A NOVEL CLASS OF PLATELET-ACTIVATING-FACTOR (PAF) ANTAGONISTS .2. MODIFICATION OF THE 2-POSITION OF THE GLYCEROL BACKBONE OF PAF-SULFONAMIDE ISOSTERES

被引：0

作者：

TSURI, T ^{[1
]}

MATSUI, T ^{[1
]}

HAGA, N ^{[1
]}

KAMATA, S ^{[1
]}

HAGISHITA, S ^{[1
]}

TAKAHASHI, K ^{[1
]}

KAKUSHI, H ^{[1
]}

UCHIDA, K ^{[1
]}

HATAKEYAMA, H ^{[1
]}

KUROSAWA, A ^{[1
]}

机构：

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

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 1992年 / 40卷 / 01期

关键词：

PLATELET ACTIVATING FACTOR; RECEPTOR ANTAGONIST; PLATELET ACTIVATING FACTOR-SULFONAMIDE ISOSTERE; OPTICALLY ACTIVE ENANTIOMER; ENANTIOSELECTIVITY; PLATELET AGGREGATION; PLATELET ACTIVATING FACTOR-INDUCED LETHALITY;

D O I：

暂无

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In a continuing effort to obtain more potent platelet activating factor (PAF) antagonists, we tried to synthesize a series of PAF-sulfonamide isosteres in which the substituent at the 2-position was modified to an acetoxy equivalent other than the methoxy group. These modifications produced highly active PAF antagonists. Compound 3-[2-(5-methyl-2H-tetrazol-2-yl)-3-(octadecylcarbamoyloxy)propylaminosulfonyl]propylquinolinium iodide (52) showed the most potent activity in the in vitro inhibitory effect on PAF-induced platelet aggregation in rabbit platelet-rich plasma (IC50 = 125 nM) and also in the in vivo protective effect on PAF-induced lethality in mice, with prolonged duration of action. Optically active enantiomers of this compound were synthesized and the (S)-(-)-isomer (IC50 = 87 nM) was found to be three times more potent that the (R)-(+)-isomer (IC50 = 289 nM), clearly exemplifying the enantioselectivity in the PAF-antagonist action of this novel compound.

引用

页码：85 / 95

页数：11

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