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Titolo:
beta(3)-Adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-{[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acid
Autore:
Tanaka, N; Tamai, T; Mukaiyama, H; Hirabayashi, A; Muranaka, H; Ishikawa, T; Akahane, S; Akahane, M;
Indirizzi:
Kissei Pharmaceut Co Ltd, Cent Res Lab, Nagano 3998304, Japan Kissei Pharmaceut Co Ltd Nagano Japan 3998304 Lab, Nagano 3998304, Japan
Titolo Testata:
BIOORGANIC & MEDICINAL CHEMISTRY
fascicolo: 12, volume: 9, anno: 2001,
pagine: 3265 - 3271
SICI:
0968-0896(200112)9:12<3265:BAFTTO>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN BETA-3-ADRENERGIC RECEPTOR; PROLIFERATOR-ACTIVATED RECEPTOR; BETA(3) ADRENERGIC-RECEPTOR; ADRENOCEPTOR SUBTYPES; DETRUSOR MUSCLE; IN-VITRO; SELECTIVITY; EXPRESSION; RELAXATION; OBESITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Tanaka, N Kissei Pharmaceut Co Ltd, Cent Res Lab, 4365-1 Hotaka, Nagano 3998304, Japan Kissei Pharmaceut Co Ltd 4365-1 Hotaka Nagano Japan 3998304 pan
Citazione:
N. Tanaka et al., "beta(3)-Adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-{[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acid", BIO MED CH, 9(12), 2001, pp. 3265-3271

Abstract

In a search for novel analogues of beta (3)-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acids (1a-e), into which a fibrate-like structure ha been incorporated, were synthesised. Compound la was found to be a selective beta (3)-AR agonist in functional assays using the ferret detrusor (VAR), rat uterus (beta (2)-AR), and rat atrium (beta (1)-AR): beta (3): EC50 = 7.8 nM, beta (2): IC50 = 7,300 nM, beta (1): EC20 = 23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of la further improved VAR selectivity. In an in vivo study, la lowered intrabladder pressure (ED50 = 31 mug/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that la and its analogues (1b e), possess beta (3)-AR agonistic activity in the absence of undesirable beta (1)- or beta (2)-AR mediated actions. and may be useful for clinical treatment and pharmacological studies. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 15:16:27