Linked Life Data

8874041

Source:http://linkedlifedata.com/resource/pubmed/id/8874041

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3-4
pubmed:dateCreated
1997-2-3
pubmed:abstractText
From an initial mass screening lead, (IC50: 3 microM) and information derived from the X-ray crystallographic structure of a related analog, complexed with HIV protease (PR), the design of more potent inhibitors has been advanced. Various structure-guided approaches to fill P1' and P2' pockets using this pyran-2-one template, molecular modeling and X-ray crystallographic studies led to potent compounds. Of particular significance to the design of this series of inhibitors is the displacement of key structural waters. The binding modes of a series of pyran-2-one analogs and comparison of binding modes with different pyran-2-ones, are highlighted. Noteworthy was the discovery of a highly potent (IC50: 0.007 microM) pyran-2-one derivative, containing novel P1' and P2' functionalization and possessing no chiral centers and having low molecular weight. Pyran-2-ones possessing appended groups to reach to the S3 pocket of the enzyme via tethering on the 6-phenyl ring of pyran-2-one ring is also discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1055-9612
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15-28
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Nonpeptidic potent HIV-1 protease inhibitors.
pubmed:affiliation
Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48106-1047, USA.
pubmed:publicationType
Journal Article, Review