Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Tri-institutional Therapeutics Discovery Institute

Cornell University

Sloan-kettering Institute for Cancer Research

Evotec Oai

The Rockefeller University

Peter T Meinke

Michael H Fisher

Helmut H Mrozik

Harold B Wood

Kun Liu

John J Acton, Iii

Thomas L Shih

Regina M Black

Matthew J Wyvratt

William H Parsons

Prasun K Chakravarty

Steven L Colletti

Yong Zhang

Sheryl Davis Debenham

Sriram Tyagarajan

Michael Andrew Foley

Guo Q Shi

Howard C H Kuo

Stephen Colin Price

Soumya P Sahoo

Edward Andrew Boyd

James Francis Dropinski

Richard Berger

Dennis M Schmatz

Hiroo Koyama

Maria L Garcia

Gregory J Kaczorowski

Kevin D Dykstra

John David Ginn

Meng-Hsin Chen

Sandra J Rattray

Andrew Evan Denker

Kazuyoshi Aso

Timothy Hla

Maurizio Scaltriti

Ginger Xu-Qiang Yang

Yoshiyuki Fukase

Mayako Michino

Ayumu Sato

Irina Jilishitz

Carles Monterrubio Martinez

Yusuke Sasaki

Jose Manuel Baselga Torres

Hiroki Takahagi

Amaia Arruabarrena Aristorena

Naoto Uemura

Andrew Stamford

William J Polvino

Hideyuki Igawa

Asato Kina

Yasufimi Wada

Yasutomi Asano

Steven Charnick

Gary E Meininger

John A Wagner

Daniel Alan Heller

Stephen J O'Keefe

John Stibbard

Michelle B Ayer

Yosef Shamay

Makoto Fushimi

Nathaniel Kastan

A James Hudspeth

David John Huggins

Leigh Ashley Baxt

Rui Liang

John J Iii Acton

Stephen J O'KEEFE

Sheryl D Debenham

The development of a new, targeted drug delivery paradigm coupled to improved PI3K inhibitors (e.g., PI3Kα inhibitors) represents a significant advance in cancer therapy. Provided herein are compounds, such as compounds of Formula (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds provided herein are PI3K (e.g., PI3Kα) inhibitors and are therefore useful for the treatment and/or prevention of various diseases (e.g., proliferative diseases such as cancer). Also provided herein are nanoparticles and nanogels (e.g., P-selectin targeting nanoparticles) comprising PI3K inhibitors, such a compound described herein. In certain embodiments, a nanoparticle or nanogel described herein encapsulates a compound described herein for targeting delivery to cancer cells or tumors.

PI3K inhibitors and uses thereof

The various examples presented herein are directed to compounds of the formula A-L-Het-L-Cyor a pharmaceutical acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein: A is cycloalkyl, aryl, arylalkyl or heterocyclyl; Hetis heterocyclyl containing at least two heteroatoms; Cyis a heterocyclyl; Lis a bond, alkyl, alkenyl or alkynyl linker; Lis an acyl or alkyl linker; and A and Cyare different. The compounds are useful in the treatment of fibrotic diseases, abnormal vascular leak and pathological angiogenesis.

Pyridinone- and pyridazinone-based compounds and uses thereof

Fused aromatic compounds of Formula I are PPAR gamma agonists or partial agonists and are useful for weekly dosing in the treatment or control of type II diabetes, including hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity that are often associated with type 2 diabetes. 

Method of treatment using fused aromatic compounds having anti-diabetic activity

Compounds described by the chemical formula (I) or pharmaceutically acceptable salts thereof: are inhibitors of p38 and are useful in the treatment of inflammation such as in the treatment of asthma, COPD, ARDS, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions; inflamed joints, eczema, psoriasis or other inflammatory skin conditions such as sunburn; inflammatory eye conditions including conjunctivitis; pyresis, pain and other conditions associated with inflammation.

P38 kinase inhibiting agents

Fused aromatic compounds of Formula (I) are PPAR gamma agonists or partial agonists and are useful in the treatment or control of type II diabetes, including hyperglycemia, dyslipidermia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity that are often associated with type 2 diabetes. 

Fused-aromatic compounds having anti-diabetic activity

Phenoxyphenyl and phenoxybenzyl oxazolidine-2,4-diones and thiazolidine-2,4-diones are agonists or partial agonists of PPAR gamma and are useful in the treatment and control of hyperglycemia that is symptomatic of type II diabetes, as well as dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity that are often associated with type 2 diabetes.

Antidiabetic oxazolidinediones and thiazolidinediones

Indoles of Formula I having &#x2014;X-aryl-(CH)-oxazolidinedione and &#x2014;X-heteroaryl-(CH)x-oxazolidinedione substituents on the N atom of the indole ring, where x is 0 or 1, and &#x2014;X&#x2014; is a bond or &#x2014;CH&#x2014;, and their thiazolidinedione analogs, are PPAR gamma agonists or partial agonists and are useful in the treatment and control of type II diabetes, including hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity that are often associated with type 2 diabetes. 

Indoles having anti-diabetic activity

This invention relates to the use of potent potassium channel blockers or a formulation thereof in the treatment of glaucoma and other conditions which leads to elevated intraoccular pressure in the eye of a patient. This invention also relates to the use of such compounds to provide a neuroprotective effect to the eye of mammalian species, particularly humans.

Ophthalmic compositions for treating ocular hypertension

Indoles having aryloxyalkanoic acid substituents or arylalkanoic acid substituents are agonists or partial agonists of PPAR gamma and are useful in the treatment and control of hyperglycemia that is symptomatic of type II diabetes, as well as dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity that are often associated with type 2 diabetes.

Aryl-link-aryl thiazolidine-dione and aryl-link-aryl oxazolidine-dione compounds are sodium channel blockers; pharmaceutical compositions that include an effective amount of the aryl-link-aryl thiazolidine-dione and aryl-link-aryl oxazolidine-dione compounds and a pharmaceutically acceptable carrier, and a method of treatment of acute pain, chronic pain, visceral pain, inflammatory pain, or neuropathic pain, as well as initable bowel syndrome, Cnohns disease, epilepsy, partial and generalized tonic seizures, multiple sclerosis, bipolar depression, and tachy-arrhythmias by the administration of an effective amount of aryl-link-aryl thiazolidine-dione and aryl-link-aryl oxazolidine-dione compounds are described.

Aryl-link-aryl substituted thiazolidine-dione and oxazolidine-dione as sodium channel blockers

The present invention relates to novel nodulosporic acid derivatives, which are acaricidal, antiparasitic, insecticidal and anthelmintic agents.

C1 to C4 side chain modified nodulisporic acid analogs

Nonacyclic nodulisporic acid derivatives

Nodulisporic acid derivatives

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Scotch Plains, NJ, United States of America

Peter T Meinke