Process for the synthesis of substituted gamma lactams

摘要

The present invention provides synthetic processes for the preparation of a variety of well-defined substituted gamma lactams. The compounds that can be prepared by the process of the invention are useful for treating a variety of conditions. In some embodiments of the invention, the compounds are useful for treating ocular disorders, such as, for example, glaucoma, lowering of elevated intraocular pressure, and the like. In other embodiments, the compounds are useful for treating irritable bowel disease. In further embodiments, the compounds are useful in promoting hair growth. In still further embodiments, the compounds are useful in promoting wound healing, scar reduction, and the like.

主权项

1. A process for preparing a compound having the general structure (1) wherein:
R1 is H, C1-C6 alkyl, or hydroxyethyl;R2 is C1-C10 alkyl;Ar is C5-C10 arylene or heteroarylene; andm and n are each independently 1-6;comprising:a) reacting compound (2) wherein p is 0 to 5;with an alcohol having the structure R1—OH under suitable esterifying conditions to provide compound (3)(b) coupling compound (3) with compound (5) wherein Z is a protecting group,under suitable conditions to provide compound (6)(c) subjecting compound (6) to sufficient reducing conditions to provide compound (7)(d) coupling compound (7) with compound (8)under suitable conditions to provide compound (9)wherein R3, R4 and R5 are each independently C1-C4 straight or branched chain alkyl; and(e) subjecting compound (9) to acidifying conditions,thereby providing a compound of general structure (1).