Structure-Activity Relationship in Nematocidal Activity of Piperamides and Malabaricones

哌酰胺和马拉巴酮杀线虫活性的构效关系

基本信息

批准号：
06672096
负责人：
KIUCHI Fumiyuki
金额：
$ 0.38万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Seventy six piperamides and their analogs with twenty malabaricones and their analogs were synthesized and their nematocidal activity against second-stage larvae of dog roundworm, Toxocara canis, were examined. Among the piperamide analogs, the activity was largely dependent on the length of the alkyl chain and the nature of the amine moiety. The alkyl chain length which showed the strongest activity in a series of homologues were m=9 for the pyrrolidine amides and m=11 for the N-methylpiperazine amides. Calculated log P values of the activity of these compounds.Among the naturally occurring malabaricones which have two oxygen functions at both o-and o'-positions of the acetophenone moiety, malabaricone A showed the strongest activity. Among the synthetic malabaricone analogs without any substituent on the aryl moiety, at least one free hydroxy group was essential for the activity. A hydroxy group at the ortho position or at the benzylic position (introduced by reduction of the ketone or conjugation with the hydroxy group on the benzene ring) of the acetophenone moiety seemed to be important for the activity.

对76种载酰胺及其类似物的类似物进行了二十个马拉巴里酮及其类似物的合成，并检查了其对狗round虫的二阶段幼虫的杀死活性，Toxocara canis。在载酰胺类似物中，活性在很大程度上取决于烷基链的长度和胺基部分的性质。在一系列同源物中表现出最强活性的烷基链长对于吡咯烷酰胺为M = 9，而N-甲基哌嗪酰胺为M = 11。计算出这些化合物活性的log p值。在天然存在的马拉巴酮中，马拉巴里酮A均具有两个氧气和乙二醇部分的O'I-position，Malabaricone A显示出最强的活性。在芳基部分没有任何取代基的合成马拉巴酮类似物中，至少一个游离羟基对于活性至关重要。位于乙烯酮部分的Ortho位置或位于苯基位置的羟基或在苯二酮位置（通过还原酮或与苯环上的羟基的结合引入）似乎对活性很重要。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fumiyuki Kiuchi 他: "Nematocidal Activity of Malabaricones and Their Analogs on Second-stage Larvae of Toxocara canis" Chemical and Pharmaceutical Bulletin. in preparation.

Fumiyuki Kiuchi 等人：“马拉巴里酮及其类似物对犬弓蛔虫第二阶段幼虫的杀线虫活性”化学和药物通报正在准备中。

DOI：
发表时间：
期刊：
影响因子：
0
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通讯作者：

Fumiyuki Kiuchi, Norio Nakamura, Makiko Saitho, Kazue Komagome, Hirokuni Hiramatu, Noriaki Takimoto, Nobuaki Akao, Kaoru Kondo, Yoshisuke Tsuda: "Synthesis and Nematocidal Activity of Piperamides and Their Analogs on Second-stage Larvae of Toxocara canis"

Fumiyuki Kiuchi、Norio Nakamura、Makiko Saitho、Kazue Komagome、Hirokuni Hiramatu、Noriaki Takimoto、Nobuaki Akao、Kaoru Kondo、Yoshisuke Tsuda：“哌酰胺及其类似物对犬弓蛔虫第二阶段幼虫的合成和杀线虫活性”