Protein kinase C inhibitors and uses thereof

摘要

This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

主权项

1. A method of inhibiting a protein kinase C (PKC) activity in a biological sample or a patient, which method comprises contacting the biological sample or administering to the patient a compound of formula (I): wherein R5 is selected from alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halogen, acyl, aminoacyl, nitro, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl; Y is selected from hydrogen and alkyl; R1 is selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, acyl, and oxy radical; Ra and Rb are independently selected from hydrogen and alkyl; Rc and Rd are independently selected from hydrogen and alkyl; Q is CR7b; R7a is tetrazolyl or substituted tetrazolyl; R7b and R8 are independently selected from hydrogen, alkyl, substituted alkyl, halogen, cyano, hydroxyl, alkoxy, substituted alkoxy, amino, substituted amino, acylamino, aminocarbonyloxy, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxycarbonylamino, aminocarbonylamino, acyl, carboxyl, carboxyl ester, aminoacyl, sulfonyl, sulfonylamino, aminosulfonyl, and —O-alk-A; alk, if present, is alkyl or substituted alkyl; A is selected from aryl, cycloalkyl, heteroaryl, and heterocyclyl; wherein the A ring can be substituted or unsubstituted; or a salt or stereoisomer thereof.