Health and Crop Sciences Research Laboratory, Sumitomo Chemical Co., Ltd., Takarazuka, Japan.
Health and Crop Sciences Research Laboratory, Sumitomo Chemical Co., Ltd., Takarazuka, Japan.
Bioorg Med Chem. 2023 Jun 6;88-89:117332. doi: 10.1016/j.bmc.2023.117332. Epub 2023 May 16.
Pyridachlometyl is a unique pyridazine fungicide with a novel mode of action. Herein, we describe the pathway for the invention of pyridachlometyl. First, we identified a diphenyl-imidazo[1,2-a]pyrimidine as our proprietary lead with potent fungicidal activity. Then, aiming to simplify the chemical structure, we applied judicious estimations to explore monocyclic heterocycles as pharmacophores. This enabled the identification of a novel class of tetrasubstituted pyridazine compounds with potent fungicidal activity, likely retaining the same mode of action as the aforementioned compounds. The findings indicated bioisosteric similarity between diphenyl-imidazo[1,2-a]pyrimidine and pyridazine. Further structure-activity and mammalian safety investigations of pyridazine compounds resulted in the discovery of pyridachlometyl as a candidate for commercial development.
吡唑并[1,5-a]嘧啶是一种独特的嘧啶类杀菌剂，具有新颖的作用模式。本文描述了吡唑并[1,5-a]嘧啶发明的途径。首先，我们确定了二苯基-咪唑并[1,2-a]嘧啶作为具有强大杀菌活性的专利先导化合物。然后，为了简化化学结构，我们运用明智的估算来探索单环杂环作为药效团。这使得能够鉴定出一类具有强大杀菌活性的新型四取代嘧啶类化合物，它们可能保留与上述化合物相同的作用模式。研究结果表明二苯基-咪唑并[1,2-a]嘧啶和嘧啶之间具有生物等排相似性。进一步对嘧啶类化合物的结构-活性和哺乳动物安全性进行研究，发现吡唑并[1,5-a]嘧啶是一种有商业开发前景的候选药物。
