5-(4-Chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)isoxazole: A potent, selective antagonist at human cloned dopamine D4 receptors

Journal of Medicinal Chemistry

Volumn 39, Issue 10, 1996, Pages 1943-1945

  Rowley, Michael ^a   Broughton, Howard B ^a   Collins, Ian ^a   Baker, Raymond ^a   Emms, Frances ^a   Marwood, Rosemarie ^a   Patel, Shil ^a   Patel, Smita ^a   Ragan, C Ian ^a   Freedman, Stephen B ^a   Leeson, Paul D ^a  

^a NEUROSCIENCE RESEARCH CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 QUINUCLIDINOL; 5 (4 CHLOROPHENYL) 4 METHYL 3 [1 (2 PHENYLETHYL) 4 PIPERIDINYL]ISOXAZOLE; BENZALDEHYDE DERIVATIVE; CLOZAPINE; DOPAMINE 4 RECEPTOR; DOPAMINE RECEPTOR BLOCKING AGENT; HALOPERIDOL; ISOXAZOLE DERIVATIVE; L 741742; PYRAZOLE DERIVATIVE; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG;

AGRANULOCYTOSIS; ANIMAL CELL; ARTICLE; CHO CELL; CONTROLLED STUDY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; EXTRAPYRAMIDAL SYMPTOM; HUMAN; HUMAN CELL; NEGATIVE SYNDROME; NONHUMAN; RECEPTOR AFFINITY; SCHIZOPHRENIA;

CLONING, MOLECULAR; DOPAMINE ANTAGONISTS; HUMANS; ISOXAZOLES; PIPERIDINES; RECEPTORS, DOPAMINE D2; RECEPTORS, DOPAMINE D4;

EID: 15844385079     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960072u     Document Type: Article

References (18)

1. Snyder, S. H. Dopamine receptors, neuroleptics, and schizophrenia. Am. J. Psychiatry 1981, 138, 461-464.
2. Baldessarini, R. J.; Tarsey, D. Dopamine and the pathophysiology of dyskinesias induced by antipsychotic drugs. Annu. Rev. Neurosci. 1980, 3, 23.
3. Ben-Johnathon, N. Dopamine: A prolactin inhibiting hormone. Endocr. Rev. 1985, 6, 564.
4. Fitton, A.; Heel, R. C. Clozapine. A review of its pharmacological properties, and therapeutic use in schizophrenia. Drugs 1990, 40, 722-747.
5. Schwartz, J. T.; Brotman, A. W. A Clinical Guide to Antipsychotic Drugs. Drugs 1992, 44, 981-992.
6. Dearry, J. R.; Gingrich, J. A.; Falardeau, R. T.; Fremeau, R. T.; Bates, M. D.; Caron, M. Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature 1990, 347, 72-76.
7. 2 dopamine receptor. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 9762-9766.
8. 3) as a target of neuroleptics. Nature 1990, 347, 72-76.
9. 4 receptor with high affinity for the antipsychotic clozapine. Nature 1991, 350, 610-614.
10. 1. Nature 1991, 350, 614-619.
11. (a) Seeman, P.; Guan, H.-C.; Van Tol, H. H. M. Dopamine D4 receptors elevated in schizophrenia. Nature 1993, 365, 441-445.
12. (b) Murray, A. M.; Hyde, T. M.; Knable, M. B.; Herman, M. M.; Bigelow, L. B.; Carter, J. M.; Weinberger, D. R.; Kleinman, J. E. Distribution of putative D4 dopamine receptors in postmortem striatum from patients with schizophrenia. J. Neurosci. 1995, 15, 2186-2191.
13. 3H]raclopride binding in postmortem caudate nucleus of subjects with schizophrenia or major depression. Brain Res. 1995, 687, 109-116.
14. Freedman, S. B.; Patel, S.; Marwood, R.; Emms, F.; Seabrook, G. R.; Knowles, M. R.; McAllister, G. Expression and pharmacological characterisation of the human D3 dopamine receptor. J. Pharmacol. Exp. Ther. 1994, 268, 417-426.
15. McAllister, G.; Knowles, M. R.; Ward-Booth, S. M.; Sinclair, H. A.; Patel, S.; Marwood, R.; Emms, F.; Patel, S.; Smith, G. R.; Seabrook, G. R.; Freedman, S. B. Functional coupling of human D2, D3, and D4 dopamine receptors in HEK293 cells. J. Recep. Sig. Trans. Res. 1995, 15, 267-281.
16. Carhart, R.; Smith, D. H.; Venkataraghavan, R. J. Chem. Inf. Comput. Sci. 1985, 25, 64-73.
17. Sheridan, R.; Kearsley, S. K. Molecular Systems Department, MRL, Rahway, NJ.
18. Yanina, A. D.; Trubitsyna, T. K.; Mikhlina, E. E.; Yakhontov, L. N. Synthesis and pharmalogical properties of 2- and 2,3-substituted quinuclidines. Khim. Farm. Zh. 1987, 21, 808-811.