Tetrahydropyranochromene gamma secretase inhibitors

US8664411B2 · kind B2 · utility

Assignee

• Merck Sharp & Dohme LLC · US

Inventors

• Wen-Lian Wu · Edison, US
• Thomas Bara · Linden, US
• Duane A. Burnett · Wayland, US
• John W. Clader · Cranford, US
• Martin S. Domalski · Verona, US
• Yan Jin · Princeton, US
• Hubert Josien · Hoboken, US
• Hongmei Li · Hackettstown, US
• Xian Liang · Moorestown, US
• Dmitri Pissarnitski · Scotch Plains, US
• Thavalakulamgara K. Sasikumar · Westfield, US
• Jesse K. Wong · Union, US
• Ruo Xu · Watchung, US
• Zhiqiang Zhao · Scotch Plains, US
• Paul E. McNamara · Scotch Plains, US

Key dates

• Filing date: Jul 1, 2008
• Grant date: Mar 4, 2014
• Expiry date: Nov 25, 2029

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D407/12
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)—O—C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)—O—C(O)-heteroaryl and a basic tertiary amine.