Linked Life Data

2834557

Source:http://linkedlifedata.com/resource/pubmed/id/2834557

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1988-6-7
pubmed:abstractText
A series of 18 1-substituted 7-[3-[(ethylamino)methyl]-1- pyrrolidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinoline- carboxylic acids (N1 analogues of CI-934) were synthesized and evaluated for antibacterial activity and DNA-gyrase inhibition. Correlations between the inhibition of DNA gyrase and antibacterial potency were established. A quantitative structure-activity relationship (QSAR) was derived by using the antibacterial potency for each of 11 strains of bacteria and the Gram-negative mean. The equations indicated that antibacterial potency was strongly dependent on STERIMOL length and width and the level of unsaturation of the N1 substituent. Some strains also showed a dependence on the presence of heteroatoms (O, N, S) in the N1 group. No significant correlations between gyrase inhibition and combinations of these parameters were found. These QSAR results are discussed in conjunction with the conformational analyses from molecular modeling studies. The substituent that most enhanced the activity of the quinolone in all regards was the cyclopropyl group. This analogue, 1-cyclopropyl-7-[3-[(ethylamino)-methyl]-1-pyrrolidinyl]-6, 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (PD 117558), demonstrated outstanding broad spectrum activity both in vitro and in vivo when compared to relevant standards.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
991-1001
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
1-Substituted 7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-6,8- difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids. New quantitative structure-activity relationships at N1 for the quinolone antibacterials.
pubmed:affiliation
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
pubmed:publicationType
Journal Article