Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. Part 4: Heterocycles at C3.
New indeno[1,2-c]pyrazol-4-one cyclin dependent kinase inhibitors have been disclosed. The most promising compounds are nanomolar enzyme inhibitors with excellent activity against tumor cells. The most advanced compound retains cell culture activity even in the presence of human serum proteins. The most advanced compound did not kill the normal fibroblast line AG1523.
Yue
Eddy W
EW
Bristol-Myers Squibb Company, Experimental Station, PO Box 80500, Wilmington, DE 19880-0500, USA. eddyyue@incyte.com
DiMeo
Susan V
SV
Higley
C Anne
CA
Markwalder
Jay A
JA
Burton
Catherine R
CR
Benfield
Pamela A
PA
Grafstrom
Robert H
RH
Cox
Sarah
S
Muckelbauer
Jodi K
JK
Smallwood
Angela M
AM
Chen
Haiying
H
Chang
Chong Hwan
CH
Trainor
George L
GL
Seitz
Steven P
SP
D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D011720:Pyrazoles; D018844:Cyclin-Dependent Kinases