Schering Corporation

Merck Sharp + Dohme Corp.

Martin Domalski

Duane A Burnett

Wen-Lian Wu

Thavalakulamgara K Sasikumar

Li Qiang

Hubert B Josien

Dmitri A Pissarnitski

Zhiqiang Zhao

John W Clader

Deen Tulshian

Hongmei Li

Ruo Xu

Lisa S Silverman

Thomas A Bara

Julius J Matasi

David James Cole

Peter Korakas

Jing Su

Theodros Asberom

Haiqun Tang

Chad E Bennett

Chad E Knutson

Mary Ann Caplen

Mark D McBriar

Murali Rajagopalan

Jesse K Wong

Paul E McNamara

Xian Liang

Jean E Lachowicz

Thavalakulamgar Sasikumar

Mary Anne Caplen

Richard Spring

Yan Jin

David Cole

The present invention is directed to novel tricyclic heterocycles of structural formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved. 

Tricyclic heterocycles useful as dipeptidyl peptidase-IV inhibitors

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

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.

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 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

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

[object Object]

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

Growing community of inventors

Verona, NJ, United States of America

Martin Domalski