1,6-Disubstituted indole derivatives as selective human neuronal nitric oxide synthase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Maddaford, Shawn¹  Renton, Paul¹  Speed, Joanne¹  Annedi, Subhash C.¹  Ramnauth, Jailall¹  Rakhit, Suman¹  Andrews, John¹  Mladenova, Gabriela¹  Majuta, Lisa²  Porreca, Frank² 

[1] NeurAxon Inc, Mississauga, ON L5K 1B3, Canada

[2] Univ Arizona, Dept Pharmacol, Tucson, AZ USA

关键词: 1,6-Disubstitued indole derivatives;    Nitric oxide;    Nitric oxide synthase;    Nitric oxide synthase inhibitors;    Selective neuronal nitric oxide synthase inhibitors;   

DOI  :  10.1016/j.bmcl.2011.07.042

来源: Elsevier

【 摘 要 】

A series of 1,6-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase (NOS). By varying the basic amine side chain at the 1-position of the indole ring, several potent and selective inhibitors of human neuronal NOS were identified. In general compounds with bulkier side chains displayed increased selectivity for nNOS over eNOS and iNOS isoforms. One of the compounds, (R)-8 was shown to reduce tactile hyperesthesia (allodynia) after oral administration (30 mg/kg) in an in vivo rat model of dural inflammation relevant to migraine pain. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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