Eolas Therapeutics, Inc.

The Scripps Research Institute

Astrazeneca Ab

Yuanjun He

Theodore M Kamenecka

Marcel Koenig

Robert Jason Herr

Qin Jiang

Patrick Griffin

Steven Sigmund Wesolowski

Rong Jiang

Xinyi Song

Youseung Shin

Anne-Laure Blayo

William Nguyen

Congxin Liang

Roland W Bürli

Jörg Holenz

Pär Holmberg

Alice Asteian

Par Holmberg

Roland Burli

Brent R Lyda

Roland Bürli

Naresh Kumar

Thomas Burris

Jorg Holenz

Steven Wesolowski

Roland BÜRLI

The present application relates to certain halo-substituted piperidine compounds, pharmaceutical compositions containing them, and methods of using them, including methods for treating substance addiction, panic disorder, anxiety, post-traumatic stress disorder, pain, depression, seasonal affective disorder, an eating disorder, or hypertension.

Halo-substituted piperidines as orexin receptor modulators

The present application relates to certain difluoropyrrolidine compounds, pharmaceutical compositions containing them, and methods of using them, including methods for treating substance addiction, panic disorder, anxiety, post-traumatic stress disorder, pain, depression, seasonal affective disorder, an eating disorder, or hypertension.

Difluoropyrrolidines as orexin receptor modulators

The present invention is directed to compounds that modulate the bioactivity of an orexin receptor such as OXor OX, or both; to pharmaceutical compositions and combinations comprising a compound of the invention; to methods of treatment of malconditions in patients wherein modulation of an orexin receptor is medically indicated; and to methods of preparation of compounds of the invention. For example, orexin receptor-modulatory compounds of the present invention can be used in treatment of an eating disorder, obesity, alcoholism or an alcohol-related disorder, drug abuse or addiction including addiction to cocaine, opiates, amphetamines, or nicotine, a sleep disorder, a cognitive dysfunction in a psychiatric or neurologic disorder, depression, anxiety, panic disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, headache, migraine, pain, gastrointestinal diseases, epilepsy, inflammations, immune-related diseases, endocrine-related diseases, cancer, hypertension, behavior disorder, mood disorder, manic depression, dementia, sex disorder, psychosexual disorder, or renal disease.

Substituted prolines/piperidines as orexin receptor antagonists

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

Substituted prolines / piperidines as orexin receptor antagonists

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

Growing community of inventors

Palm Beach Gardens, FL, United States of America

Yuanjun He