Design and synthesis of Grp94 selective inhibitors based on Phe199 induced fit mechanism and their anti-inflammatory effects was written by Xu, Shicheng;Guo, Anping;Chen, Nan-nan;Dai, Wei;Yang, Huan-aoyu;Xie, Wenqin;Wang, Mengjie;You, Qi-Dong;Xu, Xiao-Li. And the article was included in European Journal of Medicinal Chemistry in 2021.Category: piperidines This article mentions the following:
Glucose-regulated protein 94 (Grp94), a member of the Heat shock protein 90 (Hsp90) family, is implicated in many human diseases, including cancer, neurodegeneration, inflammatory, and infectious diseases. Here, we describe our effort to design and develop a new series of Grp94 inhibitors based on Phe199 induced fit mechanism. Using an alkynyl-containing inhibitor as a starting point, we developed compound 4 (I), which showed potent inhibitory activity toward Grp94 in a fluorescence polarization-based assay. With improved physicochem. properties and suitable pharmacokinetic properties, compound 4 was advanced into in vivo bioactivity evaluation. In a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC), compound 4 showed anti-inflammatory property and reduced the levels of pro-inflammatory cytokines (TNF-伪 and IL-6). Together, these findings provide evidence that this approach may be promising for further Grp94 drug development efforts. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Category: piperidines).
1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Category: piperidines
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem