Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A POTENT NEW CLASS OF KAPPA-RECEPTOR AGONIST - 4-SUBSTITUTED 1-(ARYLACETYL)-2-[(DIALKYLAMINO)METHYL]PIPERAZINES
Autore:
NAYLOR A; JUDD DB; LLOYD JE; SCOPES DIC; HAYES AG; BIRCH PJ;
Indirizzi:
GLAXO GRP RES LTD,DEPT MED CHEM WARE SG12 0DJ HERTS ENGLAND GLAXO GRP RES LTD,DEPT NEUROPHARMACOL WARE SG12 0DJ HERTS ENGLAND
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 15, volume: 36, anno: 1993,
pagine: 2075 - 2083
SICI:
0022-2623(1993)36:15<2075:APNCOK>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
NALORPHINE-LIKE DRUGS; RABBIT VAS-DEFERENS; CHRONIC SPINAL DOG; OPIOID RECEPTORS; OPIATE RECEPTORS; MORPHINE-LIKE; DERIVATIVES; ANALGESICS; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
23
Recensione:
Indirizzi per estratti:
Citazione:
A. Naylor et al., "A POTENT NEW CLASS OF KAPPA-RECEPTOR AGONIST - 4-SUBSTITUTED 1-(ARYLACETYL)-2-[(DIALKYLAMINO)METHYL]PIPERAZINES", Journal of medicinal chemistry, 36(15), 1993, pp. 2075-2083

Abstract

The synthesis of 4-substituted 1-(arylacetyl)-2-[(alkylamino)methyl]piperazines (10-22, 26, 27, and 30-33) and their activities as kappa-opioid receptor agonists are described. This includes a range of 4-acyl and 4-carboalkoxy derivatives with the latter series showing the greatest kappa-agonist activity. In particular, methyl yl]-3-[(1-pyrrolidinyl)methyl]-1-piperazinecarboxy late (18) displays exceptional potency and selectivity. It showed the following activities in functional in vitro assays: rabbit vas deferens (kappa-specific tissue) IC50 = 0.041 nM, rat vas deferens (mu-specific tissue) IC50 > 10 000 nM, and hamster vas deferens (delta-specific tissue) IC50 > 10 000 nM. Compound 18 is also a highly potent antinociceptive agent, as determined in the mouse acetylcholine-induced abdominal constriction test: ED50 = 0.000 52 mg/kg, sc. The activity of 18 resides solely in its 3(R)-enantiomer. The kappa-agonist activity in both the 4-acyl and the 4-carbamate series is sensitive to the size of the 4-substituent. In addition, it wouldappear that an appreciable negative electrostatic potential in this region of the molecule is an important requirement for optimal

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 22:07:19