Semi-synthetic aristolactams--inhibitors of CDK2 enzyme.
Several analogs of aristolochic acids were isolated and derivatized into their lactam derivatives to study their inhibition in CDK2 assay. The study helped to derive some conclusions about the structure-activity relation around the phenanthrin moiety. Semi-synthetic aristolactam 21 showed good activity with inhibition IC50 of 35 nM in CDK2 assay. The activity of this compound was comparable to some of the most potent synthetic compounds reported in the literature.
Hegde
Vinod R
VR
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. vinod.hegde@spcorp.com
Borges
Scott
S
Pu
Haiyan
H
Patel
Mahesh
M
Gullo
Vincent P
VP
Wu
Bonnie
B
Kirschmeier
Paul
P
Williams
Michael J
MJ
Madison
Vincent
V
Fischmann
Thierry
T
Chan
Tze-Ming
TM
D034341:Aristolochic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D034341:Aristolochic Acids; D011720:Pyrazoles; D011804:Quinolines; D016203:CDC2 Protein Kinase