Literature DB >> 25893046

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

Percy H Carter1, Gregory D Brown1, Robert J Cherney1, Douglas G Batt1, Jing Chen1, Cheryl M Clark1, Mary Ellen Cvijic1, John V Duncia1, Soo S Ko1, Sandhya Mandlekar1, Ruowei Mo1, David J Nelson1, Jian Pang1, Anne V Rose1, Joseph B Santella1, Andrew J Tebben1, Sarah C Traeger1, Songmei Xu1, Qihong Zhao1, Joel C Barrish1.   

Abstract

We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCR5. Installation of a γ-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.

Entities:  

Keywords:  Chemokine; GPCR; dual antagonist; inflammation

Year:  2015        PMID： 25893046      PMCID： PMC4394346          DOI： 10.1021/ml500505q

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


  19 in total

Review 1.  CCR2 antagonists.

Authors:  Mary Struthers; Alexander Pasternak
Journal:  Curr Top Med Chem       Date:  2010       Impact factor: 3.295

Review 2.  Monocyte and macrophage heterogeneity.

Authors:  Siamon Gordon; Philip R Taylor
Journal:  Nat Rev Immunol       Date:  2005-12       Impact factor: 53.106

Review 3.  The many roles of chemokines and chemokine receptors in inflammation.

Authors:  Israel F Charo; Richard M Ransohoff
Journal:  N Engl J Med       Date:  2006-02-09       Impact factor: 91.245

4.  Enantioselective synthesis of benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate using an iodolactamization as the key step.

Authors:  Carlton L Campbell; Carla Hassler; Soo S Ko; Matthew E Voss; Michael A Guaciaro; Percy H Carter; Robert J Cherney
Journal:  J Org Chem       Date:  2009-08-21       Impact factor: 4.354

5.  Discovery of an orally-bioavailable CC Chemokine Receptor 2 antagonist derived from an acyclic diaminoalcohol backbone.

Authors:  Percy H Carter; Gregory D Brown; Sarah R King; Matthew E Voss; Andrew J Tebben; Robert J Cherney; Sandhya Mandlekar; Yvonne C Lo; Gengjie Yang; Persymphonie B Miller; Peggy A Scherle; Qihong Zhao; Carl P Decicco
Journal:  Bioorg Med Chem Lett       Date:  2012-03-10       Impact factor: 2.823

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

Authors:  Robert J Cherney; Ruowei Mo; Michael G Yang; Zili Xiao; Qihong Zhao; Sandhya Mandlekar; Mary Ellen Cvijic; Israel F Charo; Joel C Barrish; Carl P Decicco; Percy H Carter
Journal:  Bioorg Med Chem Lett       Date:  2014-02-21       Impact factor: 2.823

7.  A novel series of N-(azetidin-3-yl)-2-(heteroarylamino)acetamide CCR2 antagonists.

Authors:  Nalin L Subasinghe; James Lanter; Thomas Markotan; Evan Opas; Sandra McKenney; Carl Crysler; Cuifen Hou; John O'Neill; Dana Johnson; Zhihua Sui
Journal:  Bioorg Med Chem Lett       Date:  2012-12-20       Impact factor: 2.823

Review 8.  Novel C-C chemokine receptor 2 antagonists in metabolic disease: a review of recent developments.

Authors:  Young Sun Kang; Jin Joo Cha; Young Youl Hyun; Dae Ryong Cha
Journal:  Expert Opin Investig Drugs       Date:  2011-04-06       Impact factor: 6.206

Review 9.  Progress in the discovery of CC chemokine receptor 2 antagonists, 2009 - 2012.

Authors:  Percy H Carter
Journal:  Expert Opin Ther Pat       Date:  2013-02-22       Impact factor: 6.674

Review 10.  Recent developments in CCR2 antagonists.

Authors:  Mingde Xia; Zhihua Sui
Journal:  Expert Opin Ther Pat       Date:  2009-03       Impact factor: 6.674
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  8 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

Review 2.  What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?

Authors:  Irina Kufareva; Martin Gustavsson; Yi Zheng; Bryan S Stephens; Tracy M Handel
Journal:  Annu Rev Biophys       Date:  2017-05-22       Impact factor: 12.981

Review 3.  Structural Analysis of Chemokine Receptor-Ligand Interactions.

Authors:  Marta Arimont; Shan-Liang Sun; Rob Leurs; Martine Smit; Iwan J P de Esch; Chris de Graaf
Journal:  J Med Chem       Date:  2017-03-10       Impact factor: 7.446

4.  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

5.  Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists.

Authors:  Yi Zheng; Ling Qin; Natalia V Ortiz Zacarías; Henk de Vries; Gye Won Han; Martin Gustavsson; Marta Dabros; Chunxia Zhao; Robert J Cherney; Percy Carter; Dean Stamos; Ruben Abagyan; Vadim Cherezov; Raymond C Stevens; Adriaan P IJzerman; Laura H Heitman; Andrew Tebben; Irina Kufareva; Tracy M Handel
Journal:  Nature       Date:  2016-12-07       Impact factor: 49.962

6.  A unique ligand-steered strategy for CC chemokine receptor 2 homology modeling to facilitate structure-based virtual screening.

Authors:  Hongwei Jin; Jie Xia; Zhenming Liu; Xiang Simon Wang; Liangren Zhang
Journal:  Chem Biol Drug Des       Date:  2021-01-16       Impact factor: 2.817

Review 7.  Pathogenesis and Therapeutic Strategies Related to Non-Alcoholic Fatty Liver Disease.

Authors:  Tieshan Teng; Shuai Qiu; Yiming Zhao; Siyuan Zhao; Dequan Sun; Lingzhu Hou; Yihang Li; Ke Zhou; Xixi Yu; Changyong Yang; Yanzhang Li
Journal:  Int J Mol Sci       Date:  2022-07-16       Impact factor: 6.208

8.  Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous Chemotactic Responses to Multiple Chemokines.

Authors:  Mohaned Ahmed; Haneen A Basheer; Jose M Ayuso; Djevdet Ahmet; Marco Mazzini; Roshan Patel; Steven D Shnyder; Victoria Vinader; Kamyar Afarinkia
Journal:  Sci Rep       Date:  2017-04-21       Impact factor: 4.379
  8 in total

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