Interactive SAR studies: Rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists

Journal of Medicinal Chemistry

Volumn 45, Issue 21, 2002, Pages 4594-4597

  Bettinetti, Laura ^a   Schlotter, Karin ^a   Hübner, Harald ^a   Gmeiner, Peter ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE; BENZOTHIOPHENE 2 CARBOXAMIDE; BENZOTHIOPHENE DERIVATIVE; BP 897; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; DOPAMINE 3 RECEPTOR BLOCKING AGENT; DOPAMINE 3 RECEPTOR STIMULATING AGENT; DOPAMINE 4 RECEPTOR; METHOXYPHENYLPIPERAZINYLBUTYLAMIDE; PHENYL GROUP; PYRAZOLO[1,5 A]PYRIDINE; SEROTONIN 1A RECEPTOR; SEROTONIN 2 RECEPTOR; SPIPERONE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CYCLOADDITION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; LIGAND BINDING; NONHUMAN; REACTION ANALYSIS; RECEPTOR AFFINITY; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANIMALS; CHO CELLS; CRICETINAE; DOPAMINE AGONISTS; DOPAMINE ANTAGONISTS; HUMANS; LIGANDS; MITOSIS; PIPERAZINES; RADIOLIGAND ASSAY; RECEPTORS, DOPAMINE D2; RECEPTORS, DOPAMINE D3; STRUCTURE-ACTIVITY RELATIONSHIP; SWINE; THIOPHENES;

EID: 0037057547     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm025558r     Document Type: Article

References (26)

1. 3) as a target for neuroleptics. Nature 1990, 347, 146-151.
2. 3 dopamine receptors. Science 1993, 260, 1814-1816.
3. 3 receptor test in vitro predicts decreased cocaine self-administration in rats. Neuroreport 1997, 8, 2373-2377.
4. (c) Staley, J. K.; Mash, D. C. Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities. J. Neurosci. 1996, 16, 6100-6106.
5. 3 receptor agonist. Nature 1999, 400, 371-375.
6. 3 receptor antagonist with high oral bioavailability and CNS penetration in the rat. J. Med. Chem. 2000, 43, 1878-1885 and references therein.
7. 3 receptor antagonists. Bioorg. Med. Chem. Lett. 1998, 8, 2715-2718.
8. 3 dopamine receptor ligands. Bioorg. Med. Chem. Lett. 1997, 7, 2403-2408.
9. (a) Löber, S.; Hübner, H.; Utz, W.; Gmeiner, P. Rationally Based Efficacy Tuning of Selective Dopamine D4 Receptor Ligands Leading to the Complete Antagonist 2-[4-(4-Chlorophenyl)piperazin-1-ylmethyl] pyrazolo-[1,5-a]pyridine (FAUC 213). J. Med. Chem. 2001, 44 2691-2694.
10. (b) Lanig, H.; Utz, W.; Gmeiner, P. Comparative Molecular Field Analysis of Dopamine D4 Receptor Antagonists Including 3-[4-(4-Chlorophenyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 113), 3-[4-(4-Chlorophenyl)piperazin-1-ylmethyl]-1H-pyrrolo[2,3-b]pyridine (L-745,870), and Clozapine. J. Med. Chem. 2001, 44, 1151-1157.
11. Gösl, R.; Meuwsen, A. 1-Aminopyridinium iodide. Org. Synth. 1963, 43, 1-3.
12. Gmeiner, P.; Sommer, J. Azaindol-Derivate I: Asymmetrische Synthese einer neuen α-Aminosäure. Arch. Pharm. (Weinheim) 1988, 321, 505-507.
13. Anderson, P. L.; Hasak, J. P.; Kahle, A. D.; Paolella, N. A.; Shapiro, M. J. 1,3-Dipolar addition of pyridine N-imine to acetylenes and the use of 13-C NMR in several structural assignments. J. Heterocycl. Chem. 1981, 18, 1149-1152.
14. 1A Serotonin Ligands. J. Med. Chem. 1988, 31, 1968-1971.
15. Löber, S.; Aboul-Fadl, T.; Hübner, H.; Gmeiner, P. Di- and Trisubstituted Pyrazolo[1,5-a]pyridine Derivatives: Synthesis, Dopamine Receptor Binding and Ligand Efficacy. Bioorg. Med. Chem. Lett. 2002, 12, 633-636.
16. Corey, E. J.; Gilman, N. W.; Ganem, B. E. New Methods for the Oxidation of Aldehydes to Carboxylic Acids and Esters. J. Am. Chem. Soc. 1968, 90, 5616-5617.
17. (a) Carpino, L. A. 1-Hydroxy-7-azabenzotriazole. An Efficient Peptide Coupling Additive. J. Am. Chem. Soc. 1993, 115 4397-4398.
18. (b) Kienhöfer, A. 1-Hydroxy-7-azabenzotriazole (HOAt) and N-[(dimethylamino)-1H-1,2,3-triazolo- [4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU). Synlett 2001, 1811-1812.
19. Hayes, G.; Biden, T. J.; Selbie, L. A.; Shine J. Structural subtypes of the dopamine D2 receptor are functionally distinct: expression of the cloned D2A and D2B subtypes in a heterologous cell line. Mol. Endocrinol. 1992, 6, 920-926.
20. Sokoloff, P.; Andrieux, M.; Besançon, R.; Pilon, C.; Martres, M.-P.; Giros, B.; Schwartz, J.-C. Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor. Eur. J. Pharmacol. 1992, 225, 331-337.
21. Asghari, V.; Sanyal, S.; Buchwaldt, S.; Paterson, A.; Jovanovic, V.; Van Tol, H. H. M. Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J. Neurochem. 1995, 65, 1157-1165.
22. Hübner, H.; Haubmann, C.; Utz, W.; Gmeiner, P. Conjugated enynes as nonaromatic catechol bioisosteres: synthesis, binding experiments, and computational studies of novel dopamine receptor agonists recognizing preferentially the D3 subtype. J. Med. Chem. 2000, 43, 756-762.
23. (a) Mierau, J.; Schneider, F. J.; Ensinger, H. A.; Chio, C. L.; Lajiness, M. E.; Huff, R. M. Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur. J. Pharmacol. 1995, 290, 29-36.
24. (b) Hübner, H.; Kraxner, J.; Gmeiner, P. Cyanoindole derivatives as highly selective dopamine D4 receptor partial agonists: solid-phase synthesis, binding assays, and functional experiments. J. Med. Chem. 2000, 43, 4563-4569.
25. Chio, C.; Lajiness, M. E.; Huff, R. M. Activation of heterologously expressed D3 dopamine receptors: comparison with D2 dopamine receptors. Mol. Pharmacol. 1994, 45, 51-60.
26. Zanati, G.; Gaare, G.; Wolff, M. E. Heterocyclic steroids. 5. Sulfur, selenium, and tellurium 5α-androstane derivatives and their 7α-methylated congeners. J. Med. Chem. 1974, 17, 561-563.