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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5145
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pubmed:dateCreated |
1994-2-10
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pubmed:abstractText |
Mechanistic information and structure-based design methods have been used to design a series of nonpeptide cyclic ureas that are potent inhibitors of human immunodeficiency virus (HIV) protease and HIV replication. A fundamental feature of these inhibitors is the cyclic urea carbonyl oxygen that mimics the hydrogen-bonding features of a key structural water molecule. The success of the design in both displacing and mimicking the structural water molecule was confirmed by x-ray crystallographic studies. Highly selective, preorganized inhibitors with relatively low molecular weight and high oral bioavailability were synthesized.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0036-8075
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pubmed:author |
|
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
263
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
380-4
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pubmed:dateRevised |
2007-3-19
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pubmed:meshHeading |
pubmed-meshheading:8278812-Administration, Oral,
pubmed-meshheading:8278812-Animals,
pubmed-meshheading:8278812-Azepines,
pubmed-meshheading:8278812-Binding Sites,
pubmed-meshheading:8278812-Biological Availability,
pubmed-meshheading:8278812-Cell Line,
pubmed-meshheading:8278812-Crystallography, X-Ray,
pubmed-meshheading:8278812-Dogs,
pubmed-meshheading:8278812-Drug Design,
pubmed-meshheading:8278812-Drug Evaluation, Preclinical,
pubmed-meshheading:8278812-HIV Protease,
pubmed-meshheading:8278812-HIV Protease Inhibitors,
pubmed-meshheading:8278812-HIV-1,
pubmed-meshheading:8278812-Hydrogen Bonding,
pubmed-meshheading:8278812-Models, Molecular,
pubmed-meshheading:8278812-Molecular Conformation,
pubmed-meshheading:8278812-Molecular Weight,
pubmed-meshheading:8278812-Rats,
pubmed-meshheading:8278812-Recombinant Proteins,
pubmed-meshheading:8278812-Urea,
pubmed-meshheading:8278812-Virus Replication
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pubmed:year |
1994
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pubmed:articleTitle |
Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors.
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pubmed:affiliation |
Department of Virology Research, DuPont Merck Pharmaceutical Company, Wilmington, DE 19880.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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