Design, synthesis, and structure–activity relationship of novel CCR2 antagonists

Discovery of a novel series of 3-aminocyclopentanecarboxamide CCR2 receptor antagonists are presented herein. These compounds demonstrate high affinity and functional inhibition of hCCR2 receptors. A discussion on SAR along with the cross species PK profile for the best analog ( 59) is also included. A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog 59 was found to posses potent antagonistic activity.