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Titolo:
DERIVATIVES OF (R)-5-FLUORO-8-HYDROXY-2-(DIPROPYLAMINO)TETRALIN AND (S)-5-FLUORO-8-HYDROXY-2-(DIPROPYLAMINO)TETRALIN - SYNTHESIS AND INTERACTIONS WITH 5-HT1A RECEPTORS
Autore:
HOOK BB; CORTIZO L; JOHANSSON AM; WESTLINDDANIELSSON A; MOHELL N; HACKSELL U;
Indirizzi:
UNIV UPPSALA,CTR BIOMED,BOX 574 S-75123 UPPSALA SWEDEN UNIV UPPSALA,CTR BIOMED S-75123 UPPSALA SWEDEN ASTRA ARCUS AB,PRECLIN R&D S-15185 SODERTALJE SWEDEN
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 20, volume: 39, anno: 1996,
pagine: 4036 - 4043
SICI:
0022-2623(1996)39:20<4036:DO(A(>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSTSYNAPTIC 5-HT(1A) RECEPTORS; SEROTONIN REUPTAKE INHIBITORS; ANTAGONIST (S)-UH-301; STEREOSELECTIVE INTERACTIONS; H-3 WAY-100635; SELECTIVE ANTAGONIST; RAT HIPPOCAMPUS; BRAIN; LIGANDS; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
72
Recensione:
Indirizzi per estratti:
Citazione:
B.B. Hook et al., "DERIVATIVES OF (R)-5-FLUORO-8-HYDROXY-2-(DIPROPYLAMINO)TETRALIN AND (S)-5-FLUORO-8-HYDROXY-2-(DIPROPYLAMINO)TETRALIN - SYNTHESIS AND INTERACTIONS WITH 5-HT1A RECEPTORS", Journal of medicinal chemistry, 39(20), 1996, pp. 4036-4043

Abstract

Analogs of the 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [(S)-1, (S)-UH301] have been prepared. The C8-substituent has been varied, and in some derivatives one of the N-propylgroups has been exchanged for a 4-(8-aza-7,9-dioxospiro[4.5]decan-8-yl)-butyl group. The novel. compounds have been evaluated for affinity to rat brain 5-HT1A receptors in competition experiments with [H-3]-8-OH-DPAT. In addition, the efficacy of the compounds was assessed by their ability to inhibit the VIP-stimulated cAMP formation in GH(4)ZD10 cells expressing rat 5-HT1A receptors. Varying degrees of intrinsic activity was revealed among the compounds tested, i.e., the profiles ranged from full agonists to antagonists. All R-enantiomers are characterized as full agonists at 5-HT1A receptors, whereas partial agonists orantagonists were found among the corresponding S-enantiomers. Substitution of one of the N-propyl groups for a 4-(8-aza-7,9-dioxospiro[4.5]decan-8-yl)butyl group seems to increase efficacy as well as affinity for 5-HT1A receptors. A favorable interaction with an accessory binding site by the N-4-(8-aza-7,9-dioxospiro[4.5]decan-8-yl)butyl group maycontribute to the increased affinity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 10:56:29