N-(substituted-phenyl) piperazines: Antagonists with high binding and functional selectivity for dopamine D4 receptors

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 11, 1996, Pages 1227-1232

  Boyfield, Izzy ^a   Coldwell, Martyn C ^a   Hadley, Michael S ^a   Healy, Maureen A M ^a   Johns, Amanda ^a   Nash, David J ^a   Riley, Graham J ^a   Scott, Emma E ^a   Smith, Stephen A ^a   Stemp, Geoffrey ^a   Wilson, Karl ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DOPAMINE 2 RECEPTOR; DOPAMINE 4 RECEPTOR; DOPAMINE RECEPTOR BLOCKING AGENT; PIPERAZINE DERIVATIVE;

ARTICLE; BINDING AFFINITY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; EXTRAPYRAMIDAL SYMPTOM; RECEPTOR AFFINITY; SCHIZOPHRENIA;

EID: 0029895070     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00198-9     Document Type: Article

References (15)

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10. 4 selectivity is NGD 94-1, but no structure has been revealed - Tallman, J.F. American College of Neuropsychopharmacology 33rd Annual Meeting, San Juan, Puerto Rico, December 12-16, 1994.
11. 2 (long) receptors expressed in CHO cells were obtained from the Garvan Institute (Melbourne). The quoted figures are the means of at least two determinations at each receptor.
12. All compounds of Tables 1 - 4 gave satisfactory spectroscopic/analytical data. See also reference 15.
13. 3 receptors.
14. 2, before changing to medium without FCS. After a further 16-18h, cups were loaded into the sensor chambers of the microphysiometer and the chambers perfused with running medium (bicarbonate-free Dulbecco's modified Eagles medium containing 2 mM glutamine and 44 mM NaCl). For agonist experiments, cells were exposed to increasing concentrations of agonist at half hour intervals. For antagonist experiments, cells were exposed five times (at half hour intervals) to a single concentration of quinpirole (30 nM) before addition of the first antagonist concentration. After a 30 min interval, cells were again stimulated with quinpirole (in the continued presence of the antagonist), before the second (higher) antagonist concentration was applied. In all, responses in the presence of five increasing concentrations of antagonist were determined. Peak acidification rate to each agonist concentration was determined and concentration-response curves fitted using RoboFit (Tilford N.S.; Bowen, W.P.; Baxter, G.S. RoboFit: A Versatile Macro-Driven Template for Curve Fitting, Analysis and Presentation in Microsoft Excel. Br. J. Pharmacol. 1995, 115, 160P).
15. 3O. 2HCl requires C, 53.7; H, 7.6; N, 9.9%. Melting Point: 162-164°C.