Linked Life Data

12479927

Source:http://linkedlifedata.com/resource/pubmed/id/12479927

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-12-13
pubmed:abstractText
Hydrogen bonding has been identified as an important parameter for describing drug permeability. Recently, we derived models for predicting intestinal permeability using the hydrogen bonding descriptors polar surface area (PSA) and number of hydrogen bond donors (HBD), and a lipophilicity descriptor [J. Med. Chem. 41 (1998) 4939]. We have now explored other types of hydrogen bonding descriptors to see if these improve the models. Both an experimental hydrogen bonding descriptor, deltalogP, and calculated descriptors, based either on semiempirical calculations or on experimentally derived hydrogen bond strength values of small molecules, were used. Principal component analyses (PCA) were performed in order to characterize the different parameters, using both a drug data set and a data set of small non-drug-like molecules for which deltalogP-values had been published. For a set of diverse drug molecules, for which human intestinal permeability data was available, a PLS-analysis was performed to study the correlation of permeability to the different hydrogen bonding parameters. No correlation could be identified between deltalogP and human intestinal permeability in this data set. However, the combination of a hydrogen bond donor descriptor, a general hydrogen bonding descriptor and a lipophilicity descriptor enabled the prediction of human intestinal permeability, whereas hydrogen bond acceptor descriptors were found to be less important. The obtained models successfully predicted the intestinal permeability values of two external data sets.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1093-3263
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-87
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Hydrogen bonding descriptors in the prediction of human in vivo intestinal permeability.
pubmed:affiliation
Department of Medicinal Chemistry, BMC, Uppsala University, SE-751 23 Uppsala, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't