The United States of America, As Represented by the Secretary, Department of Health and Human Services

Zhen-Dan Shi

Terrence R Burke, Jr

Donald P Bottaro

Yang Gao

Gagani P Athauda

Marc Nicklaus

Chang-Qing Wei

Alessio Giubellino

Megan Peach

Nelly Tan

Sarah Choyke

Sang-Uk Kang

Derivatives and analogs of inhibitors of receptor tyrosine kinase c-Met, pharmaceutical compositions containing derivatives and analogs of c-Met inhibitors are provided. Methods of making derivatives and analogs of c-Met inhibitors and methods of use thereof are provided. 

Compositions and methods for inhibition of hepatocyte growth factor receptor c-Met signaling

Disclosed are compounds represented by the formula: or a pharmaceutically acceptable salt or isomer thereof, wherein R-Rare as defined in the specification. These compounds are targeted for use as inhibitors of SH2 domain binding with a phosphoprotein, and are contemplated for use in a number of diseases including cancer. Also disclosed are pharmaceutical compositions comprising a compound of the invention and a pharmaceutically acceptable carrier.

SH2 domain binding inhibitors

Disclosed are compounds for SH2 domain binding inhibition, for example, a compound of formula (I), wherein Ris a lipophile; R, in combination with the phenyl ring, is a phenylphosphate mimic group or a protected phenylphosphate mimic group; Ris hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of Rmay be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; Ris a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. The conformationally compounds provide enhanced binding affinity with SH2 domain protein. Also disclosed are a pharmaceutical compositions and a method for inhibiting an SH2 domain from binding with a phosphoprotein.

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Frederick, MD, United States of America

Zhen-Dan Shi