Schering Corporation

Merck Sharp + Dohme Corp.

Pharmacopeia Inc.

Thavalakulamgara K Sasikumar

Duane A Burnett

Wen-Lian Wu

Li Qiang

Martin Domalski

Hubert B Josien

Jing Su

Hongmei Li

Ruo Xu

William J Greenlee

John W Clader

Deen Tulshian

Dmitri A Pissarnitski

Theodros Asberom

Haiqun Tang

Zhiqiang Zhao

Lisa S Silverman

Julius J Matasi

Thomas A Bara

Peter Korakas

Brian Alexander McKittrick

Chad E Bennett

Chad E Knutson

Mary Ann Caplen

Mark D McBriar

Murali Rajagopalan

David James Cole

Zhaoning Zhu

Tao Guo

Jesse K Wong

Yuanzan C Ye

Rachael Catherine Hunter

Paul E McNamara

Robert Mazzola

Xian Liang

Mary Anne Caplen

Yan Jin

Martin S Domalski

Paul Mcnamara

Rachael Hunter

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)&#x2014;O&#x2014;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)&#x2014;O&#x2014;C(O)-heteroaryl and a basic tertiary amine. 

Tetrahydropyranochromene gamma secretase inhibitors

Disclosed are novel gamma secretase inhibitors of the formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, wherein L, n, X, Ar, Y, Z, Q, and Qare as defined herein. Also disclosed are methods for inhibiting gamma secretase, methods for treating Alzheimer's disease, methods of treating one or more neurodegenerative diseases, and methods of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain) using the compounds of formula 1.0. 

Benzenesulfonyl-chromane, thiochromane, tetrahydronaphthalene and related gamma secretase inhibitors

This invention discloses novel gamma secretase inhibitors of the formula: Rand R, or Rand R, or Rand R, together with the atoms to which they are bound, can form a fused cycloalkyl or fused heterocycloalkyl ring. The cycloalkyl ring or the heterocycloalkyl ring can be optionally substituted with one or more substituents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

This invention discloses novel gamma secretase inhibitors of the formula: Rand R, or Rand R, or Rand R, together with the atoms to which they are bound, can form a fused cycloalkyl or fused heterocycloalkyl ring. The cycloalkyl ring or the heterocycloalkyl ring can be optionally substituted with one or more substitutents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

In its many embodiments, the present invention provides tricyclic compounds of formula I (wherein J-J, X, and R-Rare as defined herein) useful as metabotropic glutamate receptor (mGluR) antagonists, particularly as selective metabotropic glutamate receptor 1 antagonists, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases associated with metabotropic glutamate receptor (e.g., mGluR1) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimer's disease. 

mGluR1 antagonists as therapeutic agents

The present invention discloses compounds of formula I wherein Ar, Y, m, n, Rand Rare herein defined, said compounds being novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

2-substituted benzimidazole piperidines analogs as selective melanin concentrating hormone receptor antagonists for the treatment of obesity and related disorders

The present invention provides compounds, which, are novel antagonists for D/Dreceptors as well as methods for preparing such compounds. In another embodiment, the invention provides pharmaceutical compositions comprising such D/Dreceptor antagonists as well as methods of using them to treat CNS disorders, obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

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The present invention discloses compounds which are novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In other aspects, the invention is directed to pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes. Compounds of the invention generally have the structure: where the substituents are as defined herein.

Biaryltetrahydroisoquinoline piperidines as selective MCH receptor antagonists for the treatment of obesity and related disorders

In its many embodiments, the present invention provides tricyclic compounds of formula I (wherein J-J, X, and R&#x2014;Rare as defined herein) useful as metabotropic glutamate receptor (mGluR) antagonists, particularly as selective metabotropic glutamate receptor 1 antagonists, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases associated with metabotropic glutamate receptor (e.g., mGluR1) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimer's disease. 

The present invention discloses compounds of formula I wherein m, n, p, R, Rand X, are herein defined, the compounds being novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

Heterocyclyls as selective melanin concentrating hormone receptor antagonists for the treatment of obesity and related disorders

Selective D1/D5 receptor antagonists for the treatment of obesity and CNS disorders

The present invention discloses compounds which, are novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

Spirosubstituted piperidines as selective melanin concentrating hormone receptor antagonists for the treatment of obesity

The present invention discloses compounds of formula Iwherein Ar, Z, m, n, p, Rand Rare herein defined, said compounds being novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

Aminobenzimidazoles as selective melanin concentrating hormone receptor antagonists for the treatment of obesity and related disorders

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Edison, NJ, United States of America

Thavalakulamgara K Sasikumar