Concentrations of one or more carbohydrates phosphorylated at a secondary hydroxyl, including fructose-3-phosphate and sorbitol-3-phosphate, in biological tissue or cells of diabetic patients are determined by .sup.31 P NMR Spectroscopy, High Performance Liquid Chromatography (HPLC) or other appropriate analytical techniques. Elevated levels of such phosphorylated carbohydrates, relative to a prescribed standard or threshold level, are associated with an increased risk for developing the degenerative complications of diabetes. A method is provided for determining the relative concentrations of such phosphorylated carbohydrates, whereby the relative risk of a patient for the development of diabetic complications and the efficacy of therapeutic intervention in prevention of such complications may be assessed.

Fox Chase Cancer Center

Method for assessing risk of diabetes-associated pathologic conditions and efficacy of therapies for such conditions

The present invention provides pyrazole derivatives represented by the general formula: ##STR00001## wherein R.sup.1 represents H, an optionally substituted C.sub.1-6 alkyl, etc.; one of Q and T represents a group selected from the following: ##STR00002## and the other represents -Z-Ar wherein Z represents --O--, --S--, etc.; Ar represents an optionally substituted C.sub.6-10 aryl, etc.; R represents an optionally substituted C.sub.3-8 cycloalkyl, an optionally substituted C.sub.6-10 aryl, etc., pharmaceutically acceptable salts thereof, and prodrugs thereof, which exhibit an excellent inhibitory activity in human sodium/glucose cotransporter (SGLT) and are useful as agents for the prevention, inhibition of progression or treatment of a disease associated with the excess uptake of at least a kind of carbohydrates selected from glucose, fructose and mannose (diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications, etc.), and pharmaceutical compositions containing the same, medicinal uses thereof and intermediates for production therefor.

Kissei Pharmaceutical Co., Ltd.

Pyrazole derivative, drug composition containing the same and production intermediate therefor

The present invention provides pyrazole derivatives represented by the general formula: ##STR00001## wherein R.sup.1 represents H, an optionally substituted C.sub.1-6 alkyl group etc.; one of Q and T represents a group selected from the following groups: ##STR00002## and the other represents --(CH.sub.2).sub.n--Ar wherein Ar represents an optionally substituted C.sub.6-10 aryl group or an optionally substituted C.sub.1-9 heteroaryl group; and n represents an integral number from 0 to 2, an optionally substituted C.sub.1-6 alkoxyl group, an optionally substituted amino group, an optionally substituted C.sub.2-9 heterocycloalkyl group or an optionally substituted heterocycle-fused phenyl group; R represents an optionally substituted C.sub.3-8 cycloalkyl group, an optionally substituted C.sub.6-10 aryl group etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human 1,5-anhydroglucitol/fructose/mannose transporter and are useful as agents for the prevention, inhibition of progression or treatment of a disease associated with the excess uptake of at least a kind of carbohydrates selected from glucose, fructose and mannose or a disease associated with hyperglycemia (e.g., diabetic complications, diabetes, etc.), and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.

diabetes complications/carbohydrate

Method for assessing risk of diabetes-associated pathologic conditions and efficacy of therapies for such conditions

Pyrazole derivative, drug composition containing the same and production intermediate therefor

Pyrazole derivative, medicinal composition containing the same, medicinal use thereof and intermediate in producing the same

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