Literature DB >> 24900280

Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist.

Chu-Biao Xue1, Anlai Wang1, Qi Han1, Yingxin Zhang1, Ganfeng Cao1, Hao Feng1, Taisheng Huang1, Changsheng Zheng1, Michael Xia1, Ke Zhang1, Lingquan Kong1, Joseph Glenn1, Rajan Anand1, David Meloni1, D J Robinson1, Lixin Shao1, Lou Storace1, Mei Li1, Robert O Hughes2, Rajesh Devraj2, Philip A Morton2, D Joseph Rogier2, Maryanne Covington1, Peggy Scherle1, Sharon Diamond1, Tom Emm1, Swamy Yeleswaram1, Nancy Contel1, Kris Vaddi1, Robert Newton1, Greg Hollis1, Brian Metcalf1.   

Abstract

We report the discovery of a new (S)-3-aminopyrrolidine series of CCR2 antagonists. Structure-activity relationship studies on this new series led to the identification of 17 (INCB8761/PF-4136309) that exhibited potent CCR2 antagonistic activity, high selectivity, weak hERG activity, and an excellent in vitro and in vivo ADMET profile. INCB8761/PF-4136309 has entered human clinical trials.

Entities:  

Keywords:  CCR2; antagonist; chemokine; hERG

Year:  2011        PMID： 24900280      PMCID： PMC4018168          DOI： 10.1021/ml200199c

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  10 in total

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Authors:  Chu-Biao Xue; Anlai Wang; David Meloni; Ke Zhang; Ling Kong; Hao Feng; Joseph Glenn; Taisheng Huang; Yingxin Zhang; Ganfeng Cao; Rajan Anand; Changsheng Zheng; Michael Xia; Qi Han; D J Robinson; Lou Storace; Lixin Shao; Mei Li; Carrie M Brodmerkel; Maryanne Covington; Peggy Scherle; Sharon Diamond; Swamy Yeleswaram; Kris Vaddi; Robert Newton; Greg Hollis; Steven Friedman; Brian Metcalf
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4.  Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist.

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Journal:  Bioorg Med Chem Lett       Date:  2011-01-11       Impact factor: 2.823

5.  gamma-Lactams as glycinamide replacements in cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists.

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Journal:  Bioorg Med Chem Lett       Date:  2010-03-10       Impact factor: 2.823

6.  Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist.

Authors:  Chu-Biao Xue; Hao Feng; Ganfeng Cao; Taisheng Huang; Joseph Glenn; Rajan Anand; David Meloni; Ke Zhang; Lingquan Kong; Anlai Wang; Yingxin Zhang; Changsheng Zheng; Michael Xia; Lihua Chen; Hiroyuki Tanaka; Qi Han; D J Robinson; Dilip Modi; Lou Storace; Lixin Shao; Vaqar Sharief; Mei Li; Laurine G Galya; Maryanne Covington; Peggy Scherle; Sharon Diamond; Tom Emm; Swamy Yeleswaram; Nancy Contel; Kris Vaddi; Robert Newton; Greg Hollis; Steven Friedman; Brian Metcalf
Journal:  ACS Med Chem Lett       Date:  2011-03-31       Impact factor: 4.345

Review 7.  Recent developments in CCR2 antagonists.

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  10 in total
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5.  In-silico guided discovery of novel CCR9 antagonists.

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6.  Discovery of a 4-Azetidinyl-1-thiazoyl-cyclohexane CCR2 Antagonist as a Development Candidate.

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Review 9.  Small Molecules Drive Big Improvements in Immuno-Oncology Therapies.

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Review 10.  The Role of Stroma in Cholangiocarcinoma: The Intriguing Interplay between Fibroblastic Component, Immune Cell Subsets and Tumor Epithelium.

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