1352934-53-2Relevant academic research and scientific papers
A novel series of N-(azetidin-3-yl)-2-(heteroarylamino)acetamide CCR2 antagonists
Subasinghe, Nalin L.,Lanter, James,Markotan, Thomas,Opas, Evan,McKenney, Sandra,Crysler, Carl,Hou, Cuifen,O'Neill, John,Johnson, Dana,Sui, Zhihua
, p. 1063 - 1069 (2013/03/13)
The inflammatory response associated with the activation of C-C chemokine receptor CCR2 via it's interaction with the monocyte chemoattractant protein-1 (MCP-1, CCL2) has been implicated in many disease states, including rheumatoid arthritis, multiple sclerosis, atherosclerosis, asthma and neuropathic pain. Small molecule antagonists of CCR2 have been efficacious in animal models of inflammatory disease, and have been advanced into clinical development. The necessity to attenuate hERG binding appears to be a common theme for many of the CCR2 antagonist scaffolds appearing in the literature, presumably due the basic hydrophobic motif present in all of these molecules. Following the discovery of a novel cyclohexyl azetidinylamide CCR2 antagonist scaffold, replacement of the amide bond with heterocyclic rings was explored as a strategy for reducing hERG binding and improving pharmacokinetic properties.
CYCLOHEXYL-AZETIDINYL ANTAGONISTS OF CCR2
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Page/Page column 127, (2012/01/06)
The present invention comprises compounds of Formula (I). Wherein: R1, R2, R4, J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).
