1028265-25-9Relevant academic research and scientific papers
Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. Part 4: Heterocycles at C3
Yue, Eddy W.,DiMeo, Susan V.,Higley, C. Anne,Markwalder, Jay A.,Burton, Catherine R.,Benfield, Pamela A.,Grafstrom, Robert H.,Cox, Sarah,Muckelbauer, Jodi K.,Smallwood, Angela M.,Chen, Haiying,Chang, Chong-Hwan,Trainor, George L.,Seitz, Steven P.
, p. 343 - 346 (2004)
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.
Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. 3. Structure activity relationships at C3
Yue, Eddy W.,Higley, C. Anne,DiMeo, Susan V.,Carini, David J.,Nugiel, David A.,Benware, Carrie,Benfield, Pamela A.,Burton, Catherine R.,Cox, Sarah,Grafstrom, Robert H.,Sharp, Diane M.,Sisk, Lisa M.,Boylan, John F.,Muckelbauer, Jodi K.,Smallwood, Angela M.,Chen, Haiying,Chang, Chong-Hwan,Seitz, Steven P.,Trainor, George L.
, p. 5233 - 5248 (2007/10/03)
The identification of indeno[1,2-c]pyrazol-4-ones as inhibitors of cyclin-dependent kinases (CDKs) has led to the discovery of a series of novel and potent compounds. Herein, we report the effects of substitutions at C3 of the indeno[1,2-c]pyrazol-4-one core with alkyls, heterocycles, and substituted phenyls. Substitutions at the para position of the phenyl ring at C3 were generally well-tolerated; however, larger groups were generally inactive. For alkyls directly attached to C3, longer chain substituents were not tolerated; however, shorter alkyl groups and cyclic alkyls were acceptable. In general, the heterocycles at C3 gave the most potent analogues. One such heterocycle, 24j, was examined in detail and was determined to have a biological profile consistent with CDK inhibition. An X-ray crystal structure of one of the alkyl compounds, 13q, complexed with CDK2 was determined and showed the inhibitor residing in the adenosine 5′-triphosphate pocket of the enzyme.
