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Bioorg Med Chem Lett. 2015 Apr 1;25(7):1616-20. doi: 10.1016/j.bmcl.2015.01.067. Epub 2015 Feb 3.

Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists.

Author information

1
AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK.
2
AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK; Respiratory, Inflammation & Autoimmunity iMed, AstraZeneca R&D Mölndal, Pepparedsleden, 431 83 Mölndal, Sweden. Electronic address: rhona.cox@astrazeneca.com.
3
AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK; Respiratory, Inflammation & Autoimmunity iMed, AstraZeneca R&D Mölndal, Pepparedsleden, 431 83 Mölndal, Sweden.
4
AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK; AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.

Abstract

Antagonism of the chemokine receptor CXCR2 has been proposed as a strategy for the treatment of inflammatory diseases such as arthritis, chronic obstructive pulmonary disease and asthma. Earlier series of bicyclic CXCR2 antagonists discovered at AstraZeneca were shown to have low solubility and poor oral bioavailability. In this Letter we describe the design, synthesis and characterisation of a new series of monocyclic CXCR2 antagonists with improved solubility and good pharmacokinetic profiles.

KEYWORDS:

CXCR2; Chemokine antagonism; Inflammatory disease; Solubility

PMID:
25708618
DOI:
10.1016/j.bmcl.2015.01.067
[Indexed for MEDLINE]

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