194017-70-4Relevant articles and documents
Discovery of Novel Cytochrome bc1 Complex Inhibitor Based on Natural Product Neopeltolide
Chen, Qiong,Chen, Tao,Gao, Meng-Qi,Wang, Yu-Xia,Yang, Guang-Fu,Zhang, Rui,Zhu, Xiao-Lei
, p. 263 - 268 (2022/05/12)
Background: Natural products (NPs) are important sources for the design of new drugs and agrochemicals. Neopeltolide, a marine NP, has been identified as a potent Qo-site inhibitor of cytochrome bc1 complex. Methods: In this study, a series of neopeltolide derivatives was designed and synthesized by the simplification of its 14-membered macrolactone ring with a diphenyl ether fragment. The enzymatic inhibition bioassays and mycelium growth inhibition experiments against a range of fungi were performed to determine their fungicidal activities. Results: The derivatives have potent activity against the porcine bc1 complex. Compound 8q showed the best activity with an IC50 value of 24.41 nM, which was 8-fold more effective than that of positive control azoxystrobin. Compound 8a exhibited a 100% inhibitory rate against Zymoseptoria tritici and Alternaria solani at a 20 mg/L dose. Conclusion: Computational results indicated that compounds with suitable physicochemical properties, as well as those forming a hydrogen bond with His161, would have good fungicidal activity. These data could be useful for the design of bc1 complex inhibitors in the future.
Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators
Bridges, Thomas M.,Kennedy, J. Phillip,Hopkins, Corey R.,Conn, P. Jeffrey,Lindsley, Craig W.
scheme or table, p. 5617 - 5622 (2010/11/05)
This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M5-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan Gq mAChR M1, M3, M5 PAM. An iterative parallel synthesis approach was employed to incorporate basic heterocycles to improve physiochemical properties.
SUBSTITUTED CARBOXYLIC ACID DERIVATIVES
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Page/Page column 25, (2010/11/29)
The invention provides novel substituted carboxylic acid derivatives that bind to receptor as ligands of human peroxisome proliferator-activated receptor (PPAR) to activate it and exhibit potent triglyceride-lowering action, cholesterol-lowering action an