Synthesis and evaluation of cis-3,4-disubstituted piperidines as potent CC chemokine receptor 2 (CCR2) antagonists

Bioorganic & Medicinal Chemistry Letters
Robert J CherneyCarl P Decicco

Abstract

A series of cis-3,4-disubstituted piperidines was synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. Compound 24 emerged with an attractive profile, possessing excellent binding (CCR2 IC(50)=3.4 nM) and functional antagonism (calcium flux IC(50)=2.0 nM and chemotaxis IC(50)=5.4 nM). Studies to explore the binding of these piperidine analogs utilized a key CCR2 receptor mutant (E291A) with compound 14 and revealed a significant reliance on Glu291 for binding.

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Feb 1, 2008·Journal of Medicinal Chemistry·Robert J CherneyCarl P Decicco
Mar 4, 2008·Bioorganic & Medicinal Chemistry Letters·Wilna J MoreeChristine M Tarby

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Citations

Jun 1, 2010·Expert Opinion on Drug Discovery·Masilamani Elizabeth SobhiaSwapnil Chavan
Feb 8, 2011·Chemical Biology & Drug Design·Gugan KothandanSeung J Cho
Jun 28, 2011·British Journal of Pharmacology·D J ScholtenR Leurs
Jul 7, 2009·Biochemical and Biophysical Research Communications·Niu ShinPeggy A Scherle
Apr 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·Bryn C TaylorRommie E Amaro
May 16, 2009·Expert Opinion on Therapeutic Patents·James E Pease, Richard Horuk
May 3, 2020·Chemistry : a European Journal·Haibo MeiVadim A Soloshonok
Apr 22, 2015·ACS Medicinal Chemistry Letters·Percy H CarterJoel C Barrish
Mar 17, 2018·Journal of Medicinal Chemistry·Jared T HammillR Kiplin Guy

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