| abstract |
Disclosed are 2-arylamino-quinazoline derivatives as represented by the general formula (I) which modulate the Hedgehog pathway, wherein: R2 and R3 together with the pyrimidinyl to which they are attached form a quinazoline ring which is optionally substituted at the 5-, 6-, 7-, and 8-positions; R1 is alkyl, cycloalkyl, phenyl, or heteroaryl where the cycloalkyl, phenyl, and heteroaryl are optionally substituted; R40 is hydrogen or alkyl; R50 is a benzamide derivative as defined; and wherein the remaining substituents are as defined herein. Of particular importance are the compounds 4-[(4-phenylquinazolin-2-yl)amino]-N-(1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide; and N-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-morpholin-4-ylquinazolin-2-yl)amino]benzamide. Further disclosed is a pharmaceutical composition which comprises a compound as defined above, or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, and a pharmaceutically acceptable carrier, excipient, or diluent; for the treatment of diseases such as cancer, and particularly for the treatment of basal cell carcinoma, medulloblastoma, rhabdomyosaracoma, pancreatic cancer, breast carcinoma, meningioma, glioblastoma, melanoma, stomach cancer, esophageal cancer, biliary tract cancer, prostate cancer, small cell lung cancer, non-small cell lung cancer, glial cell cancer, multiple myeloma, chronic myeloid leukemia, testicular cancer, ovarian cancer, and colon cancer. |