7-Azaindole-3-acetic acid derivatives: potent and selective CRTh2 receptor antagonists.
High throughput screening identified a 7-azaindole-3-acetic acid scaffold as a novel CRTh2 receptor antagonist chemotype, which could be optimised to furnish a highly selective compound with good functional potency for inhibition of human eosinophil shape change in whole blood and oral bioavailability in the rat.
Sandham
David A
DA
Global Discovery Chemistry, Novartis Institutes of Biomedical Research, Horsham Research Centre, Horsham, West Sussex RH12 5AB, United Kingdom. david.sandham@novartis.com
Adcock
Claire
C
Bala
Kamlesh
K
Barker
Lucy
L
Brown
Zarin
Z
Dubois
Gerald
G
Budd
David
D
Cox
Brian
B
Fairhurst
Robin A
RA
Furegati
Markus
M
Leblanc
Catherine
C
Manini
Jodie
J
Profit
Rachael
R
Reilly
John
J
Stringer
Rowan
R
Schmidt
Alfred
A
Turner
Katharine L
KL
Watson
Simon J
SJ
Willis
Jennifer
J
Williams
Gareth
G
Wilson
Caroline
C
D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010539:Permeability; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C413877:1H-pyrrolo(2,3-b)pyridine-3-acetic acid; D000085:Acetates; D000893:Anti-Inflammatory Agents; D011725:Pyridines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor