1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.
A series of 1-acyl-1H-[1,2,4]triazole-3,5-diamine analogues were synthesized as cyclin-dependent kinase (CDK) inhibitors. These compounds showed potent and selective CDK1 and CDK2 inhibitory activities and inhibited in vitro cellular proliferation in various human tumor cells. Representative compound 3b demonstrated in vivo efficacy in a human melanoma A375 xenograft model in nude mice.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Drug Discovery, 1000 Route 202, Raritan, New Jersey 08869, USA. rlin@prdus.jnj.com
Ronghui
R
Lin
Peter J
PJ
Connolly
Shenlin
S
Huang
Steven K
SK
Wetter
Yanhua
Y
Lu
William V
WV
Murray
Stuart L
SL
Emanuel
Robert H
RH
Gruninger
Angel R
AR
Fuentes-Pesquera
Catherine A
CA
Rugg
Steven A
SA
Middleton
Linda K
LK
Jolliffe
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D003959:Diamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
D000970:Antineoplastic Agents; D003959:Diamines; D004791:Enzyme Inhibitors; D014230:Triazoles; D018844:Cyclin-Dependent Kinases