Development of CXCR3 antagonists. Part 2: Identification of 2-amino(4-piperidinyl)azoles as potent CXCR3 antagonists.
Development of a lead series of piperidinylurea CXCR3 antagonists has led to the identification of molecules with alternative linkages which retain good potency. A novel 5-(piperidin-4-yl)amino-1,2,4-thiadiazole derivative was found to have satisfactory in vitro metabolic stability and to be orally bioavailable in mice, giving high plasma concentrations and a half life of 5.4h.
Watson
Robert J
RJ
UCB Inflammation Discovery, Granta Park, Great Abington, Cambridge CB21 6GS, United Kingdom.
Allen
Daniel R
DR
Birch
Helen L
HL
Chapman
Gayle A
GA
Hannah
Duncan R
DR
Knight
Roland L
RL
Meissner
Johannes W G
JW
Owen
David A
DA
Thomas
Elizabeth J
EJ
D000586:Amination; D000818:Animals; D001393:Azoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D001393:Azoles; D010880:Piperidines; D054367:Receptors, CXCR3; D014867:Water; C032727:piperidine