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 published their research in Bioorganic & Medicinal Chemistry on August 1 ,2013. The article was titled 《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》.Product Details of 658-98-0 The article contains the following contents:
A novel triple reuptake inhibitor with low potential of liabilities associated with cationic amphiphilic drug (CAD) was identified following an anal. of existing drugs. Low mol. weight (MW < ca. 300), low aromatic ring count (number = 1) and reduced lipophilicity (C log P < 3.5) were hypothesized to be key factors to avoid the CAD associated liabilities (CYP2D6 inhibition, hERG inhibition and phospholipidosis). Based on the hypothesis, 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)-I 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. In the experiment, the researchers used 3-Chloro-4-fluorophenylacetonitrile(cas: 658-98-0Product Details of 658-98-0)
3-Chloro-4-fluorophenylacetonitrile(cas: 658-98-0) belongs to nitriles. Nitriles are found in many useful compounds. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Product Details of 658-98-0 Industrially, the main methods for producing nitriles are ammoxidation and hydrocyanation. Both routes are green in the sense that they do not generate stoichiometric amounts of salts.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts