Acyliminothiadiazoline derivatives: New, highly potent, and orally active angiotensin II receptor antagonists

被引：21

作者：

Hirata, T ^{[1
]}

Nomiyama, J ^{[1
]}

Sakae, N ^{[1
]}

Nishimura, K ^{[1
]}

Yokomoto, M ^{[1
]}

Inoue, S ^{[1
]}

Tamura, K ^{[1
]}

Okuhira, M ^{[1
]}

Amano, H ^{[1
]}

Nagao, Y ^{[1
]}

机构：

[1] UNIV TOKUSHIMA,FAC PHARMACEUT SCI,TOKUSHIMA 770,JAPAN

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 13期

关键词：

D O I：

10.1016/S0960-894X(96)00250-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Syntheses and pharmacological properties of a new series of acyliminothiadiazoline derivatives 1 are described. These compounds exhibited angiotensin II receptor antagonistic activities in vitro and in vivo. Among them, the compound 1g (KRH-594) showed the strongest antihypertensive action in renal hypertensive rats after oral administration, and its oral bioavailability in dogs was also found to be high (73%). Copyright (C) 1996 Elsevier Science Ltd

引用

收藏

页码：1469 / 1474

页数：6

相关论文

共 13 条

[1] NOMENCLATURE FOR ANGIOTENSIN RECEPTORS - A REPORT OF THE NOMENCLATURE-COMMITTEE OF THE COUNCIL-FOR-HIGH-BLOOD-PRESSURE-RESEARCH [J].

BUMPUS, FM ;

CATT, KJ ;

CHIU, AT ;

DEGASPARO, M ;

GOODFRIEND, T ;

HUSAIN, A ;

PEACH, MJ ;

TAYLOR, DG ;

TIMMERMANS, PBMWM .

HYPERTENSION, 1991, 17 (05) :720-721

[2] DISCOVERY OF A NOVEL CLASS OF ORALLY ACTIVE, NONPEPTIDE ANGIOTENSIN-II ANTAGONISTS [J].

DE, B ;

WINN, M ;

ZYDOWSKY, TM ;

KERKMAN, DJ ;

DEBERNARDIS, JF ;

LEE, J ;

BUCKNER, S ;

WARNER, R ;

BRUNE, M ;

HANCOCK, A ;

OPGENORTH, T ;

MARSH, K .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (20) :3714-3717

[3] THE DISCOVERY OF DUP-753, A POTENT, ORALLY ACTIVE NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONIST [J].

DUNCIA, JV ;

CARINI, DJ ;

CHIU, AT ;

JOHNSON, AL ;

PRICE, WA ;

WONG, PC ;

WEXLER, RR ;

TIMMERMANS, PBMWM .

MEDICINAL RESEARCH REVIEWS, 1992, 12 (02) :149-191

[4] THE RENIN-ANGIOTENSIN SYSTEM - IMPORTANCE IN PHYSIOLOGY AND PATHOLOGY [J].

FERRARIO, CM .

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1990, 15 :S1-S5

[5]

HIRATA T, IN PRESS HETEROCYCLE

[6] NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONISTS - SYNTHESIS AND BIOLOGICAL-ACTIVITY OF BENZIMIDAZOLES [J].

KUBO, K ;

INADA, Y ;

KOHARA, Y ;

SUGIURA, Y ;

OJIMA, M ;

ITOH, K ;

FURUKAWA, Y ;

NISHIKAWA, K ;

NAKA, T .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (12) :1772-1784

[7] PHARMACOLOGICAL PROFILE OF GR117289 INVITRO - A NOVEL, POTENT AND SPECIFIC NONPEPTIDE ANGIOTENSIN AT1 RECEPTOR ANTAGONIST [J].

ROBERTSON, MJ ;

BARNES, JC ;

DREW, GM ;

CLARK, KL ;

MARSHALL, FH ;

MICHEL, A ;

MIDDLEMISS, D ;

ROSS, BC ;

SCOPES, D ;

DOWLE, MD .

BRITISH JOURNAL OF PHARMACOLOGY, 1992, 107 (04) :1173-1180

[8]

SUPURAN C, 1992, REV ROUM CHIM, V14, P289

[9]

TIMMERMANS PBM, 1991, TREND PHARM SCI, V12, P25

[10]

TIMMERMANS PBMWM, 1993, PHARMACOL REV, V45, P205