41 m.p. 235-237.degree. C. .delta. (CDCl.sub.3): 6.61 (s, 1H, NH), 7.36 (t, 1H, Ph-4-H, J = 7.2 Hz), 7.45 (d, 2H, Ph-3,5-2H, J = 7.2 Hz). 6 42 m.p. 240-242.degree. C. .delta. (CDCl.sub.3): 2.32 (s, 3H, Ph--CH.sub.3), 6.93 (s, 1H, NH), 7.22-7.35 (m, 3H, Ph-3,4,5-H). 6 44 m.p. 238-242.degree. C. .delta. (CDCl.sub.3): 6.95 (s, 1H, NH), 7.05 (d, 2H, Ph-2,6-2H, J = 1.8 Hz), 7.32 (d, 1H, Ph-4-H, J = 1.5 Hz). 6 47 m.p. 166-168.degree. C. .delta. (CDCl.sub.3): 7.00 (s, 1H, NH), 7.20 (d, 1H, Ph-6-H, J = 8.4 Hz), 7.57 (dd, 1H, Ph-5-H, .sup.3J = 8.4 Hz, .sup.4J = 1.5 Hz), 7.78 (s, 1H, Ph-3-H). 6 48 m.p. 197-199.degree. C. .delta. (CDCl.sub.3): 7.02 (s, 1H, NH), 7.45 (s, 1H, Ph-6-H), 7.55 (d, 1H, Ph-4-H, J = 8.4 Hz), 7.65 (d, 1H, Ph-3-H, J = 8.4 Hz). 6 49 m.p. 220-222.degree. C. 7.04 (d, 1H, Ph-6-H, J = 8.7 Hz), 7.07 (s, 1H, NH), 8.20 (dd, 1H, Ph-5-H, .sup.3J = 9.0 Hz, .sup.4J = 2.7 Hz), 8.42 (d, 1H, Ph-3-H, J = 2.7 Hz). 6 77 m.p. 200-202.degree. C. .delta. (CDCl.sub.3): 2.27 (s, 3H, Ph-2-CH.sub.3), 6.86 (s, 1H, NH), 7.07 (d, 1H, Ph-6-H, J = 8.4 Hz), 7.23 (dd, 1H, Ph-5-H, .sup.3J = 8.4 Hz, .sup.4J = 2.1 Hz), 7.33 (s, 1H, Ph-3-H). 6 78 m.p. 140-142.degree. C. .delta. (CDCl.sub.3): 2.35 (s, 3H, CH.sub.3), 6.99 (s, 1H, NH), 7.08 (d, 1H, Ph-6-H, J = 8.1 Hz), 7.19-7.25 (m, 1H, Ph-5-H), 7.46 (d, 1H, Ph-4-H, J = 8.7 Hz). 6 80 m.p. 198-200.degree. C. .delta. (CDCl.sub.3): 2.23 (s, 3H, CH.sub.3), 2.34 (s, 3H, CH.sub.3), 6.95 (s, 1H, NH), 6.95 (s, 1H, Ph-6-H), 7.13-7.22 (m, 2H, Ph-3,4-2H). 6 83 m.p. 204-205.degree. C. .delta. (CDCl.sub.3): 2.36 (s, 3H, COOCH.sub.3), 3.92 (s, 3H, Ph-3-CH.sub.3), 6.85 (s, 1H, NH), 7.12 (d, 1H, Ph-5-1H, J = 8.4 Hz), 7.92 (d, 1H, Ph-6-1H, J = 8.4 Hz), 8.02 (s, 1H, Ph-2-1H). 6 84 m.p. 216-218.degree. C. .delta. (CDCl.sub.3): 2.16 (s, 3H, CH.sub.3), 3.89 (s, 3H, COOCH.sub.3), 7.39 (t, 1H, Ph-4-H, J = 7.8 Hz), 7.51 (d, 1H, Ph-5-H, J = 7.8 Hz), 7.93 (d, 1H, Ph-3-H, J = 7.8 Hz). 6 85 m.p. 242-243.degree. C. .delta. (CDCl.sub.3): 7.07 (s, 1H, NH), 7.25 (d, 1H, Ph-6-H, J = 2.1 Hz), 7.42 (d, 1H, Ph-2-H, J = 2.4 Hz), 7.83 (d, 1H, Ph-5-H, J = 8.4 Hz). 6 87 m.p. 232-234.degree. C. .delta. (CDCl.sub.3): 6.94 (d, 1H, Ph-6-H, J = 9.3 Hz), 7.58 (dd, 1H, Ph-5-H, .sup.3J = 9.0 Hz, .sup.4J = 2.7 Hz), 8.26 (d, 1H, Ph-3-H, J = 2.7 Hz), 9.36 (s, 1H, NH). 6 88 m.p. 236-238.degree. C. .delta. (DMSO): 7.02 (dd, 1H, Ph-6-H, .sup.3J = 9.6 Hz, .sup.4J = 2.7 Hz), 8.32 (dd, 1H, Ph-5-H, .sup.3J = 9.3 Hz, .sup.4J = 2.7 Hz), 8.63 (d, 1H, Ph-3-H, J = 2.7 Hz). 6 95 m.p. 201-203.degree. C. .delta. (CDCl.sub.3): 6.91 (s, 1H, NH), 7.72 (s, 2H, Ph-3,5-2H). 6 98 m.p. 259-261.degree. C. .delta. (CDCl.sub.3): 6.91 (s, 1H, NH), 7.74 (s, 2H, Ph-3,5-2H). 6 103 m.p. 267-269.degree. C. .delta. (CDCl.sub.3): 7.28-7.30 (m, 1H, NHPh-4-H), 7.40 t, 2H, NHPh-3,5-2H, J = 6.9 Hz), .delta. = 7.62 (d, 2H, NHPh-2,6-2H, J = 7.8 Hz), .delta. = 7.89-7.95 (m, 2H, NHCOPh-2,6-2H). 6 107 m.p. 232-234.degree. C. .delta. (CDCl.sub.3): 2.43 (s, 3H, Ph--CH.sub.3), 6.86 (s, 1H, NH), 8.14 (s, 1H, Ph-5-1H), 8.26 (s, 1H, Ph-3-1H). 6 108 m.p. 196-198.degree. C. .delta. (CDCl.sub.3): 2.55 (s, 3H, CH.sub.3), 6.99 (s, 1H, NH), 7.04 (d, 1H, Ph-6-H, J = 8.4 Hz), 7.36 (d, 1H, Ph-5-H, J = 8.4 Hz). 6 109 m.p. 194-196.degree. C. .delta. (CDCl.sub.3): 6.96 (s, 1H, NH), 7.67 (d, 1H, Ph-5-H, J = 2.1 Hz), 7.77 (d, 1H, Ph-3-H, J = 2.4 Hz). 6 110 m.p. 197-199.degree. C. 6.86 (s, 1H, NH), 8.05 (dd, 1H, Ph-5-H, .sup.3J = 9.9 Hz, .sup.4J = 2.7 Hz), 8.28 (d, 1H, Ph-3-H, J = 2.4 Hz). 6 113 m.p. 248-250.degree. C. .delta. (CDCl.sub.3): 6.95 (s, 1H, NH), 8.37 (d, 1H, Ph-3-H, J = 2.7 Hz), 8.49 (d, 1H, Ph-5-H, J = 2.4 Hz). 6 114 m.p. 247-249.degree. C. .delta. (CDCl.sub.3): 6.96 (s, 1H, NH), 8.51 (s, 2H, Ph-3,5-2H). 6 134 m.p. 176-178.degree. C. .delta. (CDCl.sub.3): 1.15-1.27 (m, 6H, CH.sub.3), 2.49 (q, 4H, CH.sub.2, J = 7.5 Hz), 6.98 (s, 1H, NH), 7.14 (d, 1H, Ph-5-H, J = 8.4 Hz), 7.47 (d, 1H, Ph-3-H, J = 8.4 Hz). 6 152 m.p. 222-223.degree. C. .delta. (CDCl.sub.3): 2.22 (s, 3H, CH.sub.3), 2.34 (s, 3H, CH.sub.3), 6.88 (s, 1H, NH), 7.00 (s, 1H, Ph-6-H), 7.30 (s, 1H, Ph-3-H). 6 176 m.p. 260-262.degree. C. .delta. (CDCl.sub.3): 2.06 (s, 3H, CH.sub.3), 2.98 (d, 3H, NHCH.sub.3, J = 4.8 Hz), 6.38 (s, 1H, CONH), 7.67 (s, 2H, Ph-3,5-2H), 9.38 (s, 1H, NH). 6 178 m.p. 240-242.degree. C. .delta. (CDCl.sub.3): 2.08 (s, 3H, CH.sub.3), 2.93 (d, 3H, NCH.sub.3, J = 5.1 Hz), 6.22 (s, 1H, CONH), 7.35-7.38 (m, 2H, Ph-3,5-2H), 8.59 (s, 1H, NH). 6 180 m.p. 180-182.degree. C. .delta. (CDCl.sub.3): 2.69 (s, 3H, CH.sub.3), 7.12 (s, 1H, NH), 7.24-7.68 (m, 4H, Ph). 6 206 m.p. 156-158.degree. C. .delta. (CDCl.sub.3): 2.51 (s, 3H, CH.sub.3), 8.67 (s, 1H, Ph), 8.89 (s, 1H, NH). 9 8 Yellow oil. .delta. (CDCl.sub.3): 1.13-1.21 (m, 6H, CH.sub.3), 3.46 (q, 4H, CH.sub.2, J = 7.2 Hz), 6.90 (s, 1H, NH), 7.13 (t, 2H, Ph-2,6-2H, J = 7.5 Hz), 7.31 (d, 1H, Ph-4-H, J = 7.5 Hz), 7.42 (t, 2H, Ph-3,5-2H, J = 7.2 Hz). 10 99 m.p. 127-129.degree. C. .delta. (CDCl.sub.3): 3.22 (s, 6H, CH.sub.3), 6.85 (s, 1H, NH), 8.32 (s, 2H, Ph-3,5-2H). 12 99 m.p. 198-200.degree. C. .delta. (CDCl.sub.3): 4.25 (s, 3H, CH.sub.3), 6.87 (s, 1H, NH), 8.32 (s, 2H, Ph-3,5-2H). 14 4 m.p. 142-144.degree. C. .delta. (CDCl.sub.3): 4.14 (s, 3H, OCH.sub.3), 4.17 (t, 3H, OCH.sub.3, J = 4.2 Hz), 6.91 (s, 1H, Ph--NH--Ph), 7.18 (d, 2H, Ph-2,6-2H, J = 7.8 Hz), 7.32 (t, 1H, Ph-4-H, J = 7.2 Hz), 7.42 (t, 2H, Ph-3,5-2H, J = 7.5 Hz). 16 2 m.p. 176-178.degree. C. .delta. (CDCl.sub.3): 3.26 (d, 3H, NCH.sub.3, J = 8.7 Hz), 3.37 (d, 3H, NCH.sub.3 J = 8.1 Hz), 5.04 (br, 1H, Ph--NH--C), 5.26 (br, 1H, Ph--NH--C), 6.35 (s, 1H, Ph--NH--Ph), 7.04 (d, 2H, Ph-2,6-2H, J = 8.1 Hz), 7.14 (t, 1H, Ph-4-H, J = 7.2 Hz), 7.35 (t, 2H, Ph-3,5-2H, J = 7.5 Hz). 22 11 m.p. 158-160.degree. C. .delta. (CDCl.sub.3): 2.10 (s, 3H), 6.83 (d, 4H), 7.12 (m, 2H), 7.34 (m, 4H), 8.56 (s, 1H). 22 22 m.p. 172-174.degree. C. .delta. (DMSO): 2.34 (s, 3H), 6.83 (d, 2H), 8.06 (d, 2H), 8.64 (s, 1H), 9.49 (s, 1H). 22 23 m.p. 184-186.degree. C. .delta. (CDCl.sub.3): 2.22 (s, 3H), 6.87 (d, 2H), 7.62 (d, 2H), 8.66 (s, 1H), 8.93 (s, 1H). 22 24 m.p. 91-94.degree. C. .delta. (CDCl.sub.3): 2.14 (s, 3H), 6.91 (d, 2H), 7.21 (d, 2H), 8.71 (s, 1H), 9.20 (s, 1H). 22 31 m.p. 136-138.degree. C. .delta. (CDCl.sub.3): 2.12 (s, 3H), 7.21 (m, 2H), 7.26 (m, 1H), 8.72 (s, 1H), 9.00 (s, 1H). 22 47 m.p. 106-108.degree. C. .delta. (CDCl.sub.3): 2.22 (s, 3H), 6.55 (d, 1H), 7.43 (d, 1H), 7.75 (s, 1H), 8.65 (s, 1H), 8.87 (s, 1H). 22 48 m.p. 110-112.degree. C. .delta. (CDCl.sub.3): 2.03 (s, 3H), 2.50 (s, 3H), 6.50 (d, 1H), 7.05 (t, 1H), 7.24 (d, 1H), 8.73 (s, 1H), 9.06 (s, 1H). 22 50 m.p. 191-193.degree. C. .delta. (CDCl.sub.3): 2.29 (s, 3H), 6.48 (d, 1H), 8.06 (d, 1H), 8.41 (s, 1H), 8.62 (s, 1H), 8.79 (s, 1H). 22 56 m.p. 146-148.degree. C. .delta. (CDCl.sub.3): 1.86 (s, 3H), 2.40 (s, 3H), 7.18 (m, 2H), 7.28 (m, 1H), 8.80 (s, 1H), 9.52 (s, 1H). 22 58 m.p. 133-135.degree. C. .delta. (CDCl.sub.3): 2.03 (s, 3H), 2.50 (s, 3H), 6.53 (d, 1H), 7.06 (t, 1H), 7.21 (d, 1H), 8.74 (s, 1H), 9.08 (s, 1H). 22 61 m.p. 206-208.degree. C. .delta. (CDCl.sub.3): 2.25 (s, 3H), 6.48 (d, 1H), 7.47 (d, 1H), 7.77 (s, 1H), 8.62 (s, 1H), 8.80 (s, 1H). 22 63 m.p. 259-261.degree. C. .delta. (CDCl.sub.3): 2.38 (s, 3H), 6.54 (d, 1H), 7.70 (d, 1H), 8.50 (s, 1H), 8.62 (s, 1H), 10.51 (s, 1H). 22 80 m.p. 121-123.degree. C. .delta. (CDCl.sub.3): 2.02 (s, 3H), 2.40 (s, 3H), 6.53 (d, 1H), 7.10 (d, 1H), 7.27 (s, 1H), 8.74 (s, 1H), 9.03 (s, 1H). 22 86 oil. .delta. (DMSO): 2.33 (s, 3H), 6.92 (d, 1H), 7.26 (s, 1H), 7.78 (d, 1H), 8.63 (s, 1H), 9.54 (s, 1H). 22 88 m.p. 204-205.degree. C. .delta. (CDCl.sub.3): 2.31 (s, 3H), 6.48 (d, 1H), 7.43 (d, 1H), 8.26 (s, 1H), 8.54 (s, 1H), 10.36 (s, 1H). 22 89 m.p. 185-186.degree. C. .delta. (CDCl.sub.3): 2.41 (s, 3H), 6.56 (d, 1H), 8.31 (d, 1H), 8.52 (s, 1H), 9.23 (s, 1H), 10.59 (s, 1H). 22 93 m.p. 148-150.degree. C. .delta. (CDCl.sub.3): 2.12 (s, 3H), 7.04 (d, 2H), 8.70 (s, 1H), 8.87 (s, 1H). 22 94 m.p. 154-156.degree. C. .delta. (CDCl.sub.3): 2.21 (s, 3H), 7.20 (m, 1H), 7.80 (m, 1H), 8.59 (s, 1H), 9.94 (s, 1H). 22 95 m.p. 140-142.degree. C. .delta. (CDCl.sub.3): 2.17 (s, 3H), 7.19 (d, 2H), 8.71 (s, 1H), 8.94 (s, 1H). 22 97 m.p. 142-143.degree. C. .delta. (CDCl.sub.3): 2.20 (s, 3H), 6.59 (s, 1H), 7.58 (s, 1H), 8.67 (s, 1H), 8.80 (s, 1H). 22 98 m.p. 160-162.degree. C. .delta. (CDCl.sub.3): 1.95 (s, 3H), 7.41 (s, 2H), 8.72 (s, 1H), 9.19 (s, 1H). 22 104 m.p. 180-182.degree. C. .delta. (CDCl.sub.3): 1.99 (s, 3H), 7.69 (s, 2H), 8.67 (s, 1H), 9.00 (s, 1H). 22 106 m.p. 169-171.degree. C. .delta. (CDCl.sub.3): 2.32 (s, 3H), 6.42 (s, 1H), 8.20 (s, 1H), 8.60 (s, 1H), 8.62 (s, 1H). 22 107 m.p. 132-134.degree. C. .delta. (CDCl.sub.3): 1.95 (s, 3H), 3.96 (s, 3H), 8.05 (s, 2H), 8.70 (s, 1H), 9.13 (s, 1H). 22 116 m.p. 216-219.degree. C. .delta. (CDCl.sub.3): 2.30 (s, 3H), 7.88 (s, 2H), 8.48 (s, 1H), 8.85 (s, 1H). 22 118 m.p. 169-171.degree. C. .delta. (CDCl.sub.3): 2.26 (s, 3H), 8.50 (d, 2H), 8.99 (s,

1H), 10.14 (s, 1H). 22 119 m.p. 160-161.degree. C. .delta. (CDCl.sub.3): 2.13 (s, 3H), 2.54 (s, 3H), 6.40 (d, 1H), 7.19 (d, 1H), 8.68 (s, 1H), 8.96 (s, 1H). 22 122 m.p. 135-137.degree. C. .delta. (CDCl.sub.3): 2.16 (s, 3H), 7.95 (dd, 1H), 8.26 (t, 1H), 8.63 (s, 1H), 8.82 (s, 1H). 22 123 m.p. 151-153.degree. C. .delta. (CDCl.sub.3): 1.99 (s, 3H), 8.31 (d, 1H), 8.47 (d, 1H), 8.66 (s, 1H), 9.00 (s, 1H). 22 124 m.p. 96-97.degree. C. .delta. (CDCl.sub.3): 2.21 (s, 3H), 5.08 (m, 1H), 6.59 (s, 1H), 7.49 (s, 1H), 8.66 (s, 1H), 8.78 (s, 1H). 22 125 m.p. 192-194.degree. C. .delta. (CDCl.sub.3): 2.20 (s, 3H), 7.05 (s, 2H), 8.04 (s, 1H), 8.22 (s, 1H), 9.07 (s, 1H), 9.43 (s, 1H). 22 126 m.p. 125-127.degree. C. .delta. (CDCl.sub.3): 1.94 (s, 3H), 7.53 (s, 2H), 8.75 (s, 1H), 9.29 (s, 1H). 22 129 m.p. 151-154.degree. C. .delta. (CDCl.sub.3): 1.97 (s, 3H), 8.49 (s, 2H), 8.68 (s, 1H), 9.03 (s, 1H). 22 130 m.p. 172-175.degree. C. .delta. (DMSO): 2.32 (s, 3H), 8.49 (s, 1H), 8.68 (s, 2H), 9.50 (s, 1H). 22 133 m.p. 131-132.degree. C. .delta. (CDCl.sub.3): 2.10 (s, 3H), 6.99 (t, 2H), 7.17 (m, 1H), 8.72 (s, 1H), 8.98 (s, 1H). 22 139 m.p. 158-161.degree. C. .delta. (CDCl.sub.3): 2.16 (s, 3H), 2.61 (s, 3H), 6.47 (d, 1H), 7.67 (d, 1H), 8.69 (s, 1H), 8.85 (s, 1H). 22 140 m.p. 137-139.degree. C. .delta. (CDCl.sub.3): 1.91 (s, 3H), 2.31 (s, 3H), 8.10 (s, 1H), 8.21 (s, 1H), 8.73 (s, 1H), 9.20 (s, 1H). 22 152 m.p. 160-162.degree. C. .delta. (CDCl.sub.3): 2.18 (s, 3H), 7.88 (d, 1H), 8.32 (d, 1H), 8.55 (s, 1H), 9.97 (s, 1H). 22 163 m.p. 241-243.degree. C. .delta. (CDCl.sub.3): 1.97 (s, 3H), 7.83 (s, 2H), 8.69 (s, 1H), 9.11 (s, 1H). 22 164 .delta. (CDCl.sub.3): 1.94 (s, 3H), 3.03 (d, 3H), 7.78 (s, 2H), 8.70 (s, 1H), 9.14 (s, 1H). 22 169 m.p. 187-190.degree. C. .delta. (CDCl.sub.3): 2.18 (s, 3H), 8.23 (s, 2H), 8.57 (s, 1H), 10.39 (s, 1H). 22 170 oil. .delta. (CDCl.sub.3): 2.27 (s, 3H), 8.52 (s, 1H), 9.09 (s, 2H), 10.93 (s, 1H). 22 171 m.p. 93-95.degree. C. .delta. (CDCl.sub.3): 2.19 (s, 3H), 8.14 (s, 2H), 8.56 (s, 1H), 10.42 (s, 1H). 22 172 m.p. 204-206.degree. C. .delta. (DMSO): 2.32 (s, 3H), 7.03 (s, 1H), 8.73 (s, 1H), 8.86 (s, 1H), 10.40 (s, 1H). 22 180 m.p. 127-129.degree. C. .delta. (CDCl.sub.3): 2.36 (s, 3H), 6.55 (s, 1H), 8.40 (s, 1H), 8.54 (s, 1H), 10.31 (s, 1H). 22 207 m.p. 159-162.degree. C. .delta. (CDCl.sub.3): 2.16 (s, 3H), 8.23 (s, 1H), 8.63 (s, 1H), 8.91 (s, 1H). 22 208 m.p. 133-135.degree. C. .delta. (CDCl.sub.3): 2.07 (s, 3H), 7.70 (s, 1H), 8.69 (s, 1H), 9.22 (s, 1H). 23 22 m.p. 136-138.degree. C. .delta. (CDCl.sub.3): 2.22 (s, 3H), 6.70 (d, 2H), 7.41 (d, 1H), 8.00 (d, 1H), 8.16 (d, 2H), 8.22 (s, 1H). 23 23 m.p. 146-148.degree. C. .delta. (CDCl.sub.3): 2.19 (s, 3H), 6.70 (d, 2H), 7.36 (d, 1H), 7.53 (d, 2H), 7.96 (d, 1H), 8.20 (s, 1H). 23 24 m.p. 72-74.degree. C. .delta. (CDCl.sub.3): 2.12 (s, 3H), 6.75 (d, 2H), 7.12 (d, 2H), 7.25 (d, 1H), 7.98 (d, 1H), 8.46 (s, 1H). 23 63 m.p. 158-160.degree. C. .delta. (CDCl.sub.3): 2.30 (s, 3H), 6.47 (d, 1H), 7.59 (m, 2H), 7.94 (d, 1H), 8.60 (s, 1H), 10.21 (s, 1H). 23 77 m.p. 136-138.degree. C. .delta. (CDCl.sub.3): 2.22 (s, 3H), 6.75 (d, 1H), 7.03(s, 1H), 7.45 (d, 1H), 7.67 (d, 1H), 7.99 (d, 1H), 8.16 (s, 1H). 23 80 oil. .delta. (CDCl.sub.3): 2.02 (s, 3H), 2.38 (s, 3H), 6.34 (d, 1H), 7.00 (d, 1H), 7.18 (m, 2H), 7.98 (d, 1H), 8.30 (s, 1H). 23 97 m.p. 112-114.degree. C. .delta. (CDCl.sub.3): 2.18 (s, 3H), 6.38 (s, 1H), 7.38 (d, 1H), 7.50 (s, 1H), 7.97 (d, 1H), 8.11 (s, 1H). 23 101 oil. .delta. (CDCl.sub.3): 1.92 (s, 3H), 7.22 (d, 1H), 7.58 (s, 2H), 7.93 (d, 1H), 8.39 (s, 1H). 24 47 m.p. 138-140.degree. C. .delta. (CDCl.sub.3): 2.58 (s, 3H), 3.37 (s, 3H), 7.23 (d, 1H), 7.48 (s, 1H), 7.57 (d, 1H), 8.08 (s, 1H). 24 170 m.p. 140-142.degree. C. .delta. (CDCl.sub.3): 2.58 (s, 3H), 3.30 (s, 3H), 8.38 (s, 1H), 8.57 (s, 2H). 25 105 m.p. 134-136.degree. C. .delta. (CDCl.sub.3): 1.79 (s, 3H), 3.96 (s, 3H), 8.29 (s, 2H), 8.74 (s, 1H), 9.18 (s, 1H). 26 105 m.p. 132-134.degree. C. .delta. (CDCl.sub.3): 2.11 (s, 3H), 2.39 (s, 3H), 8.29 (s, 2H), 8.47 (s, 1H), 8.95 (s, 1H). 27 164 m.p. 216-218.degree. C. .delta. (CDCl.sub.3): 1.56 (s, 3H), 3.04 (m, 6H), 7.80 (s, 2H), 8.18 (s, 1H), 9.13 (s, 1H), 9.58 (s, 1H). 28 105 m.p. 178-180.degree. C. .delta. (CDCl.sub.3): 1.71 (s, 3H), 2.86 (s, 6H), 8.29 (s, 2H), 8.66 (s, 1H), 9.45 (s, 1H). 30 101 m.p. 155-157.degree. C. .delta. (CDCl.sub.3): 1.90 (s, 3H), 7.66 (s, 2H), 8.21 (s, 1H), 8.98 (s, 1H), 9.19 (s, 1H). 30 104 m.p. 183-185.degree. C. .delta. (CDCl.sub.3): 1.93 (s, 3H), 7.68 (s, 2H), 8.23 (d, 1H), 8.94 (d, 1H), 9.03 (s, 1H). 30 120 m.p. 175-177.degree. C. .delta. (CDCl.sub.3): 2.00 (s, 3H), 7.54 (d, 1H), 7.71 (d, 1H), 8.28 (d, 1H), 8.96 (d, 1H), 9.02 (s, 1H). 30 122 m.p. 108-110.degree. C. .delta. (CDCl.sub.3): 2.11 (s, 3H), 7.95 (dd, 1H), 8.26 (d, 1H), 8.31 (d, 1H), 8.79 (s, 1H), 8.92 (d, 1H).

Cell Viability Assay

Example 22

In Vitro Cell Inhibition Assay (MTT Method)

The human cancer cell lines used for this assay were lung cancer A549 and leukemia HL-60.

The concentrations of compounds used for this assay were 0.01, 0.1, 1, 10, 100 .mu.M. Based on in vitro cell culture, we use the MTT assay to detect the inhibitory rate of each compound.

The A549 or HL-60 cells were picked up from cell incubator, after washed for twice using PBS, cells were digested by 0.25% trypsin, and then add medium to terminate the digestion. After cells were collected using centrifuge and re-suspended, count cells under inverted microscope and add medium to make a density was 5.times.10.sup.4 cells/mL. After 100 .mu.L aliquots were added to each well of 96-well microtiter plates, cells were cultured in 5% incubator for overnight at 37.degree. C., then the different concentration compounds were added to each well. After incubation for 48 h, MTT solution was added to each well and plates were then incubated for 4 h. The MTT tetrazolium was reduced to formazan by living cells. Then the formazan crystals were dissolved though adding DMSO to each well. The absorbance was read at 570 nm with a microplate reader.

Part of the test results are as follows:

TABLE-US-00009 TABLE 31 Proliferation inhibitory effect of the compounds on A549 cell (% of Control) Compounds Concentration (.mu.M) No. 100 10 1 0.1 0.01 6-1 19.8 20.4 16.9 12.1 13.1 6-23 93.8 93.7 2.5 -1.8 -0.8 6-35 92.7 58.6 1.0 -0.8 0.5 6-39 92.6 24.9 19.6 18.8 18.3 6-41 92.0 84.0 13.1 0.7 3.8 6-93 98.2 80.3 74.8 39.4 12.1 6-98 93.2 90.1 11.7 -0.7 -2.5 6-99 86.3 83.6 55.0 0 0 6-113 93.7 75.6 2.6 2.9 9.2 6-114 94.9 82.1 11.5 2.8 10.1 22-33 90.3 78.7 61.3 -1.1 -1.6 22-93 91.4 73.7 -0.2 -1.8 -2.2 22-101 97.5 66.4 19.1 21.4 13.7 22-105 89.8 80.6 49.9 8.8 16 22-120 92.1 86.8 9.8 0 0.8 22-121 89.5 51.2 9.9 12.4 6.2 22-153 85.2 60.6 14.7 0 3.7 22-208 91.3 83.2 2.4 -1.2 -1.0 25-105 93.7 78.0 0.9 2.2 3.1 28-105 89.6 54.9 2.7 5.3 4.1 29-105 91.9 94.2 72.7 -0.5 -0.2 30-104 91.8 78.4 -0.1 1.1 2.4 30-120 92.0 84.0 -0.7 -0.9 -1.5

TABLE-US-00010 TABLE 32 Proliferation inhibitory effect of the compounds on HL-60 cells (% of Control) Compounds Concentration (.mu.M) No. 100 10 1 0.1 0.01 6-1 61.9 63.9 18.8 10.4 11.5 6-3 94.5 72.2 -2.1 -6.3 -7.1 6-10 77.1 78.5 9.8 16.1 21.8 6-23 90.6 93.2 23.1 10.8 2.3 6-35 89.9 72.3 -1.8 -5.0 -8.3 6-39 80.8 78.5 31.0 14.7 11.9 6-41 87.9 86.5 7.8 3.9 6.5 6-93 74.8 72.3 70.7 51.8 0 6-98 95.1 91.7 30.0 10.1 -2.5 6-99 54.8 56.5 60.2 34.2 8.6 6-109 94.4 52.4 2.9 2.2 0.1 6-113 93.1 85.4 9.3 8.8 -3.8 6-114 93.2 87.5 20.7 10.0 -0.4 6-205 91.9 59.5 5.8 12.6 -3.4 22-24 94.3 82.4 -9.3 -16.7 -22.4 22-33 81.2 66.2 54.3 -1.8 -4.9 22-61 89.8 85.7 11.0 7.8 5.2 22-88 94.1 79.1 -24.6 -32.9 -35.2 22-93 95.4 70.4 6.8 -7.1 -3.6 22-95 95.4 76.0 32.6 -4.0 0.3 22-98 91.0 77.7 9.5 1.3 -7.3 22-101 64.7 73.4 48.6 5.5 8.3 22-104 94.0 60.5 -2.1 -7.3 4.1 22-105 53.8 70.4 71.1 31.7 27.2 22-107 94.4 65.4 -7.0 -9.3 2.8 22-120 61.0 63.1 19.7 20.5 9.6 22-121 61.2 73.6 47.6 12.5 13 22-122 94.6 57.2 11.7 -1.9 6.3 22-153 65.8 73.4 59.6 7.3 12.9 22-207 90.5 61.9 0.4 -3.6 7.3 22-208 91.2 91.2 28.9 -14.0 -8.0 25-105 88.0 80.2 20.0 4.4 3.1 26-105 88.0 80.2 20.0 4.4 3.1 28-105 77.2 88.4 13.3 -3.7 4.9 29-105 91.5 95.1 94.7 70.2 11.2 30-101 80.7 57.3 -0.3 -14.2 -6.4 30-104 93.3 88.0 65.3 31.6 21.8 30-105 89.0 85.6 80.6 43.6 -6.8 30-120 95.7 95.9 70.6 39.2 23.6 30-122 82.4 61.3 18.0 7.4 10.7

Example 23

In Vitro Cell Inhibition Assay Using the Cell Counting Kit-8(CCK-8) Method

The human cancer cell lines used for this assay were: non-small cell lung cancer A549, NCI-H1650 and NCI-H358, leukemia HL-60, CCRF-CEM and MOLT-4, colon cancer HT-29 and COLO-205, pancreatic cancer BXPC-3, hepatocarcinoma SK-HEP-1, cervical cancer Hela, bladder cancer T24, prostate cancer DU-145 and PC-3, osteosarcoma MG-63, breast cancer MDA-MB-231, intracranial malignant melanoma A375, glioma U251, nasopharyngeal carcinoma CNE.

The concentrations of compounds used for this assay were 0.01, 0.1, 1, 10, 100 .mu.M. Based on in vitro cell culture, we use the CCK-8 assay to detect the inhibitory rate of each compound.

The non-small cell lung cancer A549, NCI-H1650 and NCI-H358, colon cancer HT-29 and COLO-205, pancreatic cancer BXPC-3, hepatocarcinoma SK-HEP-1, cervical cancer Hela, bladder cancer T24, prostate cancer DU-145 and PC-3, osteosarcoma MG-63, breast cancer MDA-MB-231, intracranial malignant melanoma A375, glioma U251, nasopharyngeal carcinoma CNE were picked up from cell incubator. After the cell culture flasks gently shaking, culture fluid was discarded in clean bench. Then washed cells for twice using PBS, and add 0.25% trypsin to digest, when the cells were turning round, add medium to terminate digestion. Cells were collected and transferred to centrifuge tube. For the non-adherent cells HL-60, CCRF-CEM and MOLT-4, cell flasks were picked up from incubator and then transferred to the centrifuge tubes directly. After cells were collected using centrifuge at 1000 rpm/min for 5 min, the fluid was discarded. Then cells were washed for one time by PBS, discard fluid. Then add some medium, count cells under inverted microscope using blood cell counting plate, according the counting number to making the density of adherent cell was 1.times.10.sup.5 cells/mL, the non-adherent cell was 2.times.10.sup.5 cells/mL (the volumes of HL-60, CCRF-CEM, MOLT-4 are smaller than non-adherent cells, these cells added to each well was much more higher). Add 50 .mu.L aliquots to each well of 96-well plates (the density of adherent cells was 5000 cells/well, non-adherent cells was 10000 cells/well). Blank control, Negative control, blank control with compounds and positive control wells were grouped, and three replicate wells were used for each data point in the experiments. Then the cells were cultured in 5% incubator for overnight at 37.degree. C., Then the different concentration compounds were added to each well. After incubation for 48 h, according to the manufacturer's instructions, CCK-8 reagent (10 .mu.l) was added and incubation was continued for a further 2-4 h. The absorbance (A) of each well was read at 450 nm using a plate reader.

TABLE-US-00011 TABLE 33 Proliferation inhibitory effect of the compounds on A549 cells (% of Control) Compounds Concentration (.mu.M) No. 100 10 1 0.1 0.01 6-24 87.36 60.31 31.44 24.27 22.06 6-25 81.32 55.87 17.11 18.59 15.66 6-47 99.91 55.57 53.58 49.86 42.56 6-93 98.18 87.64 70.04 19.35 14.77 6-95 98.69 97.88 78.63 56.27 39.65 6-100 89.94 57.45 52.15 50.53 43.98 6-111 99.83 80.03 53.14 29.42 23.15 6-112 99.26 89.34 76.90 47.20 46.52 6-201 83.86 60.23 26.90 19.63 14.31

TABLE-US-00012 TABLE 34 Proliferation inhibitory effect of the compounds on HL-60 cells (% of Control) Compounds Concentration (.mu.M) No. 100 10 1 0.1 0.01 6-24 95.11 56.72 48.39 17.55 0.00 6-25 84.30 92.02 84.06 42.54 11.52 6-43 78.53 73.80 38.45 31.60 23.65 6-45 80.30 52.09 39.89 27.78 0.00 6-47 98.51 83.33 41.47 34.70 7.02 6-93 93.71 87.80 82.05 44.96 30.19 6-95 96.40 94.99 94.76 43.28 0.00 6-100 97.42 49.85 39.47 26.90 14.24 6-111 99.28 95.16 79.31 41.52 13.70 6-112 96.45 97.63 91.55 59.46 48.31 6-201 98.14 86.76 75.70 48.61 40.59

TABLE-US-00013 TABLE 35 The half maximal inhibitory concentration (IC50) of the compounds Compound6- Tumor cells Cell culture 93 Gefitinib Taxol Non-small-cell A549 0.715 33.688 83.528 carcinoma NCI-H1650 1.366 16.260 0.420 NCI-H358 0.443 1.166 0.278 leukemia HL-60 0.085 34.445 <0.01 CCRF-CEM <0.01 12.691 <0.01 MOLT-4 0.167 25.839 <0.01 Colorectal Cancer HT-29 0.224 18.310 >100 COLO-205 0.125 6.973 <0.01 Prostate cancer DU-145 0.646 3.371 17.428 PC-3 1.356 77.363 69.019 cervical cancer Hela 1.509 35.442 <0.01 bladder cancer T24 0.603 31.346 3.535 nasopharyngeal CNE 6.078 43.682 >100 glioma U251 1.616 26.801 >100 pancreatic cancer BXPC-3 0.331 24.011 <0.01 hepatocarcinoma SK-HEP-1 0.489 9.074 0.047 breast cancer MDA-MB-231 0.175 >100 2.018 melanoma A375 0.160 35.463 55.345 osteosarcoma MG-63 0.196 33.706 <0.01