Hit-to-Lead studies: the discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists.
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.
Baxter
Andrew
A
AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. andrew.jg.baxter@astrazeneca.com
Cooper
Anne
A
Kinchin
Elizabeth
E
Moakes
Kerry
K
Unitt
John
J
Wallace
Alan
A
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004353:Drug Evaluation, Preclinical / Q000379:methods; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D011743:Pyrimidines / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology*
D011743:Pyrimidines; D023063:Receptors, Interleukin-8B; D013844:Thiazoles