Adventures in Scaffold Morphing: Discovery of Fused Ring Heterocyclic Checkpoint Kinase 1 (CHK1) Inhibitors was written by Yang, Bin;Vasbinder, Melissa M.;Hird, Alexander W.;Su, Qibin;Wang, Haixia;Yu, Yan;Toader, Dorin;Lyne, Paul D.;Read, Jon A.;Breed, Jason;Ioannidis, Stephanos;Deng, Chun;Grondine, Michael;De Grace, Nancy;Whitston, David;Brassil, Patrick;Janetka, James W.. And the article was included in Journal of Medicinal Chemistry in 2018.Quality Control of Benzyl 3-hydroxypiperidine-1-carboxylate This article mentions the following:
Checkpoint kinase 1 (CHK1) inhibitors are potential cancer therapeutics that can be utilized for enhancing the efficacy of DNA damaging agents. Multiple small mol. CHK1 inhibitors from different chem. scaffolds have been developed and evaluated in clin. trials in combination with chemotherapeutics and radiation treatment. Scaffold morphing of thiophene carboxamide ureas (TCUs), such as AZD7762 (1) and a related series of triazoloquinolines (TZQs), led to the identification of fused-ring bicyclic CHK1 inhibitors, 7-carboxamide thienopyridines (7-CTPs), and 7-carboxamide indoles. X-ray crystal structures reveal a key intramol. noncovalent sulfur-oxygen interaction in aligning the hinge-binding carboxamide group to the thienopyridine core in a coplanar fashion. An intramol. hydrogen bond to an indole NH was also effective in locking the carboxamide in the preferred bound conformation to CHK1. Optimization on the 7-CTP series resulted in the identification of lead compound 44, which displayed respectable drug-like properties and good in vitro and in vivo potency. In the experiment, the researchers used many compounds, for example, Benzyl 3-hydroxypiperidine-1-carboxylate (cas: 95798-22-4Quality Control of Benzyl 3-hydroxypiperidine-1-carboxylate).
Benzyl 3-hydroxypiperidine-1-carboxylate (cas: 95798-22-4) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.Quality Control of Benzyl 3-hydroxypiperidine-1-carboxylate
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem