National Institutes of Health, a Component of the US Dept. of Health & Human Services

Chang-Qing Wei

Terrence R Burke, Jr

Yang Gao

Johannes H Voigt

Zhen-Dan Shi

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.

SH2 domain binding inhibitors

Disclosed are compounds for SH2 domain binding inhibition. For example, disclosed is a compound of formula (I)wherein Ris a lipophile; R, in combination with the phenyl ring, forms 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. Also disclosed are a pharmaceutical composition, a method for inhibiting an SH2 domain from binding with a phosphoprotein and a method of treating breast cancer.

Growing community of inventors

Ottawa, Canada

Chang-Qing Wei