Source:http://linkedlifedata.com/resource/pubmed/id/15540219
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2004-11-23
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| pubmed:abstractText |
Dipeptide analogues incorporating allophenylnorstatine [Apns; (2S,3S)-3amino-2-hydroxy-4-phenylbutyric acid] as a transition state mimic at the scissile bond were designed and synthesized in the hope of obtaining a novel KNI series of HIV protease inhibitors. The precursors, N-P2'-3-(2S,3S)-3-(tert-butyloxy-carbonyl)amino-2-hydroxy-4-phenylbutanoyl)-5,5-dimethylthiazolidine-4-carboxamide (N-Boc-Apns-Dmt-P2') 4a-p were prepared by deprotection of the synthones N-P2'-(tert-butyloxycarbonyl)-5,5-dimethylthiazolidine-4-carboxamide (Boc-Dmt-P2') 2a-p, then coupling with (2S,3S)3-(tert-butyloxycarbonyl)amino-2-hydroxy-4-phenylbutanoic acid (N-Boc-Apns-OH) 3. The deprotected intermediates 4 were coupled with the activated carboxyl groups of the P2 ligands to afford the target dipeptides. In this work, we fixed at the P2 site either a 2,6-dimethylphenoxyacetyl or a 3-hydroxy-2-methylbenzoyl group. Substitutes at the P2' site were varied to afford the members of the series 7 and 8. Improved activity of most of the members of series 8 relative to their analogues of series 7 can be partially attributed to the differences in the structures of the P2 moieties. Positional isomerism in the P2' moieties significantly affected the activity and polarity of the target.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0365-6233
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
337
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
587-98
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| pubmed:meshHeading | |
| pubmed:year |
2004
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| pubmed:articleTitle |
A novel dipeptide-based HIV protease inhibitor containing allophenylnorstatine.
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| pubmed:affiliation |
Pharmaceutical Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
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| pubmed:publicationType |
Journal Article
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