1.
Bioorg Med Chem Lett
; 19(20): 5887-92, 2009 Oct 15.
Article
in English
| MEDLINE
| ID: mdl-19762238
ABSTRACT
A series of phenylaminopyrimidines has been identified as inhibitors of Janus kinases (JAKs). Development of this initial series led to the potent JAK2/JAK1 inhibitor CYT387 (N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-benzamide). Details of synthesis and SAR studies of these compounds are reported.
Subject(s)
Benzamides/chemistry , Janus Kinase 2/antagonists & inhibitors , Protein Kinase Inhibitors/chemistry , Pyrimidines/chemistry , Animals , Benzamides/chemical synthesis , Benzamides/pharmacology , Binding Sites , Caco-2 Cells , Cell Line, Tumor , Computer Simulation , Humans , Janus Kinase 2/metabolism , Male , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/metabolism , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacokinetics , Pyrimidines/chemical synthesis , Pyrimidines/pharmacokinetics , Pyrimidines/pharmacology , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 19(16): 4639-42, 2009 Aug 15.
Article
in English
| MEDLINE
| ID: mdl-19616947
ABSTRACT
CYT997 was discovered as a potent tubulin polymerization inhibitor possessing potent cytotoxic activity against a range of cancer cells. Details of SAR studies, pharmacokinetic investigations and synthesis of compounds leading to the discovery of CYT997 are reported.