Synthesis and dopamine transporter affinity of chiral 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(2-hydroxypropyl)piperazines as potential cocaine abuse therapeutic agents

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 3, 2003, Pages 553-556

  Hsin, Ling Wei ^a,c   Prisinzano, Thomas ^a   Wilkerson, Chavon R ^a   Dersch, Christina M ^b   Horel, Robert ^b   Jacobson, Arthur E ^a   Rothman, Richard B ^b   Rice, Kenner C ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b NIDA Addiction Research Center   (United States)

^c NATIONAL TAIWAN UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 (BENZHYDRYLOXY)ETHYL] 4 (3 PHENYLPROPYL)PIPERAZINE; 1 [2 (BISPHENYLMETHOXY)ETHYL]PIPERAZINE; 1 [2 [BIS(4 FLUOROPHENYL)METHOXY]ETHYL]PIPERAZINE; DOPAMINE TRANSPORTER; LIGAND; PIPERAZINE DERIVATIVE; SEROTONIN TRANSPORTER; UNCLASSIFIED DRUG; VANOXERINE;

ALKYLATION; ARTICLE; CHIRALITY; COCAINE DEPENDENCE; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENANTIOMER; ENANTIOSELECTIVITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; COCAINE; COCAINE-RELATED DISORDERS; CONDITIONING, OPERANT; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; DOPAMINE UPTAKE INHIBITORS; LIGANDS; MACACA MULATTA; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; NERVE TISSUE PROTEINS; PIPERAZINES; PROTEIN BINDING; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037328363     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00940-X     Document Type: Article

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17. 1H NMR, mass spectral data were obtained for all final products. Elemental analyses were within ±0.4% for C, H, and N.
18. 2) to afford (R)-9 as a pale-yellow oil. The oil was dissolved in MeOH and maleic acid (2.2 equiv) was added. The precipitate was collected by filtration, recrystallized from MeOH to give 0.4 g (60%) of (R)-9-dimaleate as a white crystalline solid.
19. Uncorrected melting points: 8a: 182-184°C; 8b: 183-185°C; 8c: 180-182°C; (S)-(+)-9: 167-168°C; (R)-(-)-9: 169-170°C; (S)-(+)-10: 163-164°C; (R)-(-)-10: 164-165°C; (±)-11: 182-183°C; (S)-(+)-11: 181-182°C; (R)-(-)-11: 182-183°C; (1S,2R)-(+)-12: 169-170°C; (1R,2S)-(-)-12: 168-169°C.
20. The enantiomers were separated by HPLC using a semi-preparative chiral column (Daicel chiralcel OD, 2 cm × 25 cm); UV detection at 254 nm; flow rate 6 mL/min; 2% 2-propanol in n-hexane in the presence of 0.2% diethylamine.
21. 20 =-12.6°.