Compounds of the following backbone structure: ##STR00001## which are useful as Tumor necrosis factor (TNF) inhibitors in treating disease related to elevated TNF.

Aventis Pharma Limited

Imidazolyl-cyclic acetals

The present invention is directed to a process for the preparation of a compound of formula (X-a) ##STR1##or a pharmaceutically acceptable salt form thereof,wherein: R.sup.1 is selected from the group consisting of: C.sub.1-5 alkyl substituted with 0-5 R.sup.1a, --(CH.sub.2).sub.r --C.sub.3-10 cycloalkyl substituted with 0-5 R.sup.1a, and --(CH.sub.2).sub.r -aryl substituted with 0-5 R.sup.1a.Compounds of Formula (X-a) are macrocyclic molecules containing anti-succinate residues which inhibit metalloproteinases such as aggrecanase, and the production of tumor necrosis factor (TNF). The anti-succinates are formed by an Ireland Claisen rearrangement of a silyl ketene acetal which proceeds with high stereoselectivity.

Process for the preparation of macrocyclic metalloprotease inhibitors

The present invention is directed to a process for the preparation of a compound of formula (X-a): ##STR1##or a pharmaceutically acceptable salt form thereof, wherein:R.sup.1 is selected from the group consisting of:C.sub.1-5 alkyl substituted with 0-5 R.sup.1a, --(CH.sub.2).sub.r --C.sub.3-10 cycloalkyl substituted with 0-5 R.sup.1a, and --(CH.sub.2).sub.r -aryl substituted with 0-5 R.sup.1a.Compounds of Formula (X-a) are macrocyclic molecules containing anti-succinate residues which inhibit metalloproteinases such as aggrecanase, and the production of tumor necrosis factor (TNF). The anti-succinates are formed by an Ireland Claisen rearrangement of a silyl ketene acetal which proceeds with high stereoselectivity.

acetal/vefjadrep

Imidazolyl-cyclic acetals

Process for the preparation of macrocyclic metalloprotease inhibitors

Process for the preparation of macrocyclic metalloprotease inhibitors

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