咪唑偕胺肟的合成、眼部效应及一氧化氮释放

Synthesis, ocular effects, and nitric oxide donation of imidazole amidoximes.

作者信息

Oresmaa L, Kotikoski H, Haukka M, Oksala O, Pohjala E, Vapaatalo H, Moilanen E, Vainiotalo P, Aulaskari P

机构信息

Department of Chemistry, University of Joensuu, PO Box 111, 80101 Joensuu, Finland.

出版信息

Eur J Med Chem. 2006 Sep;41(9):1073-9. doi: 10.1016/j.ejmech.2006.05.001. Epub 2006 Jun 9.

DOI:10.1016/j.ejmech.2006.05.001

PMID:16762462

Abstract

Novel 1-R-imidazole-5-amidoximes and 1-R-5-cyano-imidazole-4-amidoximes (R: H, Me, Bn) were prepared from their corresponding nitriles and were tested for their efficacy to lower intraocular pressure (IOP) in rabbits. The ability of these compounds to donate nitric oxide (NO) was studied by observing the stimulation of formation of cyclic guanosine-3',5'-monophosphate (cGMP) in the incubation of porcine iris-ciliary body. In the incubation experiments, 1-methylimidazole-5-amidoxime and 1(H)-imidazole-4(5)-amidoxime stimulated formation of cGMP indicating NO donating ability of these compounds. 1-Methylimidazole-5-amidoxime lowered IOP significantly after intravitreal injection.

摘要

新型1-R-咪唑-5-脒肟和1-R-5-氰基-咪唑-4-脒肟（R：H、Me、Bn）由其相应的腈制备而成，并对其降低兔眼内压（IOP）的功效进行了测试。通过观察猪虹膜睫状体孵育过程中环鸟苷-3',5'-单磷酸（cGMP）形成的刺激情况，研究了这些化合物释放一氧化氮（NO）的能力。在孵育实验中，1-甲基咪唑-5-脒肟和1(H)-咪唑-4(5)-脒肟刺激了cGMP的形成，表明这些化合物具有释放NO的能力。玻璃体内注射后，1-甲基咪唑-5-脒肟可显著降低眼内压。