Abstract:
:Three soft drug analogs and a metabolite of methatropine based on phenylsuccinic structural moiety were synthesized and tested for activity. In an in vivo assay, the soft drugs were found to be two orders of magnitude less potent than methatropine while the carboxylate metabolite was found to be one order of magnitude less potent than the soft drugs. A structural isomer of compound 4a was found to be less potent. All the soft drugs tested elicited shorter durations of mydriatic action in rabbit eyes compared to atropine. The untreated eye was dilated in the atropine treated animals while no dilation occurred in the soft drug treated animals indicating facile systemic metabolism of the soft drugs to inactive moieties, possibly the carboxylate metabolite. In in vitro stability studies, the soft drugs have been found to be more hydrolytically labile than atropine. The shorter duration of mydriatic action of compound 4a coupled with increased hydrolytic lability make this a candidate for further study.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Hammer RH,Gunes E,Kumar GN,Wu WM,Srinivasan V,Bodor NSdoi
10.1016/s0968-0896(00)82119-7subject
Has Abstractpub_date
1993-09-01 00:00:00pages
183-7issue
3eissn
0968-0896issn
1464-3391pii
S0968-0896(00)82119-7journal_volume
1pub_type
杂志文章abstract::The chemistries of S-nitroso-DL-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) in relation to their ability to relax vascular smooth muscle and prevent platelet aggregation have been investigated. Metal ion catalysis greatly accelerates the decomposition of SNAP, but has little effect on GSNO. Instead, NO releas...
journal_title:Bioorganic & medicinal chemistry
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更新日期:2007-04-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2007.11.082
更新日期:2008-03-01 00:00:00
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