Literature DB >> 24613378

Alkylsulfone-containing trisubstituted cyclohexanes as potent and bioavailable chemokine receptor 2 (CCR2) antagonists.

Robert J Cherney1, Ruowei Mo2, Michael G Yang2, Zili Xiao2, Qihong Zhao2, Sandhya Mandlekar2, Mary Ellen Cvijic2, Israel F Charo3, Joel C Barrish2, Carl P Decicco2, Percy H Carter2.   

Abstract

We describe novel alkylsulfones as potent CCR2 antagonists with reduced hERG channel activity and improved pharmacokinetics over our previously described antagonists. Several of these new alkylsulfones have a profile that includes functional antagonism of CCR2, in vitro microsomal stability, and oral bioavailability. With this improved profile, we demonstrate that two of these antagonists, 2 and 12, are orally efficacious in an animal model of inflammatory recruitment.
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  CCR2; CCR2 antagonist; Chemokine antagonist; GPCR

Mesh：

Substances：

Year:  2014        PMID： 24613378      PMCID： PMC4539253          DOI： 10.1016/j.bmcl.2014.02.013

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  19 in total

1.  Properties of HERG channels stably expressed in HEK 293 cells studied at physiological temperature.

Authors:  Z Zhou; Q Gong; B Ye; Z Fan; J C Makielski; G A Robertson; C T January
Journal:  Biophys J       Date:  1998-01       Impact factor: 4.033

2.  Kinetics of changes in peritoneal cell populations following acute inflammation.

Authors:  M J Melnicoff; P K Horan; P S Morahan
Journal:  Cell Immunol       Date:  1989-01       Impact factor: 4.868

3.  Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance.

Authors:  Nozomu Kamei; Kazuyuki Tobe; Ryo Suzuki; Mitsuru Ohsugi; Taku Watanabe; Naoto Kubota; Norie Ohtsuka-Kowatari; Katsuyoshi Kumagai; Kentaro Sakamoto; Masatoshi Kobayashi; Toshimasa Yamauchi; Kohjiro Ueki; Yumiko Oishi; Satoshi Nishimura; Ichiro Manabe; Haruo Hashimoto; Yasuyuki Ohnishi; Hitomi Ogata; Kumpei Tokuyama; Masaki Tsunoda; Tomohiro Ide; Koji Murakami; Ryozo Nagai; Takashi Kadowaki
Journal:  J Biol Chem       Date:  2006-06-29       Impact factor: 5.157

Review 4.  Involvement of chemokine receptor 2 and its ligand, monocyte chemoattractant protein-1, in the development of atherosclerosis: lessons from knockout mice.

Authors:  W Peters; I F Charo
Journal:  Curr Opin Lipidol       Date:  2001-04       Impact factor: 4.776

Review 5.  Chemokine inhibition in inflammatory arthritis.

Authors:  Paul P Tak
Journal:  Best Pract Res Clin Rheumatol       Date:  2006-10       Impact factor: 4.098

Review 6.  Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: therapeutic opportunities and controversies.

Authors:  Christine Daly; Barrett J Rollins
Journal:  Microcirculation       Date:  2003-06       Impact factor: 2.628

Review 7.  The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE).

Authors:  Don J Mahad; Richard M Ransohoff
Journal:  Semin Immunol       Date:  2003-02       Impact factor: 11.130

8.  Bioactive conformation of luteinizing hormone-releasing hormone: evidence from a conformationally constrained analog.

Authors:  R M Freidinger; D F Veber; D S Perlow; J R Brooks; R Saperstein
Journal:  Science       Date:  1980-11-07       Impact factor: 47.728

9.  Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2.

Authors:  Natalya V Serbina; Eric G Pamer
Journal:  Nat Immunol       Date:  2006-02-05       Impact factor: 25.606

Review 10.  Monocyte chemoattractant protein-1 and atherosclerosis: is there room for an additional biomarker?

Authors:  Blai Coll; Carlos Alonso-Villaverde; Jorge Joven
Journal:  Clin Chim Acta       Date:  2007-05-03       Impact factor: 3.786
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  3 in total

1.  Use of a Conformational-Switching Mechanism to Modulate Exposed Polarity: Discovery of CCR2 Antagonist BMS-741672.

Authors:  Michael G Yang; Zili Xiao; Robert J Cherney; Andrew J Tebben; Douglas G Batt; Gregory D Brown; Jing Chen; Mary Ellen Cvijic; Marta Dabros; John V Duncia; Michael Galella; Daniel S Gardner; Purnima Khandelwal; Soo S Ko; Mary F Malley; Ruowei Mo; Jian Pang; Anne V Rose; Joseph B Santella; Hong Shi; Anurag Srivastava; Sarah C Traeger; Bei Wang; Songmei Xu; Rulin Zhao; Joel C Barrish; Sandhya Mandlekar; Qihong Zhao; Percy H Carter
Journal:  ACS Med Chem Lett       Date:  2019-01-16       Impact factor: 4.345

2.  Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5.

Authors:  Percy H Carter; Gregory D Brown; Robert J Cherney; Douglas G Batt; Jing Chen; Cheryl M Clark; Mary Ellen Cvijic; John V Duncia; Soo S Ko; Sandhya Mandlekar; Ruowei Mo; David J Nelson; Jian Pang; Anne V Rose; Joseph B Santella; Andrew J Tebben; Sarah C Traeger; Songmei Xu; Qihong Zhao; Joel C Barrish
Journal:  ACS Med Chem Lett       Date:  2015-03-04       Impact factor: 4.345

3.  Discovery of BMS-753426: A Potent Orally Bioavailable Antagonist of CC Chemokine Receptor 2.

Authors:  Michael G Yang; Zili Xiao; Rulin Zhao; Andrew J Tebben; Bei Wang; Robert J Cherney; Douglas G Batt; Gregory D Brown; Mary Ellen Cvijic; John V Duncia; Michael A Gallela; Daniel S Gardner; Purnima Khandelwal; Mary F Malley; Jian Pang; Anne V Rose; Joseph B Santella; Amy A Sarjeant; Songmei Xu; Arvind Mathur; Sandhya Mandlekar; Ragini Vuppugalla; Qihong Zhao; Percy H Carter
Journal:  ACS Med Chem Lett       Date:  2021-05-25       Impact factor: 4.632
  3 in total

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