Synthesis and antidepressant activity of optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl) propan-1-ol (SIPI5056)

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 3, 2010, Pages 1256-1259

  Weng, Zhijie ^a   Li, Jianqi ^a  

^a SHANGHAI INSTITUTE OF PHARMACEUTICAL INDUSTRY   (China)

Author keywords

Antidepressant; Optical isomer; Triple reuptake inhibitor

Indexed keywords

2 (4 BENZYLPIPERAZIN 1 YL) 1 (5 CHLORO 6 METHOXYNAPHTHALEN 2 YL) PROPAN 1 OL; ALANINE; ANTIDEPRESSANT AGENT; UNCLASSIFIED DRUG; NAPHTHALENE DERIVATIVE; PIPERAZINE DERIVATIVE; PROPANOL;

ARTICLE; CHIRALITY; DRUG ACTIVITY; DRUG SYNTHESIS; ISOMER; STRUCTURE ACTIVITY RELATION; ANIMAL; BRAIN CORTEX; COMPARATIVE STUDY; DRUG EFFECTS; LD 50; METABOLISM; MOUSE; RAT; STEREOISOMERISM; SYNAPTOSOME; SYNTHESIS; TOXICITY;

ANIMALS; ANTIDEPRESSIVE AGENTS; CEREBRAL CORTEX; LETHAL DOSE 50; MICE; NAPHTHALENES; PIPERAZINES; PROPANOLS; RATS; STEREOISOMERISM; SYNAPTOSOMES;

EID: 74049145340     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.11.108     Document Type: Article

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15. 2O: C, 56.24; H, 6.51; N, 5.25. Found: C, 56.04; H, 6.36; N, 5.30.
16. 2O: C, 56.24; H, 6.51; N, 5.25. Found: C, 56.44; H, 6.21; N, 5.30.
17. 2O: C, 56.24; H, 6.51; N, 5.25. Found: C, 56.37; H, 6.38; N, 5.24.
18. 2O: C, 56.24; H, 6.51; N, 5.25. Found: C, 56.15; H, 6.28; N, 5.26.
19. +).
20. Preparation of synaptosomes: Rats were decapitated, the brains rapidly excised, and frontal cortex dissected out on ice-cold saline (4 °C). The 3 g tissue was homogenized in 30 ml of ice-cold 0.32 M sucrose and then centrifuged (1500g) for 10 min (4 °C). The pellet was discarded and the supernatant centrifuged (20,000g) for 30 min (4 °C). After refined, the pellet was resuspended in buffer and immediately used. Protein content was determined with kit of total protein.
21. Reuptake of monoamine transmitters: According to the method described by literatures (Br. J. Pharmacol. 1997, 122, 302 and 1992, 105, 147), in the tubes, 1.0 ml artificial cerebral fluid (adding oxygen in advance), 20 μl suspension of synaptosomes and 10 μl solution of compound were added (all done at 4 °C). After mixing, the tubes were incubated 5 min in 37 °C. Uptake was started by addition of 10 μl [3H]-5-HT, [3H]-NA or [3H]-DA (300 nM), after another mixing, the tubes were incubated again 5 min in 37 °C. The reaction was stopped by cooling the tubes in ice; the samples were then filtered through glass fiber filters and washed twice with artificial cerebral fluid. After drying in 60-70 °C, the filter membranes were put into scintillation tubes. Filter-bound radioactivity was counted by scintillation spectrometry. The difference in [3H]-5-HT, [3H]-NA or [3H]-DA at 37 °C and 0 °C was taken as a measure of active uptake.