Heterocyclic aspartyl protease inhibitors

US8691831B2 · kind B2 · utility

Assignees

• Merck Sharp & Dohme LLC · US
• Pharmacopeia Drug Discovery, Inc. · US

Inventors

• Zhaoning Zhu · Plainsboro, US
• Brian McKittrick · New Vernon, US
• Zhong-Yue Sun · Sayreville, US
• Yuanzan C. Ye · New Brunswick, US
• Johannes H. Voight · Cranford, US
• Corey Strickland · Bound Brook, US
• Elizabeth M. Smith · Verona, US
• Andrew Stamford · Madison, US
• William J. Greenlee · Teaneck, US
• Robert Mazzola · Stewartsville, US
• John P. Caldwell · Ringwood, US
• Jared N. Cumming · Garwood, US
• Lingyan Wang · East Brunswick Township, US
• Yusheng Wu · New York, US
• Ulrich Iserloh · Hoboken, US
• Xiaoxiang Liu · River Vale, US
• Tao Guo
• Thuy X. E. Le · Monmouth Junction, US
• Kurt W. Saionz · Cranford, US
• Suresh D. Babu · Pennington, US
• Rachael C. Hunter · Princeton, US
• Michelle L. Morris · Lawrenceville, US
• Huizhong Gu · Monmouth Junction, US
• Gang Qian · Kendall Park, US
• Dawit Tadesse · Avenel, US
• Ying Huang · Berkeley Heights, US
• Guoqing Li · Montgomery, US
• Jianping Pan · Monmouth Junction, US
• Jeffrey A. Misiaszek · Kenilworth, US
• Gaifa Lai · Edison, US

Key dates

• Filing date: Mar 9, 2012
• Grant date: Apr 8, 2014
• Expiry date: May 6, 2032

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K31/4178
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed are compounds of the formula Ior a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula I are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.