Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series

  • Bioorg Med Chem Lett. 2008 Mar 15;18(6):1869-73. doi: 10.1016/j.bmcl.2008.02.015.
Wilna J Moree  1 ,  Ken-ichiro Kataoka ,  Michele M Ramirez-Weinhouse ,  Tatsuki Shiota ,  Minoru Imai ,  Takaharu Tsutsumi ,  Masaki Sudo ,  Noriaki Endo ,  Yumiko Muroga ,  Takahiko Hada ,  Dewey Fanning ,  John Saunders ,  Yoshinori Kato ,  Peter L Myers ,  Christine M Tarby
Affiliations
  • 1. Deltagen Research Laboratories (Former CombiChem, Inc.), 4570 Executive Drive, San Diego, CA 92121, USA. [email protected]
PMID: 18313297 DOI: 10.1016/j.bmcl.2008.02.015
Abstract

SAR studies were conducted around lead compound 1 using high-throughput parallel solution and solid phase synthesis. Our lead optimization efforts led to the identification of several CCR2b antagonists with potent activity in both binding and functional assays [Compound 71 CCR2b Binding IC(50) 3.2 nM; MCP-1-Induced Chemotaxis IC(50) 0.83 nM; CA(2+) Flux IC(50) 7.5 nM].

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