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Chemistry and biology of novel amine fungicides: Attempts to improve the antifungal activity of fenpropimorph

机译:新型胺类杀菌剂的化学和生物学:提高芬丙吗啉抗真菌活性的尝试

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AbstractIn spite of considerable efforts by many workers, there has been a lack of progress in the area of amine fungicides since fenpropimorph. Random synthesis of a large variety of different amine compounds, as well as intelligent structural modification of the lead structure fenpropimorph (well over 15 000 amines have been screened at BASF alone) have not led to a new market product so far. Further work has been focused on the reported mode of action of fenpropimorph, notably on the inhibition of the sterol Δ14‐reductase. Although some doubt has to be cast on the hypothesis that fenpropimorph behaves as a sterol mimic, the concept of ‘high energy intermediate’ inhibitors has been employed successfully. Rational drug design of azasterol mimics has led to a number of very potent inhibitors of the sterol Δ14‐reductase which also displayed high fungicidal activity in the greenhouse. Although many of these compounds are more powerful reductase inhibitors than fenpropimorph, under field conditions none showed significant advantages over this established fungicide.Most likely, fenpropimorph already exhibits the maximum fungicidal activity which can be attained by blocking the sterol Δ14‐reductase. This would mean that, with the development of the ‘second generation’ amine fungicide fenpropimorph, this class of compounds has already virtuall
机译:摘要尽管许多工人付出了相当大的努力,但自芬丙吗啉以来,胺类杀菌剂领域仍缺乏进展。到目前为止,各种不同胺类化合物的随机合成,以及铅结构芬丙吗啉的智能结构修饰(仅在巴斯夫就筛选了超过15000种胺),尚未产生新的市场产品。进一步的工作集中在已报道的芬丙吗啉的作用方式上,特别是抑制甾醇Δ14-还原酶。尽管对芬丙吗啉表现为甾醇模拟物的假设存在一些疑问,但“高能中间体”抑制剂的概念已被成功应用。氮杂甾醇模拟物的合理药物设计导致了许多非常有效的甾醇Δ14还原酶抑制剂,这些抑制剂在温室中也显示出很高的杀真菌活性。尽管这些化合物中有许多是比芬丙吗啉更强大的还原酶抑制剂,但在田间条件下,没有一种化合物显示出比这种已建立的杀菌剂更显着的优势。最有可能的是,芬丙吗啉已经表现出最大的杀真菌活性,这可以通过阻断甾醇 Δ14-还原酶来实现。这意味着,随着“第二代”胺类杀菌剂芬丙吗啉的发展,这类化合物已经几乎

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