The discovery of tetrahydro-beta-carbolines as inhibitors of the kinesin Eg5.
A series of tetrahydro-beta-carbolines were identified by HTS as inhibitors of the kinesin Eg5. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of removing potential metabolic liabilities and improving cellular potency.
Barsanti
Paul A
PA
Global Discovery Chemistry/Oncology and Exploratory Chemistry, Novartis Institutes for Biomedical Research, 5400 Hollis Street, Emeryville, CA 94608, USA. paul.barsanti@novartis.com
Wang
Weibo
W
Ni
Zhi-Jie
ZJ
Duhl
David
D
Brammeier
Nathan
N
Martin
Eric
E
Bussiere
Dirksen
D
Walter
Annette O
AO
D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D057166:High-Throughput Screening Assays; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D051381:Rats; D013329:Structure-Activity Relationship
D002243:Carbolines; D004791:Enzyme Inhibitors; D016547:Kinesins