ORALLY-ACTIVE, NONPEPTIDE VASOPRESSIN V(1) ANTAGONISTS - A NOVEL SERIES OF 1-(1-SUBSTITUTED 4-PIPERIDYL)-3,4-DIHYDRO-2(1H)-QUINOLINONE

被引：36

作者：

OGAWA, H

YAMAMURA, Y

MIYAMOTO, H

KONDO, K

YAMASHITA, H

NAKAYA, K

CHIHARA, T

MORI, T

TOMINAGA, M

YABUUCHI, Y

机构：

[1] Second Institute of New Drug Research, Otsuka Pharmaceutical Co., Tokushima 771-01, 463-10 Kagasuno, Kawauchi-cho

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 14期

关键词：

D O I：

10.1021/jm00066a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of compounds has been synthesized and demonstrated to be antagonists of V1 receptors both in vitro and in vivo. These compounds are structurally related to the 1-(4-piperidyl)-2(1H)-quinolinones, including OPC-21268, an orally bioavailable AVP V1 antagonist with high V1 specificity. It has been found that the introduction of an acetamide group on the terminal alkoxy chain of 41-44 leads to an increase in oral activity. Certain of these compounds may have efficacy in the study of AVP V1 receptors.

引用

页码：2011 / 2017

页数：7

共 20 条

[1]

ADACHI M, 1985, CHEM PHARM BULL, V33, P1826

[2] POTENT VASOPRESSIN ANTAGONISTS LACKING THE PROLINE RESIDUE AT POSITION-7 [J].

ALI, FE ;

BRYAN, W ;

CHANG, HL ;

HUFFMAN, WF ;

MOORE, ML ;

HECKMAN, G ;

KINTER, LB ;

MCDONALD, J ;

SCHMIDT, D ;

SHUE, D ;

STASSEN, FL .

JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (06) :984-988

[3]

DUBB J, 1987, KIDNEY INT, V31, P267

[4] NOVEL VASOPRESSIN ANALOGS THAT HELP DEFINE A MINIMUM EFFECTIVE ANTAGONIST PHARMACOPHORE [J].

HUFFMAN, WF ;

ALI, FE ;

BRYAN, WM ;

CALLAHAN, JF ;

MOORE, ML ;

SILVESTRI, JS ;

YIM, NCF ;

KINTER, LB ;

MCDONALD, JE ;

ASHTONSHUE, D ;

STASSEN, FL ;

HECKMAN, GD ;

SCHMIDT, DB ;

SULAT, L .

JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (12) :1759-1760

[5] SYNTHESIS OF 1-(PIPERIDINYL-4)-INDOLINONES-(2) AND -3,4-DIHYDROCARBOSTYRILES - POTENTIAL ANALGESIC DRUGS .3. [J].

KLEIN, W ;

BACK, W ;

MUTSCHLER, E .

ARCHIV DER PHARMAZIE, 1974, 307 (05) :360-366

[6] [1-(BETA-MERCAPTO-BETA,BETA-CYCLOPENTAMETHYLENEPROPIONIC ACID),2-(O-METHYL)TYROSINE]ARGININE-VASOPRESSIN AND [1-(BETA-MERCAPTO-BETA,BETA-CYCLOPENTAMETHYLENEPROPIONIC ACID)]ARGININE-VASOPRESSIN, 2 HIGHLY POTENT ANTAGONISTS OF THE VASOPRESSOR RESPONSE TO ARGININE-VASOPRESSIN [J].

KRUSZYNSKI, M ;

LAMMEK, B ;

MANNING, M ;

SETO, J ;

HALDAR, J ;

SAWYER, WH .

JOURNAL OF MEDICINAL CHEMISTRY, 1980, 23 (04) :364-368

[7] SYNTHESIS OF ARGININE-VASOPRESSINS, MODIFIED IN POSITION-1 AND POSITION-2, AS ANTAGONISTS OF THE VASOPRESSOR RESPONSE TO THE PARENT HORMONE [J].

LAMMEK, B ;

REKOWSKI, P ;

KUPRYSZEWSKI, G ;

MELIN, P ;

RAGNARSSON, U .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (03) :603-606

[8]

LASZLO FA, 1991, PHARMACOL REV, V43, P73

[9] SYNTHESIS AND SOME PHARMACOLOGICAL PROPERTIES OF 18 POTENT O-ALKYLTYROSINE-SUBSTITUTED ANTAGONISTS OF THE VASOPRESSOR RESPONSES TO ARGININE-VASOPRESSIN [J].

MANNING, M ;

LAMMEK, B ;

BANKOWSKI, K ;

SETO, J ;

SAWYER, WH .

JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (10) :1485-1491

[10] CARBOXY TERMINUS OF VASOPRESSIN REQUIRED FOR ACTIVITY BUT NOT BINDING [J].

MANNING, M ;

OLMA, A ;

KLIS, W ;

KOLODZIEJCZYK, A ;

NAWROCKA, E ;

MISICKA, A ;

SETO, J ;

SAWYER, WH .

NATURE, 1984, 308 (5960) :652-653

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