title: Semi-synthetic aristolactams--inhibitors of CDK2 enzyme.
abstract: 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.
authors.affiliation: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. vinod.hegde@spcorp.com
authors.forename: Vinod R
authors.initials: VR
authors.lastname: Hegde
authors.forename: Scott
authors.initials: S
authors.lastname: Borges
authors.forename: Haiyan
authors.initials: H
authors.lastname: Pu
authors.forename: Mahesh
authors.initials: M
authors.lastname: Patel
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Gullo
authors.forename: Bonnie
authors.initials: B
authors.lastname: Wu
authors.forename: Paul
authors.initials: P
authors.lastname: Kirschmeier
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Williams
authors.forename: Vincent
authors.initials: V
authors.lastname: Madison
authors.forename: Thierry
authors.initials: T
authors.lastname: Fischmann
authors.forename: Tze-Ming
authors.initials: TM
authors.lastname: Chan
mesh_terms: 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
chemical_list: D034341:Aristolochic Acids; D011720:Pyrazoles; D011804:Quinolines; D016203:CDC2 Protein Kinase