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.
Lin
Ronghui
R
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Drug Discovery, 1000 Route 202, Raritan, New Jersey 08869, USA. rlin@prdus.jnj.com
Connolly
Peter J
PJ
Huang
Shenlin
S
Wetter
Steven K
SK
Lu
Yanhua
Y
Murray
William V
WV
Emanuel
Stuart L
SL
Gruninger
Robert H
RH
Fuentes-Pesquera
Angel R
AR
Rugg
Catherine A
CA
Middleton
Steven A
SA
Jolliffe
Linda K
LK
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