Design and Synthesis of Insect Juvenile Hormone antagonists

昆虫保幼激素拮抗剂的设计与合成

基本信息

批准号：
09460029
负责人：
KUWANO Eiichi
金额：
$ 6.53万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09460029/
关键词：
juvenile hormone precocious metamorphosis imidazoles 3-pyridines 変態昆虫培養細胞

项目摘要

A large number of 1,5-disubstituted imidazoles and 3-(1-alkenyl)pyridines were prepared and evaluated for their activity to induce precocious metamorphosis in larvae of the silkworm, Bombyx mori, which is known to be caused by removal of the corpora allata or anti-juvenile hormone agents. 5-(2-Allyloxyphenyl)- 1 -octylimidazole and 5-(2-chlorophenyl)- 1 -octylimidazole showed relatively high activity. Neither methoprene, a juvenile hormone (JH) agonist, nor tebufenozide, an ecdysteroid agonist, could fully counteract precocious metamorphosis induced by high doses of each compound, but both hormone agonists were necessary for complete rescue. Among the 3-(1-alkenyl) pyridine derivatives tested, 3-(2-methyl-1-phenyl-1-propenyl) pyridine and 3-[(E)-7-(4-ethylphenoxy)-1-methyl-1-heptenyl] pyridine showed highest activity. Precocious metamorphosis induced by each compound was fully reversible by dietary administration of 20-hydroxyecdysone, indicating that these compounds temporarily depres … More s the ecdysteroid titer in the larval hemolymph to induce precocious metamorphosis. 1-[3-(4-Phenoxyphenoxy) propyl] imidazole (KS-175), which has two types of characteristic moieties of insect growth regulators (IGRs), a phenoxyphenoxyalkyl group of juvenile hormone analogs and an imidazole ring as a potent cytochrome P450 inhibitor, was synthesized and evaluated for its biological activity on the silkworm. KS-175 caused neither molting nor metamorphosis in the penultimate (4th) instar for more than 20 days when applied topically to the 4th instar larvae. This activity was different from any reported IGRs. After the treatment, ecdysteroid levels in hemolymph did not increase and the cells of the prothoracic gland had shrunk. When the treated 4th larvae were fed on artificial diet supplement with 20 ppm of 20-hydroxyecdysone, the larvae molted to the ultimate (5th) instar with a timing similar to that of control larvae. These results suggest that topical application of KS-175 irreversibly damages ecdysone biosynthesis in prothoracic glands. The growth of IPLB-Sf2l AE II insect cells was markedly promoted by a low concentration of methoprene, suggesting that this cell line may have a target site like receptor to recognize the JH followed by the promotion of cell proliferation. Less

制备了大量的1,5二取代的咪唑和3-（1-烷基烯基）吡啶的活性，并评估其活性，以诱导蚕的幼虫的早熟变形，Bombyx Mori，已知是由Collata andata andata或抗果毒果量的激素造成的。 5-（2-甲氧苯基）-1-辛基咪唑和5-（2-氯苯基）-1-辛基咪唑的活性相对较高。 Method -prene是一种幼马（JH）激动剂，也是ecdysteroid激动剂的Tebufenozide，可以完全抵消高剂量的每种化合物引起的早熟变质，但两种马酮激动剂都是完全营救的。在经过测试的3-（1-烷基）吡啶衍生物中，3-（2-甲基-1-苯基-1-丙苯酰）吡啶和3 - [（E）-7-（4-乙基苯氧基）-1-甲基-1-甲基-1-羟基甲基]吡啶的吡啶表现出最高活性。每种化合物诱导的早期变态是通过饮食中的20-羟基甲虫的饮食完全可逆的，这表明这些化合物暂时脱落……更多的是幼虫血淋巴中的ecdysteroid滴度，以诱导早产性变形。 1-[3-(4-Phenoxyphenoxy) propyl] imidazole (KS-175), which has two types of characteristic moieties of insulation growth regulators (IGRs), a phenoxyphenoxyalkyl group of juvenile hoormone analogs and an imidazole ring as a potential cytochrome P450 inhibitor, was synthesized and evaluated for its biologic activity on the silkworm.当局部应用于第四龄幼虫时，KS-175在倒数第二龄（第4）龄上既不引起蜕皮也不引起变态。该活动与任何报道的IGR不同。治疗后，血淋巴中的雌激素水平不会增加，而原质腺的细胞缩小了。当经过治疗的第四个幼虫以20 ppm的20 hydroxyecdysone喂食时，幼虫淋上了最终（第5）龄的幼虫，其时机与对照幼虫的时机相似。这些结果表明，局部应用KS-175不可逆地损害了原肌腺体中的Ecdysone生物合成。 IPLB-SF2L AE II昆虫细胞的生长通过低浓度的方法促进了明显的促进，这表明该细胞系可能具有像接收器这样的目标位点，以识别JH，然后促进细胞增殖。较少的