Source:http://linkedlifedata.com/resource/pubmed/id/18693017
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
17
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| pubmed:dateCreated |
2008-9-4
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| pubmed:abstractText |
In trials to preserve the pharmacological profile and improve the bioavailability via lipophilicity increment of baclofen 1 and searching for more potent and less toxic muscle relaxants and analgesics, nine substituted cyclic analogues of 1 were designed and synthesized. The target derivatives 5-(4-chlorophenyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one (11-19) were obtained through amide formation to the corresponding intermediates (2-10) followed by cyclization using acetic anhydride. The structures of the target compounds (11-19) were confirmed by IR, (1)H NMR, MS, and elemental analyses. The neuropharmacological activities of these lipophilic cyclic analogues (11-19) were assessed for their effects on motor activity, muscle relaxation, pain relief and impaired cognition, by intraperitoneal administration at a dose of 3mg/kg with reference to those of baclofen 1. Our results showed that compounds 11-14 are devoid of all of the tested pharmacological effects associated with 1. In all paradigms tested, undecyl, tridecyl, heptdec-8-enyl and benzyl substituted analogue derivatives (15, 16, 18, and 19) revealed a significant neurological activity being vividly favorable comparable with baclofen 1. 2-Benzyl-5-(4-chlorophenyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one derivative 19 is the most active candidate with high significant neurological potencies, while 5-(4-chlorophenyl)-2-(dec-8-enyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one derivative 17 displayed activity at relatively higher time interval. These results probe a new structurally distinct class incorporating 1,3-oxazepine nucleus as promising candidates as GABA(B) agonists for further investigations.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Baclofen,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/GABA-B Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazepines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-B
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1464-3391
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
16
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
7983-91
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:18693017-Animals,
pubmed-meshheading:18693017-Baclofen,
pubmed-meshheading:18693017-Cognition Disorders,
pubmed-meshheading:18693017-Cyclization,
pubmed-meshheading:18693017-Dose-Response Relationship, Drug,
pubmed-meshheading:18693017-Drug Design,
pubmed-meshheading:18693017-Drug Evaluation, Preclinical,
pubmed-meshheading:18693017-GABA Agonists,
pubmed-meshheading:18693017-GABA-B Receptor Agonists,
pubmed-meshheading:18693017-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:18693017-Injections, Intraperitoneal,
pubmed-meshheading:18693017-Magnetic Resonance Spectroscopy,
pubmed-meshheading:18693017-Male,
pubmed-meshheading:18693017-Mice,
pubmed-meshheading:18693017-Molecular Structure,
pubmed-meshheading:18693017-Motor Activity,
pubmed-meshheading:18693017-Muscle Relaxation,
pubmed-meshheading:18693017-Oxazepines,
pubmed-meshheading:18693017-Pain,
pubmed-meshheading:18693017-Receptors, GABA-B,
pubmed-meshheading:18693017-Reference Standards,
pubmed-meshheading:18693017-Stereoisomerism
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| pubmed:year |
2008
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| pubmed:articleTitle |
5-(4-Chlorophenyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one derivatives as lipophilic cyclic analogues of baclofen: design, synthesis, and neuropharmacological evaluation.
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| pubmed:affiliation |
Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. atef@aun.edu.eg
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| pubmed:publicationType |
Journal Article
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