Sugen Incorporated

The Scripps Research Institute

Other

Agouron Pharmaceuticals, Inc.

Marcel Koenig

Peng Cho Tang

Chung Chen Wei

Yuanjun He

Jingrong Jean Cui

Tomas Vojkovsky

Fang-Jie Zhang

Walter Morozowich

Congxin Liang

Steven Huy Do

Malcolm Wilson Moon

Theodore M Kamenecka

Ping Gao

Patrick Griffin

Anne-Laure Blayo

Youseung Shin

Ping Huang

Asaad S Nematalla

Xiaoyuan Li

Hong Shen

Connie Li Sun

Ji Yu Chu

Yong Zhou

Ruofei Zhang

Par Holmberg

Alice Asteian

Gerald McMahon

John Yudhistir Ramphal

Bahija Jallal

Pär Holmberg

Thomas Burris

Sharon Li

Chris Liang

John Biltz

Matt Mattson

Naresh Kumar

Brent R Lyda

The invention provides small molecule modulators of retinoic acid receptor-related orphan receptors such as ROR&#x3b1;, ROR&#x3b2;, or ROR&#x3b3;, of formula with the variable atoms as defined herein and Rcomprising a hydroxyl- or alkoxyl-substituted fluoroalkyl group. Compounds of the invention can be effective modulators at concentrations ineffective to act on LXR receptors, or on other nuclear receptors, or other biological targets. Methods of modulation the RORs and methods of treating metabolic disorders, immune disorders, cancer, and CNS disorders wherein modulation of an ROR is medically indicated are also provided.

Modulators of the nuclear hormone receptor ROR

The invention provides inhibitors of focal adhesion kinase, an enzyme involved in the attachment of the cytoskeleton of a cell to an extracellular matrix, which has been implicated in processes such as cell migration, cell proliferation, and cell survival. The inhibitors are derivatives of a 5-substituted 2,4-diaminopyridine wherein the substituents are as defined herein. The invention also provides a method of using the inhibitors in treatment of cancer, and methods of preparation of the inhibitors by use of coupling reactions.

Inhibitors of focal adhesion kinase

The invention provides molecular entities that bind with high affinity to PPARG (PPAR&#x3b3;), and inhibit kinase-mediated (e.g., cdk5-mediated) phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes, insulin resistance, impaired glucose tolerance, pre-diabetes, hyperglycemia, hyperinsulinemia, obesity, or inflammation. Side effects such as significant weight gain, edema, impairment of bone growth or formation, or cardiac hypertrophy, or any combination thereof, can be avoided in the mammal receiving the compound. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.

N-benzylindole modulators of PPARG

The invention provides molecular entities that bind with high affinity to PPARG (PPAR&#x3b3;), inhibit kinase-mediated, e.g., cdk5-mediated, phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes, insulin resistance, impaired glucose tolerance, pre-diabetes, hyperglycemia, hyperinsulinemia, obesity, or inflammation. In methods of treatment of these conditions using a compound of the invention, the compound can avoid producing side effects of significant weight gain, edema, impairment of bone growth or formation, or cardiac hypertrophy, or any combination thereof, in the patient receiving the compound. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.

N-biphenylmethylindole modulators of PPARG

The present invention relates to compounds of the Formula (I), and their pharmaceutically acceptable salts. These compounds modulate the activity of c-Met and are therefore expected to be useful in the prevention and treatment of c-Met related disorders such as cancer

Triazolotriazine compounds and uses thereof

The present invention is directed to prodrugs of certain 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that modulate the activity of protein kinases ('PKs'). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.

Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives

The present invention relates to pyrrole substituted 2-indolinone compounds and their pharmaceutically acceptable salts which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.

Prodrugs of a 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives

The present invention relates to compounds of the Formulae (I) and (II), wherein R-Rand G are defined herein, and their pharmaceutically acceptable salts. These compounds modulate the activity of c-Met and are therefore expected to be useful in the prevention and treatment of c-Met related disorders such as cancer.

Tetracyclic compounds as c-Met inhibitors

The present invention relates to 4-arylindolinones, as well as pharmaceutical compositions thereof, capable of modulating protein kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation. The present invention also relates to methods for treating protein kinase related disorders.

4-aryl substituted indolinones

The present invention is directed to prodrugs of certain 3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that modulate the activity of protein kinases (&ldquo;PKs&rdquo;). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.

The invention relates to trifluoromethyl sulfonyl and trifluoromethyl sulfonamido compounds and the physiologically acceptable salts and the prodrugs thereof. These compounds are expected to modulate the activity of protein tyrosine enzymes which are related to cellular signal transduction, in particular, protein tyrosine phosphatase, and therefore are expected to be useful in the prevention and treatment of disorders associated with abnormal protein tyrosine enzyme related cellular signal transduction such as cancer, diabetes, immuno-modulation, neurologic degenerative diseases, osteoporosis and infectious diseases. The invention also relates to the use of compounds containing fluoromethyl sulfonyl groups as phosphate mimics. These mimics may be used to inhibit, regulate or modulate the activity of a phosphate binding protein in a cell.

Phosphate mimics and methods of treatment using phosphatase inhibitors

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Burlingame, CA, United States of America

Marcel Koenig