Hit-to-Lead studies: the discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists

Andrew Baxter; Anne Cooper; Elizabeth Kinchin; Kerry Moakes; John Unitt; Alan Wallace

doi:10.1016/j.bmcl.2005.10.091

Hit-to-Lead studies: the discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists

Bioorg Med Chem Lett. 2006 Feb 15;16(4):960-3. doi: 10.1016/j.bmcl.2005.10.091. Epub 2005 Nov 15.

Authors

Andrew Baxter¹, Anne Cooper, Elizabeth Kinchin, Kerry Moakes, John Unitt, Alan Wallace

Affiliation

¹ AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. andrew.jg.baxter@astrazeneca.com

PMID: 16297626
DOI: 10.1016/j.bmcl.2005.10.091

Abstract

A Hit-to-Lead optimisation programme was carried out on a high throughput screening hit, the thiazolopyrimidine 1, resulting in the discovery of the potent, orally bioavailable CXCR2 antagonist 29.

MeSH terms

Administration, Oral
Animals
Biological Availability
Drug Evaluation, Preclinical / methods
Hepatocytes / drug effects
Hepatocytes / metabolism
Humans
In Vitro Techniques
Microsomes / drug effects
Microsomes / metabolism
Molecular Structure
Pyrimidines / administration & dosage*
Pyrimidines / chemical synthesis
Pyrimidines / pharmacology*
Rats
Receptors, Interleukin-8B / antagonists & inhibitors*
Structure-Activity Relationship
Thiazoles / administration & dosage*
Thiazoles / chemical synthesis
Thiazoles / pharmacology*

Substances

Pyrimidines
Receptors, Interleukin-8B
Thiazoles