943747-42-0Relevant articles and documents
4-(Phenylaminomethylene)isoquinoline-1,3(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4 (CDK4)
Tsou, Hwei-Ru,Otteng, Mercy,Tran, Tritin,Floyd Jr., M. Brawner,Reich, Marvin,Birnberg, Gary,Kutterer, Kristina,Ayral-Kaloustian, Semiramis,Ravi, Malini,Nilakantan, Ramaswamy,Grillo, Mary,McGinnis, John P.,Rabindran, Sridhar K.
experimental part, p. 3507 - 3525 (2009/04/07)
The cyclin-dependent kinases (CDKs), as complexes with their respective partners, the cyclins, are critical regulators of cell cycle progression. Because aberrant regulations of CDK4/cyclin D1 lead to uncontrolled cell proliferation, a hallmark of cancer, small-molecule inhibitors of CDK4/cyclin D1 are attractive as prospective antitumor agents. The series of 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)-dione derivatives reported here represents a novel class of potent inhibitors that selectively inhibit CDK4 over CDK2 and CDK1 activities. In the headpiece of the 4-(phenylaminomethylene) isoquinoline-1,3(2H,4H)-dione, a basic amine substitutent is required on the aniline ring for the CDK4 inhibitory activity. The inhibitory activity is further enhanced when an aryl or heteroaryl substituent is introduced at the C-6 position of the isoquinoline-1,3(2H,4H)-dione core. We present here SAR data and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors.
