Discovery of selective dopamine D4 receptor antagonists: 1-aryloxy-3-(4-aryloxypiperidinyl)-2-propanols

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 11, 1997, Pages 1377-1380

  Wright, Jon L ^a   Gregory, Tracy F ^a   Heffher, Thomas G ^a   MacKenzie, Robert G ^a   Pugsley, Thomas A ^a   Vander Meulen, Seth ^a   Wise, Lawrence D ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 PIPERIDINYL 2 PROPANOL DERIVATIVE; DOPAMINE 4 RECEPTOR; DOPAMINE RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; DOPAMINE METABOLISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SYNTHESIS; ENANTIOMER; INTRAPERITONEAL DRUG ADMINISTRATION; NONHUMAN; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

EID: 0030986037     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00233-3     Document Type: Article

References (10)

1. Meltzer, H. Y.; Stahl, S. M. Schizophr. Bull. 1976, 2, 19.
2. Baldessarini, R. J.; Tarsy, D. Annu. Rev. Neurosci. 1980, 3, 23.
3. Van Tol, H. H. M.; Bunzow, J. R.; Guan, H. -C.; Sunahara, R. K.; Seeman, P.; Niznik, H. B.; Civelli, O. Nature (London), 1991, 350, 610.
4. Matsumoto, M.; Hidaka, K.; Tada, S.; Tasaki, Y.; Yamaguchi, T. Mol. Brain Res. 1995, 29, 157.
5. 3H]spiperone as previously described: Wright, J. L.; Caprathe, B. W.; Downing, D. M.; Glase, S. A.; Heffner, T. G.; Jaen, J. C.; Johnson, S. J.; Kesten, S. R.; MacKenzie, R. G.; Meltzer, L. T.; Pugsley, T. A.; Smith, S. J.; Wise, L. D.; Wustrow, D. J. J. Med. Chem. 1994, 37, 3523.
6. 1H NMR, IR, MS and microanalysis.
7. Chiral HPLC analyses were performed on a 4.6 × 250 mm Daicel Chiralpak AD column eluting with 20% isopropanol/hexane (both containing 0.1% diethylamine) at 1.0 mL/min. Typical retention times were 8.7 min for 17 and 11.3 min for 18.
8. (a) Lajiness, M. E.; Chio, C. L.; Huff, R. M. J. Pharmacol. Exp. Ther. 1993, 267, 1573.
9. (b) Chio, C. L.; Lajiness, M. E.; Huff, R. M. Mol. Pharm. 1994, 45, 51.
10. DOPA accumulation in rat brain after administration of compounds was used as a measure of effects on DA synthesis. This test was carried out according to methods described previously: Pugsley, T. A.; Davis, M. D.; Akunne, H. C.; MacKenzie, R. G.; Shih, Y. H.; Damsma, G.; Wikstrom, H.; Whetzel, S. Z.; Georgic, L. M.; Cooke, L. W.; DeMattos, S. B.; Corbin, A. E.; Glase, S. A.; Wise, L. D.; Dijkstra, D.; Heffner, T. G. J. Pharm. Exp. Ther. 1995, 275(3), 1355.