Literature DB >> 28947948

Discovery of AZD-2098 and AZD-1678, Two Potent and Bioavailable CCR4 Receptor Antagonists.

Nicholas Kindon1, Glen Andrews1, Andrew Baxter1, David Cheshire1, Paul Hemsley1, Timothy Johnson1, Yu-Zhen Liu1, Dermot McGinnity1, Mark McHale1, Antonio Mete1, James Reuberson1, Bryan Roberts1, John Steele1,2, Barry Teobald1, John Unitt1, Deborah Vaughan1, Iain Walters1, Michael J Stocks1.   

Abstract

N-(5-Bromo-3-methoxypyrazin-2-yl)-5-chlorothiophene-2-sulfonamide 1 was identified as a hit in a CCR4 receptor antagonist high-throughput screen (HTS) of a subset of the AstraZeneca compound bank. As a hit with a lead-like profile, it was an excellent starting point for a CCR4 receptor antagonist program and enabled the rapid progression through the Lead Identification and Lead Optimization phases resulting in the discovery of two bioavailable CCR4 receptor antagonist candidate drugs.

Entities:  

Keywords:  CCR4; Chemokine receptor 4; MDC; TARC; antagonist

Year:  2017        PMID： 28947948      PMCID： PMC5601455          DOI： 10.1021/acsmedchemlett.7b00315

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


  21 in total

1.  An intracellular allosteric site for a specific class of antagonists of the CC chemokine G protein-coupled receptors CCR4 and CCR5.

Authors:  Glen Andrews; Carolyn Jones; Keith A Wreggett
Journal:  Mol Pharmacol       Date:  2007-11-27       Impact factor: 4.436

Review 2.  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

3.  Discovery of potent CCR4 antagonists: Synthesis and structure-activity relationship study of 2,4-diaminoquinazolines.

Authors:  Kazuhiro Yokoyama; Noriko Ishikawa; Susumu Igarashi; Noriyuki Kawano; Kazuyuki Hattori; Takahiro Miyazaki; Shin-ichi Ogino; Yuzo Matsumoto; Makoto Takeuchi; Mitsuaki Ohta
Journal:  Bioorg Med Chem       Date:  2008-05-20       Impact factor: 3.641

4.  Core exploration in optimization of chemokine receptor CCR4 antagonists.

Authors:  Ashok V Purandare; Honghe Wan; John E Somerville; Christine Burke; Wayne Vaccaro; XiaoXia Yang; Kim W McIntyre; Michael A Poss
Journal:  Bioorg Med Chem Lett       Date:  2006-11-02       Impact factor: 2.823

Review 5.  Chemokine receptor antagonists: Part 1.

Authors:  James E Pease; Richard Horuk
Journal:  Expert Opin Ther Pat       Date:  2009-01       Impact factor: 6.674

6.  Small molecule antagonists of the CC chemokine receptor 4 (CCR4).

Authors:  Douglas F Burdi; Shannon Chi; Karen Mattia; Celeste Harrington; Zhan Shi; Shaowu Chen; Swanee Jacutin-Porte; Robert Bennett; Kenneth Carson; Wei Yin; Vikram Kansra; Jose-Angel Gonzalo; Anthony Coyle; Bruce Jaffee; Timothy Ocain; Marty Hodge; Gregory LaRosa; Geraldine Harriman
Journal:  Bioorg Med Chem Lett       Date:  2007-03-15       Impact factor: 2.823

7.  Synthesis and structure-activity relationships of indazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists.

Authors:  Panayiotis A Procopiou; John W Barrett; Nicholas P Barton; Malcolm Begg; David Clapham; Royston C B Copley; Alison J Ford; Rebecca H Graves; David A Hall; Ashley P Hancock; Alan P Hill; Heather Hobbs; Simon T Hodgson; Coline Jumeaux; Yannick M L Lacroix; Afjal H Miah; Karen M L Morriss; Deborah Needham; Emma B Sheriff; Robert J Slack; Claire E Smith; Steven L Sollis; Hugo Staton
Journal:  J Med Chem       Date:  2013-02-27       Impact factor: 7.446

8.  CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge.

Authors:  C Pilette; J N Francis; S J Till; S R Durham
Journal:  Eur Respir J       Date:  2004-06       Impact factor: 16.671

9.  Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.

Authors:  R Bonecchi; G Bianchi; P P Bordignon; D D'Ambrosio; R Lang; A Borsatti; S Sozzani; P Allavena; P A Gray; A Mantovani; F Sinigaglia
Journal:  J Exp Med       Date:  1998-01-05       Impact factor: 14.307

10.  Antagonism of human CC-chemokine receptor 4 can be achieved through three distinct binding sites on the receptor.

Authors:  Robert J Slack; Linda J Russell; Nick P Barton; Cathryn Weston; Giovanna Nalesso; Sally-Anne Thompson; Morven Allen; Yu Hua Chen; Ashley Barnes; Simon T Hodgson; David A Hall
Journal:  Pharmacol Res Perspect       Date:  2013-12-30
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  6 in total

1.  CCR4 Antagonists Inhibit Treg Trafficking into the Tumor Microenvironment.

Authors:  John M Ketcham; Lisa A Marshall; Oezcan Talay
Journal:  ACS Med Chem Lett       Date:  2018-09-10       Impact factor: 4.345

Review 2.  Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review.

Authors:  Wan-Yin Fang; L Ravindar; K P Rakesh; H M Manukumar; C S Shantharam; Njud S Alharbi; Hua-Li Qin
Journal:  Eur J Med Chem       Date:  2019-04-10       Impact factor: 6.514

3.  CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes.

Authors:  Guomin Ren; Nedaa Al-Jezani; Pamela Railton; James N Powell; Roman J Krawetz
Journal:  iScience       Date:  2020-12-13

4.  Is CC Chemokine Ligand 17 (TARC) Driving Disease Progression in Chronic Obstructive Pulmonary Disease?

Authors:  Jason Girkin
Journal:  Am J Respir Cell Mol Biol       Date:  2022-04       Impact factor: 6.914

5.  Serum Analyte Profiles Associated With Crohn's Disease and Disease Location.

Authors:  Gabrielle Boucher; Alexandre Paradis; Geneviève Chabot-Roy; Lise Coderre; Erin E Hillhouse; Alain Bitton; Christine Des Rosiers; Megan K Levings; L Philip Schumm; Mark Lazarev; Steve R Brant; Richard Duerr; Dermot McGovern; Mark S Silverberg; Judy Cho; Sylvie Lesage; John D Rioux
Journal:  Inflamm Bowel Dis       Date:  2022-01-05       Impact factor: 7.290

Review 6.  Key chemokines direct migration of immune cells in solid tumors.

Authors:  Karan Kohli; Venu G Pillarisetty; Teresa S Kim
Journal:  Cancer Gene Ther       Date:  2021-02-18       Impact factor: 5.987
  6 in total

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