On October 15, 2015, Kusumi, Kensuke; Shinozaki, Koji; Yamaura, Yoshiyuki; Hashimoto, Ai; Kurata, Haruto; Naganawa, Atsushi; Ueda, Hideyuki; Otsuki, Kazuhiro; Matsushita, Takeshi; Sekiguchi, Tetsuya; Kakuuchi, Akito; Seko, Takuya published an article.Safety of 4-(4-Chlorophenyl)piperidin-4-ol The title of the article was Discovery of novel S1P2 antagonists. Part 2: Improving the profile of a series of 1,3-bis(aryloxy)benzene derivatives. And the article contained the following:
The initial lead compound was modified to improve its metabolic stability. The resulting compound showed excellent metabolic stability in rat and human liver microsomes. The authors subsequently designed and synthesized compound N-[3-[4-(aminocarbonyl)phenoxy]-5-(4-fluorophenoxy)phenyl]-4-(4-chlorophenyl)-4-hydroxy-1-piperidinecarboxamide (I), which showed improved S1P2 antagonist activity and good metabolic stability. The subsequent introduction of a carboxylic acid moiety into I resulted in 4-[3-(4-fluorophenoxy)-5-[[[4-(4-fluorophenyl)-4-hydroxy-1-piperidinyl]carbonyl]amino]phenoxy]benzoic acid (II), which showed potent antagonist activity towards S1P2 with a much smaller species difference between human S1P2 and rat S1P2. Compound II also showed good metabolic stability and an improved safety profile compared with compound I. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Safety of 4-(4-Chlorophenyl)piperidin-4-ol
The Article related to aryloxybenzene preparation pharmacokinetics, antagonist, g protein-coupled receptors, metabolic stability, sphingosine-1-phosphate receptor 2, Pharmacology: Structure-Activity and other aspects.Safety of 4-(4-Chlorophenyl)piperidin-4-ol
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem