BACKGROUNDAs an investigative program around the development of novel oomycetes fungicides, a systematic exploration of piperidinyl thiazole fungicides employing a bioisosteric replacement strategy was planned.RESULTSA series of novel piperidinyl thiazole analogues were designed, synthesised, and evaluated as fungicides in vitro and in vivo against three oomycete fungal pathogens: Phytophthora infestans (P. infestans), Plasmopara viticola (P. viticola), and Pseudoperonospora cubensis (P. cubensis). Variation at four different regions of piperidinyl thiazole fungicides like Oxathiapiprolin and Fluoxapiprolin was considered. All variations delivered excellent in vitro and in vivo activity against P. infestans at extremely low concentrations. O‐linked heterocyles, bicyclic piperidines, and sulfoximine‐substituted aryls demonstrated the most robust transfer of in vitro activity into the greenhouse, while pyridones, acylated sulfoximines, and sultams showed less consistent results concerning the transfer. Specific compounds were selected for deeper evaluation of oomycetes activity. Several of them with representatives of all the series showed an excellent in vivo activity against P. viticola and P. cubensis. Among the most active compounds, P14 and P25 were further profiled in advanced studies and were found to have a robust curative potential. P14, P15, and P25 provided excellent control of P. infestans (in potato), P. viticola (in grapes), and P. cubensis (in cucumber) in field trials at dose rates of 20 and 30 g per hectare.CONCLUSIONSA bioisosteric replacement strategy was successfully employed to identify novel piperidine thiazole derivatives with robust and commercially interesting control of oomycetes diseases in the greenhouse and under field conditions. A systematic exploration of various modifications of the piperidine thiazole class and their structure activity relationships was described. © 2024 Society of Chemical Industry.

中文翻译：

---

新型哌啶基噻唑衍生物的合成及其抗真菌活性


背景作为围绕新型卵菌类杀菌剂开发的一项研究计划，计划对采用生物等排替代策略的哌啶基噻唑类杀菌剂进行系统探索。 结果设计、合成了一系列新型哌啶基噻唑类似物，并针对三种杀菌剂进行了体外和体内评价。卵菌真菌病原体：致病疫霉（P. infestans）、葡萄生单轴霉（P. viticola）和古巴假霜霉（P.cubensis）。考虑了哌啶基噻唑类杀菌剂（例如 Oxathiapiprolin 和 Fluoxapiprolin）在四个不同区域的变化。所有变体均在极低浓度下提供了优异的针对致病疫霉的体外和体内活性。 O-连接杂环、双环哌啶和亚磺酰亚胺取代的芳基证明了将体外活性最有力地转移到温室中，而吡啶酮、酰化亚磺酰亚胺和磺内酰胺在转移方面表现出不太一致的结果。选择特定化合物来更深入地评估卵菌活性。其中一些以及所有系列的代表均表现出针对 P. viticola 和 P.cubensis 的优异体内活性。在最活跃的化合物中，P14 和 P25 在高级研究中得到了进一步分析，并被发现具有强大的治疗潜力。在田间试验中，P14、P15 和 P25 以每公顷 20 和 30 g 的剂量对马铃薯疫病菌（马铃薯）、葡萄疫病菌（葡萄）和黄瓜疫病菌（黄瓜）提供了良好的防治效果。结论生物电子等排替代策略已成功用于鉴定新型哌啶噻唑衍生物，对温室和田间条件下的卵菌疾病具有强大且具有商业意义的控制作用。 描述了哌啶噻唑类的各种修饰及其结构活性关系的系统探索。 © 2024 化学工业协会。