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Titolo:
DIFFERENTIATION BETWEEN PARTIAL AGONISTS AND NEUTRAL 5-HT1B ANTAGONISTS BY CHEMICAL MODULATION OF PYL]-4-HYDROXY-N-[4-(PYRIDIN-4-YL)PHENYL]BENZAMIDE (GR-55562)
Autore:
LAMOTHE M; PAUWELS PJ; BELLIARD K; SCHAMBEL P; HALAZY S;
Indirizzi:
CTR RECH PIERRE FABRE,DIV MED CHEM,17 AVE JEAN MOULIN F-81106 CASTRESFRANCE CTR RECH PIERRE FABRE,DIV MED CHEM F-81106 CASTRES FRANCE CTR RECH PIERRE FABRE,DEPT CELLULAR & MOL BIOL F-81106 CASTRES FRANCE CTR RECH PIERRE FABRE,DEPT ANALYT CHEM F-81106 CASTRES FRANCE
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 22, volume: 40, anno: 1997,
pagine: 3542 - 3550
SICI:
0022-2623(1997)40:22<3542:DBPAAN>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLONED HUMAN 5-HT1D-ALPHA; RECEPTOR; SEROTONIN; CLASSIFICATION; MECHANISMS; SUBFAMILY; MIGRAINE; BINDING; GENES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
28
Recensione:
Indirizzi per estratti:
Citazione:
M. Lamothe et al., "DIFFERENTIATION BETWEEN PARTIAL AGONISTS AND NEUTRAL 5-HT1B ANTAGONISTS BY CHEMICAL MODULATION OF PYL]-4-HYDROXY-N-[4-(PYRIDIN-4-YL)PHENYL]BENZAMIDE (GR-55562)", Journal of medicinal chemistry, 40(22), 1997, pp. 3542-3550

Abstract

The synthesis and binding affinity at cloned h5-HT1B, h5-HT1D, and h5-HT1A receptors of 3-[3-(NN-dimethylamino)propyl]-4-hydroxy-N-[4- (2, GR-55562) and four 0-methylated analogs are described. The functional activity of these compounds was determined at the h5-HT1B receptor using a [S-35]GTP gamma S binding assay. The four analogs have been prepared in order to evaluate the influence of the alkylamino side chain conformation on binding and intrinsic activity. Whereas 2 and its derivatives display a similar binding affinity profile, major differences arise from analysis of the intrinsic activity data at h5-HT1B receptors. The 0-methylated analog of 2, pyl]-4-methoxy-N-[4-(pyridin-4-yl)phenyl]benzamide (3a), and the (1Z)-3-(N,N-dimethylamino)prop-1-enyl derivative (3c) act as neutral and potent antagonists (in a similar way to 2), while the 3-(N,N-dimethylamino)-prop-1-ynyl(3b) and(1E)-3-(N,N-dimethylamino)prop-1-enyl(3d) analogs display nonnegligible agonist activity. Molecular modeling studies show that, when the common triaryl portions of the molecules are overlapped, the partial agonists and the neutral antagonists differ by a near-orthogonal orientation of the NH- projection to the hydrogen-bend receptor site.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 04:17:00