Thienopyridines: nitric oxide synthase inhibitors with potent in vivo activity.
5-Substituted 7-amino-4,5-tetrahydrothieno[2,3-c]pyridines and 6-substituted 4-amino-6,7-dihydrothieno[3,2-c]pyridines were shown to be exceptionally potent inhibitors of inducible and neuronal nitric oxide synthase. Selectivity and potency could be modulated by variation of the 5- or 6-substituent. Compound 3e showed potent in vivo inhibition of iNOS.
Beaton
H
H
Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Loughborough, UK.
Boughton-Smith
N
N
Hamley
P
P
Ghelani
A
A
Nicholls
D J
DJ
Tinker
A C
AC
Wallace
A V
AV
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000819:agonists; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D019323:omega-N-Methylarginine / Q000494:pharmacology
D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009573:Nitrites; D011725:Pyridines; D019323:omega-N-Methylarginine; C496320:NOS1 protein, human; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat