Sh2 domain binding inhibitors

摘要

Disclosed are compounds for SH2 domain binding inhibition, for example, a compound of formula (I), wherein R₁ is a lipophile; R₂, in combination with the phenyl ring, is a phenylphosphate mimic group or a protected phenylphosphate mimic group; R₃ is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R₃ may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R₆ is 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.