Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
3-DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS OF 5-HT RECEPTOR-BINDING DATA FOR TETRAHYDROPYRIDINYLINDOLE DERIVATIVES - A COMPARISON OF THE HANSCH AND COMFA METHODS
Autore:
AGARWAL A; PEARSON PP; TAYLOR EW; LI HB; DAHLGREN T; HERSLOF M; YANG YH; LAMBERT G; NELSON DL; REGAN JW; MARTIN AR;
Indirizzi:
UNIV ARIZONA,COLL MED,DEPT PHARMACOL & TOXICOL TUCSON AZ 85621 UNIV ARIZONA,COLL MED,DEPT PHARMACOL & TOXICOL TUCSON AZ 85621 UNIV GEORGIA,COLL PHARM,DEPT MED CHEM ATHENS GA 30602
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 25, volume: 36, anno: 1993,
pagine: 4006 - 4014
SICI:
0022-2623(1993)36:25<4006:3QSO5R>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOGNITION SITES; RU-24969; ANALOGS; FIELD; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
A. Agarwal et al., "3-DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS OF 5-HT RECEPTOR-BINDING DATA FOR TETRAHYDROPYRIDINYLINDOLE DERIVATIVES - A COMPARISON OF THE HANSCH AND COMFA METHODS", Journal of medicinal chemistry, 36(25), 1993, pp. 4006-4014

Abstract

A series of new derivatives of 3-(1,2,5,6-tetrahydropyridin-4-yl) indole (4-THPI) has been synthesized, and their dissociation constants atthe 5-HT1A and 5-HT2 serotonin (5-HT) receptor subtypes have been determined. The new data were combined with similar binding data on a related set of THPI analogs reported previously (Taylor et al. Mol. Pharmacol. 1988, 34, 42-53) and used to develop 3-dimensional quantitative structure-activity relationships (3-D QSARs) for these compounds at the 5-HT1A and 5-HT2 receptor sites, by the method of comparative molecular field analysis (CoMFA). Since the previous study included several conventional QSARs obtained by Hansch analysis, and the new compounds in some cases fall within the congeneric series used in those analyses, we were able to make a direct comparison of the predictive capabilities of CoMFA and Hansch analysis using identical training and test data sets. The overall quality of actual predictions of activity by both methods appears to be about the same, as assessed by the root mean square (rms) residuals between actual and predicted pK(i) values. On the one hand, the compounds most poorly predicted by the Hansch analysis were 34, 35, and 37, while compounds 30-33 were relative poorly predicted by CoMFA. However, a clear advantage of CoMFA is the ability to include diversely substituted or noncongeneric analogs that must be omitted from conventional QSAR analysis. Using the entire data set of 45 THPI analogs reported here, pK(i) predictions for six additional compounds having 5-heteroarylindole substituents gave rms residuals of 0.46 and 0.36 for the 5-HT1A and 5-HT2 models, respectively; this is close to the experimental error of the binding data. The significance of the CoMFA field graphs in terms of molecular features required for activity and selectivity at these 5-HT receptor subtypes is discussed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 14:59:35