Linked Life Data

9207942

Source:http://linkedlifedata.com/resource/pubmed/id/9207942

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1997-8-7
pubmed:abstractText
Leflunomide is one of the most promising disease-modifying antirheumatic drug now in clinical trials for the treatment of rheumatoid arthritis. Metabolic studies have indicated that leflunomide is rapidly processed in vivo to an active metabolite, A771726 (2). To identify the chemical characteristics necessary for the immunosuppressive activity of 2, configurational and conformational studies were carried out on the latter and its inactive analogues (ethyl 3-hydroxy-2-((4-(trifluoromethyl)phenyl)carbamoyl)but-2-enoate, 3a, and 3-hydroxy-2-nitro-N-(4-(trifluoromethyl)phenyl)but-2-enamide, 3b). These studies suggested that the pharmacophore responsible for the immunosuppressive activity of 2 is a beta-keto amide with the enolic hydroxy group cis to the amidic moiety. To verify this hypothesis, a new class of immunosuppressive agents was designed and synthesized. Their testing in vitro and in vivo identified compounds which were more potent than both leflunomide and 2 and above all confirmed our hypothesis as to the key structural and chemical determinants for the immunosuppressive properties of 2 and our compounds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2011-6
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a potent immunosuppressive drug.
pubmed:affiliation
Italfarmaco Research Center, Milan, Italy.
pubmed:publicationType
Journal Article