Aryl-substituted imidazoles

摘要

The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

主权项

1. A compound having the formula: wherein Ar1 and Ar2 are independently selected from: wherein each X is independently selected from N and CH; wherein each Y is independently selected from S and O; wherein each Q is independently selected from hydrogen, halogen, nitro, and C1-C4 alkyl; wherein Ar1 and Ar2 are different; wherein Ar1 and Ar2 have a cis relationship; wherein R1 is selected from hydrogen and C1-C4 alkyl and substituted with 0-2 groups selected from halogen, alkoxy, carboxymethyl, carboxyethyl, trifluoromethyl, trifluoromethoxy, and —SO2Me; wherein R2, R3, and R5 are independently selected from hydrogen, halogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, n-propoxyl, i-propoxyl, n-butoxyl, i-butoxyl, and t-butoxyl; wherein R4a-R4e are independently selected from hydrogen, halogen, alkyl, trifluoromethyl, trifluoromethoxy, alkoxy, and —SO2Me; wherein R6a and R6b are independently selected from hydrogen and C1-C4 alkyl, or wherein R6a and R6b together comprise ═O; wherein R7 and R8 are independently selected from hydrogen, methyl, and ethyl; wherein R9 is selected from hydrogen, halogen, methyl, ethyl, methoxy, ethoxy, carboxymethyl, and carboxyethyl; wherein R10 is selected from C1-C4 alkyl and Ar3; and wherein Ar3 is selected from: or a pharmaceutically acceptable salt thereof.