Hit-to-lead studies: the discovery of potent, orally bioavailable triazolethiol CXCR2 receptor antagonists.
A Hit-to-Lead optimisation programme was carried out on the high throughput screening hit, the triazolethiol 1, resulting in the discovery of the potent, orally bioavailable triazolethiol CXCR2 receptor antagonist 45.
Baxter
Andrew
A
AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. andrew.jg.baxter@astrazeneca.com
Bennion
Colin
C
Bent
Janice
J
Boden
Kerry
K
Brough
Steve
S
Cooper
Anne
A
Kinchin
Elizabeth
E
Kindon
Nicholas
N
McInally
Tom
T
Mortimore
Mike
M
Roberts
Bryan
B
Unitt
John
J
D000284:Administration, Oral; D000818:Animals; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*
D018925:Chemokines; D023063:Receptors, Interleukin-8B; D014230:Triazoles