Linked Life Data

21449619

Source:http://linkedlifedata.com/resource/pubmed/id/21449619

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2011-5-5
pubmed:abstractText
A number of pharmaceutically important drugs contain asymmetric sulfinyl moieties, so the biological evaluation of chiral sulfoxides as human drug metabolites is important for the development of safe and effective pharmaceuticals. Asymmetric oxidation is one of the most attractive ways to prepare chiral sulfoxides. In combination with different chiral ligands, the iron- and titanium-catalyzed asymmetric oxidations of tri- and tetrasubstituted 2-thioimidazoles afford the corresponding sulfoxides with enantiomeric excesses up to 99% as novel p38? mitogen-activated protein kinase (p38? MAPK) inhibitors. The enantiomerically pure sulfoxides were evaluated on their inhibitory potency against p38? MAPK compared to the respective sulfides and sulfoxide racemates and showed differences in their affinities for the enzyme with IC(50) in the low nanomolar range. In addition, the ability to inhibit the release of tumor necrosis factor-? (TNF-?) from human whole blood (HWB) was examined. Some pyridinylimidazole derivatives showed excellent HWB activity with IC(50) as low as 52 nM.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3283-97
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Chiral sulfoxides as metabolites of 2-thioimidazole-based p38? mitogen-activated protein kinase inhibitors: enantioselective synthesis and biological evaluation.
pubmed:affiliation
Department of Pharmaceutical/Medicinal Chemistry, Eberhard-Karls-University Tu?bingen, Auf der Morgenstelle 8, 72076 Tu?bingen, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't