当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Novel, druglike 1,7-disubstituted 2,3,4,5-tetrahydro-1H-benzo[b]azepine-based selective inhibitors of human neuronal nitric oxide synthase (nNOS).

Novel, druglike 1,7-disubstituted 2,3,4,5-tetrahydro-1H-benzo[b]azepine-based selective inhibitors of human neuronal nitric oxide synthase (nNOS).

Abstract：

:A novel class of 1,7-disubstituted 2,3,4,5-tetrahydro-1H-benzo[b]azepine derivatives was designed, synthesized and evaluated as human nitric oxide synthase (NOS) inhibitors. Structure-activity relationship studies based on various basic amine side chains attached at the 1-position of the 2,3,4,5-tetrahydro-1H-benzo[b]azepine ring led to the identification of several potent and highly selective inhibitors (17, 18, 25, (±)-39, and (±)-40) of human neuronal NOS. The potential therapeutic application of one of these new selective nNOS inhibitors (17) was demonstrated in an in vivo spinal nerve ligation model of neuropathic pain, and various in vitro safety pharmacology studies such as the hERG K(+) channel inhibition assay and high throughput broad screen (minimal activity at 79 receptors/transporters/ion channels).

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Annedi SC,Ramnauth J,Cossette M,Maddaford SP,Dove P,Rakhit S,Andrews JS,Porreca F

doi

10.1016/j.bmcl.2012.02.004

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

2510-3

issue

7

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)00187-4

journal_volume

22

pub_type

杂志文章

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