Safety of tert-Butyl 4-hydroxypiperidine-1-carboxylateIn 2021 ,《Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl Moiety》 was published in Journal of Medicinal Chemistry. The article was written by Ikeda, Shuhei; Sugiyama, Hideyuki; Tokuhara, Hidekazu; Murakami, Masataka; Nakamura, Minoru; Oguro, Yuya; Aida, Jumpei; Morishita, Nao; Sogabe, Satoshi; Dougan, Douglas R.; Gay, Sean C.; Qin, Ling; Arimura, Naoto; Takahashi, Yasuko; Sasaki, Masako; Kamada, Yusuke; Aoyama, Kazunobu; Kimoto, Kouya; Kamata, Makoto. The article contains the following contents:
The therapeutic potential of monoacylglycerol lipase (MAGL) inhibitors in central nervous system-related diseases has attracted attention worldwide. However, the availability of reversible-type inhibitor is still limited to clarify the pharmacol. effect. Herein, we report the discovery of novel spiro chem. series as potent and reversible MAGL inhibitors with a different binding mode to MAGL using Arg57 and His121. Starting from hit compound 1 and its co-crystal structure with MAGL, structure-based drug discovery (SBDD) approach enabled us to generate various spiro scaffolds like 2a (azetidine-lactam), 2b (cyclobutane-lactam), and 2d (cyclobutane-carbamate) as novel bioisosteres of 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl moiety in 1 with higher lipophilic ligand efficiency (LLE). Optimization of the left hand side afforded 4f (I) as a promising reversible MAGL inhibitor, which showed potent in vitro MAGL inhibitory activity (IC50 6.2 nM), good oral absorption, blood-brain barrier penetration, and significant pharmacodynamic changes (2-arachidonoylglycerol increase and arachidonic acid decrease) at 0.3-10 mg/kg, po. in mice. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Safety of tert-Butyl 4-hydroxypiperidine-1-carboxylate)
tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas:109384-19-2) is a 4-hydroxypyridine with a boc protecting group used in the preparation of neurologically active agents and other pharmaceutical compounds.Safety of tert-Butyl 4-hydroxypiperidine-1-carboxylate
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem