SYNTHESES AND PLATELET-AGGREGATION INHIBITORY AND ANTITHROMBOTIC PROPERTIES OF [2-[(OMEGA-AMINOALKOXY)PHENYL]ETHYL]BENZENES

被引：56

作者：

KIKUMOTO, R ^{[1
]}

HARA, H ^{[1
]}

NINOMIYA, K ^{[1
]}

OSAKABE, M ^{[1
]}

SUGANO, M ^{[1
]}

FUKAMI, H ^{[1
]}

TAMAO, Y ^{[1
]}

机构：

[1] MITSUBISHI KASEI CORP,RES CTR,PHARMACEUT LAB,1000 KAMOSHIDA CHO,MIDORI KU,YOKOHAMA,JAPAN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 06期

关键词：

D O I：

10.1021/jm00168a043

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of [2-[(⍵-aminoalkoxy)phenyl] ethyl] benzene derivatives were synthesized and evaluated for their ability to inhibit collagen-induced platelet aggregation in vitro and to protect experimental thrombosis in mice. The results showed that the compounds were in vitro inhibitors of collagen-induced platelet aggregation. Most of them were also effective in the mouse antithrombotic assay. The compounds were found to be potent antagonists to S2 serotonergic receptor, and good correlation (r = 0.85) between their S2 serotonergic receptor antagonism and their potency as platelet antiaggregatory drugs was observed. Among the compounds studied, mono[2-(dimethylamino)-l-[[2-[2-(3-methoxyphenyl) ethyl] phenoxy] methyl] ethyl] succinate hydrochloride (12b, MCI-9042) was selected for further pharmacological and toxicological evaluation. © 1990, American Chemical Society. All rights reserved.

引用

页码：1818 / 1823

页数：6

共 25 条

[11]

FINNEY DJ, 1961, PROBIT ANAL, P236

[12] UBER DIE DARSTELLUNG AROMATISCHER POLYHYDROXYVERBINDUNGEN UND POLYHYDROXYCARBONSAUREN .5. MONOFUNKTIONELLE UND BIFUNKTIONELLE TRIPHENYLPENYLPHOSPHONIUMSALZE [J].

FRIEDRICH, K ;

HENNING, HG .

CHEMISCHE BERICHTE-RECUEIL, 1959, 92 (11) :2756-2760

[13]

HLADOVEC J, 1986, THROMB RES, V41, P665, DOI 10.1016/0049-3848(86)90363-4

[14] SYNTHESIS AND ANTI-DEPRESSANT ACTIVITY OF SUBSTITUTED (OMEGA-AMINOALKOXY)BENZENE DERIVATIVES [J].

KIKUMOTO, R ;

TOBE, A ;

TONOMURA, S .

JOURNAL OF MEDICINAL CHEMISTRY, 1981, 24 (02) :145-148

[15] SYNTHESIS AND ANTI-ANXIETY ACTIVITY OF (OMEGA-PIPERAZINYLALKOXY)INDAN DERIVATIVES [J].

KIKUMOTO, R ;

TOBE, A ;

FUKAMI, H ;

EGAWA, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1983, 26 (02) :246-250

[16] SUBSTITUTED (OMEGA-AMINOALKOXY)STILBENE DERIVATIVES AS A NEW CLASS OF ANTICONVULSANTS [J].

KIKUMOTO, R ;

TOBE, A ;

FUKAMI, H ;

NONOMIYA, K ;

EGAWA, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1984, 27 (05) :645-649

[17]

KOCHWESER J, 1978, NEW ENGL J MED, V298, P1403

[18]

LEYSEN JE, 1982, ARCH INT PHARMACOD T, V256, P301

[19] RECEPTOR-BINDING PROFILE OF R-41-468, A NOVEL ANTAGONIST AT 5-HT2 RECEPTORS [J].

LEYSEN, JE ;

AWOUTERS, F ;

KENNIS, L ;

LADURON, PM ;

VANDENBERK, J ;

JANSSEN, PAJ .

LIFE SCIENCES, 1981, 28 (09) :1015-1022

[20]

Leysen L., 1985, SEROTONIN CARDIOVASC, P43

← 1 2 3 →