1207438-75-2Relevant academic research and scientific papers
Preparation of (S)-4-(1-(3,4-dichlorophenyl)-2-methoxyethyl)piperidine
Yamashita, Masayuki,Taya, Naohiro,Nishitani, Mitsuyoshi,Oda, Katsuaki,Kawamoto, Tetsuji,Kimura, Eiji,Ishichi, Yuji,Terauchi, Jun,Yamano, Toru
, p. 935 - 942 (2015)
Abstract The novel triple reuptake inhibitor (S)-4-(1-(3,4-dichlorophenyl)-2-methoxyethyl)piperidine monohydrochloride 1 possesses a unique 2-phenyl-2-(piperidin-4-yl)ethanol moiety with a stereogenic center at the benzyl position. To synthesize 1 as the (S)-isomer, three possible routes were investigated; (1) the lipase-catalyzed kinetic resolution of tert-butyl 4-(1-(3,4-dichlorophenyl)-2-hydroxyethyl)piperidine-1-carboxylate 2 utilizing PS-IM from Pseudomonas sp. as the lipase; (2) the asymmetric hydrogenation of tert-butyl 4-(1-(3,4-dichlorophenyl)-2-oxoethyl)piperidine-1-carboxylate 5 utilizing dynamic kinetic resolution; and (3) the resolution of racemic [1-(tert-butoxycarbonyl)piperidin-4-yl](3,4-dichlorophenyl)acetic acid 8 with (S)-phenylethylamine. The design of the asymmetric reaction using retrosynthesis, as well as the extensive exploration of enzymes, asymmetric hydrogenation catalysts, and resolving reagents, were all important to afford the optically active compound 1 in excellent yield.
Novel triple reuptake inhibitors with low risk of CAD associated liabilities: Design, synthesis and biological activities of 4-[(1S)-1-(3,4- dichlorophenyl)-2-methoxyethyl]piperidine and related compounds
Ishichi, Yuji,Kimura, Eiji,Honda, Eiji,Yoshikawa, Masato,Nakahata, Takashi,Terao, Yasuko,Suzuki, Atsuko,Kawai, Takayuki,Arakawa, Yuuichi,Ohta, Hiroyuki,Kanzaki, Naoyuki,Nakagawa, Hideyuki,Terauchi, Jun
, p. 4600 - 4613 (2013/07/26)
A novel triple reuptake inhibitor with low potential of liabilities associated with cationic amphiphilic drug (CAD) was identified following an analysis of existing drugs. Low molecular weight (MW a series of piperidine compounds was designed with consideration of the common characteristic features of CNS drugs. Optimization of the side chain by adjusting overall lipophilicity suggested that incorporation of a methoxymethyl group could provide compounds with a balance of both potent reuptake inhibition and low liability potential. Compound (S)-3a showed a potent antidepressant-like effect in the mice tail suspension test (MED = 10 mg/kg, p.o.), proportional monoamine transporter occupancies and enhancement of monoamine concentrations in mouse prefrontal cortex.
