214834-18-1Relevant articles and documents
Discovery of Novel Piperidinylthiazole Derivatives As Broad-Spectrum Fungicidal Candidates
Wu, Qifan,Zhao, Bin,Fan, Zhijin,Guo, Xiaofeng,Yang, Dongyan,Zhang, Nailou,Yu, Bin,Zhou, Shuang,Zhao, Jiabao,Chen, Fan
, p. 1360 - 1370 (2019)
Oxathiapiprolin is one of the best active fungicides discovered for oomycetes control. To develop a fungicide candidate with a broad spectrum of activity, 22 new piperidinylthiazole derivatives were designed and synthesized. Compound 5l showed the best activity against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo with 100% and 80% of inhibition, respectively, at 1 mg/L, and 72.87% of field efficacy against P. cubensis at 1 g ai/667 m2 validated these results. Compound 5i exhibited a broad spectrum of excellent activity against Sclerotinia sclerotiorum with EC50 = 0.30 mg/L (>10 times more active than oxathiapiprolin and azoxystrobin in vitro), good activity against Botrytis cinerea, Cercospora arachidicola, and Gibberella zeae with EC50 of 14.54, 5.57, and 14.03 mg/L in vitro and against P. cubensis and P. infestans with 60% and 30% inhibition rates, respectively, at 1 mg/L in vivo. Mode of action studies by RNA sequencing analysis discovered oxysterol-binding protein (OSBP), chitin synthase (CHS1), and (1,3)-β-glucan synthase (FKS2) as the potent target of 5i against S. sclerotiorum. Quenching studies validated that OSBP was the same target of both 5i and oxathiapiprolin; it was quenched by both of them. Our studies discovered isothiazole-containing piperidinylthiazole as an OSBP target-based novel lead for fungicide development.
Design and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists
Zuo, Zeping,Chen, Miaomiao,Shao, Xiaoni,Qian, Xinying,Liu, Xiaocong,Zhou, Xia,Xiang, Jiawei,Deng, Pengchi,Li, Yan,Jie, Hui,Liu, Chunqi,Cen, Xiaobo,Xie, Yongmei,Zhao, Yinglan
, (2020/01/08)
A series of novel tetrahydropyridine derivatives were prepared and evaluated using cell-based measurements. Systematic optimization of general structure G-1 led to the identification of compound 35 (EC50 = 4.9 nM) and 37 (EC50 = 8.8 nM) with high GPR119 agonism activity and moderate clog P. Through single and long-term pharmacodynamic experiments, we found that compound 35 showed a hypoglycemic effect and may have an effect on improving basal metabolic rate in DIO mice. Both in vitro and in vivo tests indicated that compound 35 was a potential potent GPR119 agonist in allusion to T2DM treatment.
Synthetic method and application of piperidyl thiazole formamide compound
-
, (2020/06/09)
The invention relates to a 2-(4-piperidyl)-thiazole-4-formamide compound and a synthetic method and medicinal evaluation thereof. The synthetic method comprises the following steps: carrying out a substitution reaction between N-Boc-4-piperidine-carboxylic acid and ammonium chloride to prepare an intermediate 2; carrying out a thiolation reaction between the compound 2 and a Lawesson reagent to obtain an intermediate 3; carrying out a reaction between the compound 3 and ethyl bromopyruvate to obtain an intermediate 4; carrying out esterolysis on the compound 4 to obtain a compound 5; carryingout a reaction between the compound 5 and ammonia to obtain an intermediate 6; deprotecting the Boc protected compound 6 to obtain a compound 7; performing acid condensation on the compound 7 to obtain an intermediate 8; deprotecting the Boc protected intermediate 8 to obtain a compound 9; and carrying out a reaction between the compound 9 and different isocyanates to obtain a final product. An MTT method is adopted for tests, and it shows that part of the 2-(4-piperidyl)-thiazole-4-formamide compounds have certain anti-tumor activity, wherein the antitumor activity of a compound 10f-10m is superior to that of a compound 10a-10d.
