Synthesis and use of -ketoamide derivatives and arrays

• Main Authors: Baldino, Carmen M, Coffen, David L, Chipman, Stewart D, Cheng, Hong
• Format: Patent
• Language: English
• Published: 17.09.2002

The invention relates to non-peptidic -ketoamide compounds and molecular arrays of potential protease inhibitors and the uses thereof. The invention is based on new methods for making and using compounds and arrays of novel -ketoamides, and the arrays and compounds made by these methods. These novel compounds are potential inhibitors of proteolytic enzymes, particularly cysteine proteases such as cruzain. Application of the new methods has led to the identification of a number of new inhibitors, from amongst an array of about 38,000 -ketoamide derivatives, having specific activity against three cysteine proteases: cruzain, papain, and cathepsin B. These compounds and other compounds identified by the methods described herein can be useful, for example, in developing pharmaceutical agents for the treatment of diseases (e.g., Chagas' disease) associated with these proteases. Although the disclosed compounds have specific activity for cruzain, papain, cathepsin B, the methods described herein can also be used to identify inhibitors of other proteases.