Potent heteroarylpiperidine and carboxyphenylpiperidine 1-alkyl-cyclopentane carboxamide CCR2 antagonists.
This report describes replacement of the 4-(4-fluorophenyl)piperidine moiety in our CCR2 antagonists with 4-heteroaryl piperidine and 4-(carboxyphenyl)-piperidine subunits. Some of the resulting analogs retained potency in our CCR2 binding assay and had improved selectivity versus the I(Kr) channel; poor selectivity against I(Kr) had been a liability of earlier analogs in this series.
Pasternak
Alexander
A
Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 126 East Lincoln Avenue, Rahway, NJ 07065, USA. alexander_pasternak@merck.com
Goble
Stephen D
SD
Vicario
Pasquale P
PP
Di Salvo
Jerry
J
Ayala
Julia M
JM
Struthers
Mary
M
DeMartino
Julie A
JA
Mills
Sander G
SG
Yang
Lihu
L
D000818:Animals; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D010880:Piperidines; D026902:Potassium Channel Blockers; D054390:Receptors, CCR2