STRUCTURE-ACTIVITY-RELATIONSHIPS OF AN ENDOTHELIN ETA RECEPTOR ANTAGONIST, 50-235, AND ITS DERIVATIVES

被引：17

作者：

MIHARA, SI ^{[1
]}

SAKURAI, K ^{[1
]}

NAKAMURA, M ^{[1
]}

KONOIKE, T ^{[1
]}

FUJIMOTO, M ^{[1
]}

机构：

[1] SHIONOGI & CO LTD,SHIONOGI RES LAB,5-12-4 SAGISU,FUKUSHIMA KU,OSAKA 553,JAPAN

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1993年 / 247卷 / 02期

关键词：

27-O-CAFFEOYL MYRICERONE (50-235); STRUCTURE-ACTIVITY RELATIONSHIP; ENDOTHELIN RECEPTOR ANTAGONIST; I-125]ENDOTHELIN-1 BINDING; CYTOSOLIC FREE CA(2+);

D O I：

10.1016/0922-4106(93)90081-J

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

27-O-Caffeoyl myricerone (50-235) is a nonpeptide endothelin receptor antagonist which is highly selective for the endothelin ET(A) receptor subtype. In order to determine which functional groups in 50-235 are essential for its activity, we examined the potencies of 50-235 and its derivatives to inhibit [I-125]endothelin-1 binding and endothelin-1-induced increase in the cytosolic Ca2+ concentration in rat aortic smooth muscle A7r5 cells. The results suggest that the 3-keto, 17-carboxyl and 27-caffeoyl groups in 50-235 are important for ET(A) receptor blocking activity. Modifications of the catechol ring of the 27-caffeoyl group influenced the affinity and the functional antagonist activity, but the effects were not parallel.

引用

页码：219 / 221

页数：3

共 50 条

[1] THE ENDOTHELIN ET(A) RECEPTOR-SPECIFIC EFFECT OF 50-235, A NONPEPTIDE ENDOTHELIN ANTAGONIST
MIHARA, S
FUJIMOTO, M
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1993, 246 (01): : 33 - 38
[2] STRUCTURE-ACTIVITY-RELATIONSHIPS OF ENDOTHELIN RECEPTOR AGONISTS AND ANTAGONISTS
DOHERTY, AM
CODY, WL
HE, X
DEPUE, PL
LEONARD, DM
DUDLEY, DT
RAPUNDALO, ST
HINGORANI, GP
PANEK, RL
MAJOR, TC
HILL, KE
FLYNN, MA
REYNOLDS, EE
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1992, 203 : 174 - MEDI
[3] Endothelin receptor antagonist triterpenoid, myriceric acid A, isolated from Myrica cerifera, and structure activity relationships of its derivatives
Sakurawi, K
Yasuda, F
Tozyo, T
Nakamura, M
Sato, T
Kikuchi, J
Terui, Y
Ikenishi, Y
Iwata, T
Takahashi, K
Konoike, T
Mihara, S
Fujimoto, M
CHEMICAL & PHARMACEUTICAL BULLETIN, 1996, 44 (02) : 343 - 351
[4] STRUCTURE-ACTIVITY-RELATIONSHIPS OF CYCLIC PENTAPEPTIDE ENDOTHELIN-A RECEPTOR ANTAGONISTS
FUKAMI, T
NAGASE, T
FUJITA, K
HAYAMA, T
NIIYAMA, K
MASE, T
NAKAJIMA, S
FUKURODA, T
SAEKI, T
NISHIKIBE, M
IHARA, M
YANO, M
ISHIKAWA, K
JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (21) : 4309 - 4324
[5] STRUCTURE-ACTIVITY-RELATIONSHIPS OF MONOCYCLIC ENDOTHELIN ANALOGS
HUNT, JT
LEE, VG
STEIN, PD
HEDBERG, A
LIU, ECK
MCMULLEN, D
MORELAND, S
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1991, 1 (01) : 33 - 38
[6] PROGESTERONE DERIVATIVES THAT BIND TO THE DIGITALIS RECEPTOR - STRUCTURE-ACTIVITY-RELATIONSHIPS
KIM, RS
LABELLA, FS
ZUNZA, H
ZUNZA, F
TEMPLETON, JF
MOLECULAR PHARMACOLOGY, 1980, 18 (03) : 402 - 405
[7] STRUCTURE-ACTIVITY-RELATIONSHIPS IN ANTAGONIST AND INVERSE AGONIST LIGANDS FOR THE BENZODIAZEPINE RECEPTOR
CODDING, PW
ROSZAK, AW
SRKARADZINSKA, MB
COOK, JM
HAGEN, TJ
ALLEN, MS
CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1995, 73 (04): : 499 - 512
[8] Search for surrogates: A study of endothelin receptor antagonist structure activity relationships
Raju, B
Okun, I
Stavros, F
Chan, MF
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (07) : 933 - 938
[9] STRUCTURE-ACTIVITY-RELATIONSHIPS OF BDB AND ITS MONOMETHYL AND DIMETHYL DERIVATIVES
BRONSON, ME
JIANG, W
DERUITER, J
CLARK, CR
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1995, 51 (2-3) : 477 - 479
[10] ANTIMITOTIC EFFECTS OF HYDROXYUREA AND ITS DERIVATIVES - STRUCTURE-ACTIVITY-RELATIONSHIPS
YU, RJ
VANSCOTT, EJ
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1974, 63 (03) : 279 - 283

← 1 2 3 4 5 →