Heteroalicyclic carboxamidines as inhibitors of inducible nitric oxide synthase; the identification of (2R)-2-pyrrolidinecarboxamidine as a potent and selective haem-co-ordinating inhibitor.
| Autor: | Young RJ; GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Rob.J.Young@gsk.com, Alderton W, Angell AD, Beswick PJ, Brown D, Chambers CL, Crowe MC, Dawson J, Hamlett CC, Hodgson ST, Kleanthous S, Knowles RG, Russell LJ, Stocker R, Woolven JM |
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| Jazyk: | angličtina |
| Zdroj: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 May 15; Vol. 21 (10), pp. 3037-40. Date of Electronic Publication: 2011 Mar 21. |
| DOI: | 10.1016/j.bmcl.2011.03.038 |
| Abstrakt: | Heteroalicyclic carboxamidines were synthesised and evaluated as inhibitors of nitric oxide synthases. (2R)-2-Pyrrolidinecarboxamidine, in particular, was shown to be a highly potent in vitro (IC(50)=0.12 μM) and selective iNOS inhibitor (>100-fold vs both eNOS and nNOS), with probable binding to the key anchoring glutamate residue and co-ordination to the haem iron. (Copyright © 2011 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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