Linked Life Data

17067801

Source:http://linkedlifedata.com/resource/pubmed/id/17067801

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-12-15
pubmed:abstractText
A new group of 3-(4-substituted-phenyl)-4-(4-methylsulfonamidophenyl)-2(5H)furanones in which the methylsulfonyl (MeSO(2)) COX-2 pharmacophore present in rofecoxib was replaced by a methanesulfonamido (MeSO(2)NH) moiety, and where the substituent at the para-position of the C-3 phenyl ring was simultaneously varied (H, F, Cl, Br, Me, OMe), were evaluated to determine the combined effects of steric and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. Structure-activity relationship (SAR) studies showed that compounds having a neutral (H), or electronegative halogen (F, Cl, Br), substituent at the para-position of the C-3 phenyl ring inhibited both COX-1 and COX-2 with COX-2 selectivity indexes in the 3.1-39.4 range. In contrast, compounds having an electron-donating Me or OMe substituent were selective inhibitors of COX-2 (COX-1 IC(50)>100 microM). These SAR data indicate the 3-aryl-4-(4-methylsulfonamidophenyl)-2(5H)furanone scaffold provides a suitable template to design COX inhibitors with variable COX-2 selectivity indexes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1056-61
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Synthesis and biological evaluation of methanesulfonamide analogues of rofecoxib: Replacement of methanesulfonyl by methanesulfonamido decreases cyclooxygenase-2 selectivity.
pubmed:affiliation
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta Edmonton, Alta., Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't