BALANCED AT(1) AND AT(2) ANGIOTENSIN-II ANTAGONISTS .3. POTENT AND ORALLY-ACTIVE 5-BETA-KETOSULFOXIDE IMIDAZOLYL BIPHENYL SULFONYLUREAS

被引：6

作者：

DEPREZ, P

GUILLAUME, J

CORBIER, A

VEVERT, JP

FORTIN, M

HECKMANN, B

机构：

[1] Roussel Uclaf, 93235 Romainville Cedex

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 22期

关键词：

D O I：

10.1016/0960-894X(95)00480-H

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the imidazolyl biphenyl sulfonylurea series, effects of substitution in position 5 of the imidazole ring with enolic ketone moiety were studied on AT(2) binding. beta-ketosulfoxide, beta-ketosulfone and beta-ketoester proved to be highly effective substituents for potent nanomolar binding affinity on both AT(1) and AT(2) receptor subtypes. This led to the identification of beta-ketophenylsulfoxide RU 64276 as a potent and orally active AT(1) antagonist and AT(2) binding inhibitor.

引用

页码：2617 / 2622

页数：6

共 20 条

[1]

ASHTON WT, 1994, EXPERT OPIN INV DRUG, V3, P1105

[2]

BUHLMAYER P, 1992, CURR OPIN THER PAT, V2, P1693

[3] 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

[4] TRIAZOLINONE BIPHENYLSULFONAMIDES AS ANGIOTENSIN-II RECEPTOR ANTAGONISTS WITH HIGH-AFFINITY FOR BOTH THE AT(1) AND AT(2) SUBTYPES [J].

CHANG, LL ;

ASHTON, WT ;

FLANAGAN, KL ;

CHEN, TB ;

OMALLEY, SS ;

ZINGARO, GJ ;

SIEGL, PKS ;

KIVLIGHN, SD ;

LOTTI, VJ ;

CHANG, RSL ;

GREENLEE, WJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (26) :4464-4478

[5] ORAL-ADMINISTRATION OF DUP-753, A SPECIFIC ANGIOTENSIN-II RECEPTOR ANTAGONIST, TO NORMAL-MALE VOLUNTEERS - INHIBITION OF PRESSOR-RESPONSE TO EXOGENOUS ANGIOTENSIN-I AND ANGIOTENSIN-II [J].

CHRISTEN, Y ;

WAEBER, B ;

NUSSBERGER, J ;

PORCHET, M ;

BORLAND, RM ;

LEE, RJ ;

MAGGON, K ;

SHUM, L ;

TIMMERMANS, PBMWM ;

BRUNNER, HR .

CIRCULATION, 1991, 83 (04) :1333-1342

[6]

CORVOL P, 1989, CLIN EXP HYPERTENS A, V11, P463

[7] SULFONYLUREAS AND SULFONYLCARBAMATES AS NEW NON-TETRAZOLE ANGIOTENSIN-II RECEPTOR ANTAGONISTS - DISCOVERY OF A HIGHLY POTENT ORALLY-ACTIVE (IMIDAZOLYLBIPHENYLYL) SULFONYLUREA (HR-720) [J].

DEPREZ, P ;

GUILLAUME, J ;

BECKER, R ;

CORBIER, A ;

DIDIERLAURENT, S ;

FORTIN, M ;

FRECHET, D ;

HAMON, G ;

HECKMANN, B ;

HEITSCH, H ;

KLEEMANN, HW ;

VEVERT, JP ;

VINCENT, JC ;

WAGNER, A ;

ZHANG, JD .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (13) :2357-2377

[8]

DEPREZ P, IN PRESS BIOORG ME 1

[9]

DEPREZ P, IN PRESS BIOORG ME 2

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

FERRARIO, CM .

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

← 1 2 →