Linked Life Data

20015013

Source:http://linkedlifedata.com/resource/pubmed/id/20015013

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-19
pubmed:abstractText
Using computer-assisted combinatorial chemistry techniques, we have designed a virtual library of anti-influenza agents, analogs of inhibitor A-315675, containing a novel pyrrolidine core, which effectively inhibits both wild type and common oseltamivir-resistant mutant forms of the neuraminidase (NA) subtype N1 of avian influenza virus H5N1. A target-specific Potential of Mean Force (PMF) scoring function parameterized on a training set of 13 known pyrrolidine-based inhibitors of NA and validated on 3 others was used to predict the N1 inhibition constants for the focused library of A-315675 analogs. Nine virtual hits (best pyrrolidine inhibitors designed in the present study) are predicted to exhibit inhibition constants in the low picomolar range, up to 200 fold lower than the parent inhibitor A-315675 while displaying favorable predicted ADME-related properties. Proposed small highly-focused combinatorial subsets composed of R-groups most frequently occurring in the 200 most active analogs can be useful as a guide for synthetic and medicinal chemists who are developing a new generation of drugs against the avian influenza virus H5N1 by focusing their attention to this small portion of the chemical space.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1875-5402
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
268-77
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Combinatorial design of avian influenza neuraminidase inhibitors containing pyrrolidine core with a reduced susceptibility to viral drug resistance.
pubmed:affiliation
International Centre for Science and High Technology, UNIDO, AREA Science Park, Padriciano 99, Trieste I-34012, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't