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

  • ACS Med Chem Lett. 2017 Sep 1;8(9):981-986. doi: 10.1021/acsmedchemlett.7b00315.
Nicholas Kindon  1 ,  Glen Andrews  1 ,  Andrew Baxter  1 ,  David Cheshire  1 ,  Paul Hemsley  1 ,  Timothy Johnson  1 ,  Yu-Zhen Liu  1 ,  Dermot McGinnity  1 ,  Mark McHale  1 ,  Antonio Mete  1 ,  James Reuberson  1 ,  Bryan Roberts  1 ,  John Steele  1  2 ,  Barry Teobald  1 ,  John Unitt  1 ,  Deborah Vaughan  1 ,  Iain Walters  1 ,  Michael J Stocks  1
Affiliations
  • 1. AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, LE11 5RH, U.K.
  • 2. Respiratory, Inflammation and Autoimmunity, Innovative Medicines and Early Development, AstraZeneca Gothenburg, Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
PMID: 28947948 DOI: 10.1021/acsmedchemlett.7b00315
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.

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