title: Thienopyridines: nitric oxide synthase inhibitors with potent in vivo activity.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Loughborough, UK.
authors.forename: H
authors.initials: H
authors.lastname: Beaton
authors.forename: N
authors.initials: N
authors.lastname: Boughton-Smith
authors.forename: P
authors.initials: P
authors.lastname: Hamley
authors.forename: A
authors.initials: A
authors.lastname: Ghelani
authors.forename: D J
authors.initials: DJ
authors.lastname: Nicholls
authors.forename: A C
authors.initials: AC
authors.lastname: Tinker
authors.forename: A V
authors.initials: AV
authors.lastname: Wallace
mesh_terms: 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
chemical_list: 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