Semi-synthetic aristolactams--inhibitors of CDK2 enzyme

Vinod R Hegde; Scott Borges; Haiyan Pu; Mahesh Patel; Vincent P Gullo; Bonnie Wu; Paul Kirschmeier; Michael J Williams; Vincent Madison; Thierry Fischmann; Tze-Ming Chan

doi:10.1016/j.bmcl.2010.01.007

Semi-synthetic aristolactams--inhibitors of CDK2 enzyme

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1384-7. doi: 10.1016/j.bmcl.2010.01.007. Epub 2010 Jan 7.

Authors

Vinod R Hegde¹, Scott Borges, Haiyan Pu, Mahesh Patel, Vincent P Gullo, Bonnie Wu, Paul Kirschmeier, Michael J Williams, Vincent Madison, Thierry Fischmann, Tze-Ming Chan

Affiliation

¹ Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. vinod.hegde@spcorp.com

PMID: 20097066
DOI: 10.1016/j.bmcl.2010.01.007

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.

MeSH terms

Aristolochic Acids / chemical synthesis*
Aristolochic Acids / chemistry
Aristolochic Acids / pharmacology
CDC2 Protein Kinase / antagonists & inhibitors*
Cell Line, Tumor
Computer Simulation
Crystallography, X-Ray
Humans
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology
Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology
Structure-Activity Relationship

Substances

Aristolochic Acids
Pyrazoles
Quinolines
CDC2 Protein Kinase