Synthesis and biological evaluation of 3-ethylidene-1,3-dihydro-indol-2-ones as novel checkpoint 1 inhibitors.
Chk1 inhibitors have emerged as a novel class of neoplastic agents for abrogating the G2 DNA damage checkpoint arrest. Analogs of the Chk1 inhibitor, 3-ethylidene-1,3-dihydro-indol-2-one, were synthesized and tested in vitro for their inhibitory activities. The most promising compound identified from this series is analog 28, which possesses potent enzymatic and cellular activities.
Lin
Nan-Horng
NH
Cancer Research, R-47B, Global Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. nanhorng.lin@abbott.com
Xia
Ping
P
Kovar
Peter
P
Park
Chang
C
Chen
Zehan
Z
Zhang
Haiying
H
Rosenberg
Saul H
SH
Sham
Hing L
HL
D049109:Cell Proliferation / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011494:Protein Kinases / Q000187:drug effects*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1