Evaluation of 18F-labeled benzodioxine piperazine-based dopamine D 4 receptor ligands: Lipophilicity as a determinate of nonspecific binding

Journal of Medicinal Chemistry

Volumn 54, Issue 24, 2011, Pages 8343-8352

  Kügler, Fabian ^a   Sihver, Wiebke ^a   Ermert, Johannes ^a   Hübner, Harald ^b   Gmeiner, Peter ^b   Prante, Olaf ^b   Coenen, Heinz H ^a  

^a FORSCHUNGSZENTRUM JÜLICH   (Germany)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2,3 DIHYDROBENZO[1,4]DIOXIN 6 YL) 4 (4 FLUORO 3 METHOXYBENZYL)PIPERAZINE; 1 (2,3 DIHYDROBENZO[1,4]DIOXIN 6 YL) 4 (4 FLUOROBENZYL) PIPERAZINE; 1 (2,3 DIHYDROBENZO[B][1,4]DIOXIN 6 YL) 4 [(6 FLUOROPYRIDIN 3 YL)METHYL]PIPERAZINE; 5 [4 (2,3 DIHYDROBENZO[1,4]DIOXIN 6 YL)PIPERAZIN 1 YLMETHYL] 2 FLUOROPHENOL; DOPAMINE 1 RECEPTOR; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; DOPAMINE 4 RECEPTOR; FLUORINE 18; PIPERAZINE DERIVATIVE; RADIOLIGAND; UNCLASSIFIED DRUG; 1 (2,3 DIHYDROBENZO(B)(1,4)DIOXIN 6 YL) 4 ((6 FLUOROPYRIDIN 3 YL)METHYL)PIPERAZINE; 1-(2,3-DIHYDROBENZO(B)(1,4)DIOXIN-6-YL)-4-((6-FLUOROPYRIDIN-3-YL)METHYL)PIPERAZINE; DIOXANE DERIVATIVE; FLUORINE; LIGAND; RADIOPHARMACEUTICAL AGENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; AUTORADIOGRAPHY; BINDING AFFINITY; BRAIN CORTEX; CEREBELLUM; CHEMICAL STRUCTURE; DRUG DISTRIBUTION; DRUG STABILITY; FEMALE; HIPPOCAMPUS; IN VITRO STUDY; IN VIVO STUDY; INFERIOR COLLICULUS; LIPOPHILICITY; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; POSITRON EMISSION TOMOGRAPHY; RAT; RECEPTOR BINDING; SUPERIOR COLLICULUS; ANIMAL; BRAIN; CHEMISTRY; HUMAN; METABOLISM; RADIOASSAY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TISSUE DISTRIBUTION; WISTAR RAT;

ANIMALS; AUTORADIOGRAPHY; BRAIN; DIOXANES; FLUORINE RADIOISOTOPES; HUMANS; LIGANDS; MICE; PIPERAZINES; RADIOLIGAND ASSAY; RADIOPHARMACEUTICALS; RATS; RATS, WISTAR; RECEPTORS, DOPAMINE D4; STRUCTURE-ACTIVITY RELATIONSHIP; TISSUE DISTRIBUTION;

EID: 84055211844     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200762g     Document Type: Article

References (55)

1. 4 receptor with high affinity for the antipsychotic clozapine. Nature 1991, 350, 610-614.
2. 2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications. Eur. J. Pharmacol. 1993, 236, 483-486.
3. 4 receptor variants in the human population. Nature 1992, 358, 149-152.
4. 4 (DRD4) gene locus. Am. J. Hum. Genet. 1992, 74, 931-944.
5. 3H]NGD-94-1 study. Mol. Psychiatry 1998, 3, 528-533.
6. 3H-NGD 94-1. J. Pharmacol. Exp. Ther. 1997, 282, 1020-1027.
7. 4 receptor gene using BAC transgenic mice. Eur. J. Neurosci. 2006, 24, 2429-2438.
8. Oak, J. N.; Oldenhof, J.; Van Tol, H. H. The dopamine D(4) receptor: one decade of research. Eur. J. Pharmacol. 2000, 405, 303-327.
9. 4 receptor. Mol. Brain Res. 1995, 29, 157-162.
10. Lidow, M. S.; Wang, F.; Cao, Y.; Goldman-Rakic, P. S. Layer V neurons bear the majority of mRNAs encoding the five distinct dopamine receptor subtypes in the primate prefrontal cortex. Synapse 1998, 28, 10-20.
11. 4 dopamine receptor protein in the CNS using anti-receptor antisera. Brain Res. 1997, 752, 26-34.
12. 4 sites in schizophrenic brains. Eur. J. Pharmacol. 1996, 314, R3-5.
13. Reynolds, G. P.; Mason, S. L. Absence of detectable striatal dopamine D4 receptors in drug-treated schizophrenia. Eur. J. Pharmacol. 1995, 281, R5-R6.
14. 2-like Receptors. In The Dopamine Receptors, 2nd ed.; Neve, K. A., Ed.; Humana Press, Springer Verlag: Heidelberg, Germany, 2010.
15. 4-selective drugs: probes, models and candidates. Trends Pharmacol. Sci. 2011, 32, 148-157.
16. 4 agonists. J. Med. Chem. 1997, 40, 1771-1772.
17. 4 receptor ligands leading to the complete antagonist 2-[4-(4-chlorophenyl)piperazine-1-yl]methylpyrazol[1,5- a]pyridine (FAUC 213). J. Med. Chem. 2001, 44, 2691-2694.
18. 4 receptor antagonist. Neuropharmacology 2005, 49, 112-121.
19. 4 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.
20. 4 receptor gene (DRD4) contribute to individual differences in human sexual behavior: desire, arousal and sexual function. Mol. Psychiatry 2006, 11, 782-786.
21. 4 receptor agonist, induces penile erection when injected into the paraventricular nucleus of male rats. Neurosci. Lett. 2005, 379, 59-62.
22. 4 receptor: biochemical and signalling properties. Cell. Mol. Life Sci. 2010, 67, 1971-1986.
23. Hsieh, G. C.; Hollingsworth, P. R.; Martino, B.; Chang, R.; Terranova, M. A.; O'Neill, A. B.; Lynch, J. J.; Moreland, R. B.; Donnelly-Roberts, D. L.; Kolasa, T.; Mikusa, J. P.; McVey, J. M.; Marsh, K. C.; Sullivan, J. P.; Brioni, J. D. Central mechanisms regulating penile erection in conscious rats: the dopaminergic systems related to the proerectile effect of apomorphine. J. Pharmacol. Exp. Ther. 2004, 308, 330-338.
24. 4 receptor agonist and radioligand. Bioorg. Med. Chem. Lett. 2004, 14, 5095-5098.
25. 11C]SDZ GLC 756. Synapse 1998, 30, 341-350.
26. 11C]methoxybenz-amide. Nucl. Med. Biol. 2002, 29, 233-241.
27. 4 receptor imaging. Bioorg. Med. Chem. 2004, 12, 5505-5513.
28. 4 receptor interact with a common receptor microdomain. Mol. Pharmacol. 2004, 66, 1491-1499.
29. Wang, Y.; Mathis, C. A.; Huang, G. F.; Debnath, M. L.; Holt, D. P.; Shao, L.; Klunk, W. E. Effects of lipophilicity on the affinity and nonspecific binding of iodinated benzothiazole derivatives. J. Mol. Neurosci. 2003, 20, 255-260.
30. Sebai, S.; Baciu, M.; Ces, O.; Clarke, J.; Cunningham, V.; Gunn, R.; Law, R.; Mulet, X.; Parker, C.; Plisson, C.; Templer, R.; Gee, A. To lipophilicity and beyond: towards a deeper understanding of radioligand non-specific binding. NeuroImage 2006, 31, T44-T186.
31. Wilson, A.; Garcia, A.; Chestakova, A.; Houle, S. How good is the correlation between lipophilicity/phospholipicity and non-specific binding. NeuroImage 2004, 22, T61-T200.
32. 18F-β-carboline alkaloids as PET ligands. J. Labelled Compd. Radiopharm. 2008, 51, 277-282.
33. Hodgetts, K. J.; Kieltyka, A.; Brodbeck, R.; Tran, J. N.; Wasley, J. W.; Thurkauf, A. 6-(4-Benzylpiperazin-1-yl)benzodioxanes as selective ligands at cloned primate dopamine D(4) receptors. Bioorg. Med. Chem. 2001, 9, 3207-3213.
34. 4 receptor ligands: discovery of an inverse agonist radioligand for PET. J. Med. Chem. 2008, 51, 1800-1810.
35. Liu, K. G.; Robichaud, A. J. A general and convenient synthesis of N-aryl piperazines. Tetrahedron Lett. 2005, 46, 7921.
36. 4 receptors. Unpublished results.
37. 2 receptor are functionally distinct: expression of the cloned D2A and D2B subtypes in a heterologous cell line. Mol. Endocrinol. 1992, 6, 920-926.
38. 3) as a target for neuroleptics. Nature 1990, 347, 146-151.
39. Asghari, V.; Sanyal, S.; Buchwaldt, S.; Paterson, A.; Jovanovic, V.; Vantol, H. H. M. Modulation of intracellular cyclic-Amp levels by different human dopamine D4 receptor variants. J. Neurochem. 1995, 65, 1157-1165.
40. 3 subtype. J. Med. Chem. 2000, 43, 756-762.
41. Schlotter, K.; Boeckler, F.; Hübner, H.; Gmeiner, P. Fancy bioisosteres: metallocene-derived G-protein-coupled receptor ligands with subnanomolar binding affinity and novel selectivity profiles. J. Med. Chem. 2005, 48, 3696-3699.
42. 4 receptor partial agonists: solid-phase synthesis, binding assays, and functional experiments. J. Med. Chem. 2000, 43, 4563-4569.
43. 2 dopamine receptors. Mol. Pharmacol. 1994, 45, 51-60.
44. MarvinSketch Demo, version 5.1.4; ChemAxon: Budapest, Hungary, 2009; http://www.chemaxon.com/marvin/sketch/index.jsp.
45. ALOGPS, version 2.1; Virtual Computational Chemistry Laboratory, 2009; www.vcclab.org/lab/alogps/start.html
46. OECD Guideline for the Testing of Chemicals; OECD: Paris, France, 1989; http://www.oecd.org/dataoecd/17/36/1948177.pdf.
47. Mendel, C. M.; Mendel, D. B. "Non-specific" binding. Biochem. J. 1985, 228, 269-272.
48. Prante, O.; Hocke, C.; Löber, S.; Hübner, H.; Gmeiner, P.; Kuwert, T. Tissue distribution of radioiodinated FAUC113. Nuklearmedizin 2006, 45, 41-48.
49. 2-like receptors are expressed in pancreatic beta cells and mediate inhibition of insulin secretion. J. Biol. Chem. 2005, 280, 36824-36832.
50. Qaim, S. M.; Clark, J. C.; Crouzel, C.; Guillaume, M.; Helmecke, H. J.; Nebeling, B.; Pike, V. W.; Stöcklin, G. In Radiopharmaceuticals for PET; Stöcklin, G., Pike, V. W., Eds.; Kluwer Academic Publishers, Dordrecht, The Netherlands, 1993; pp 15-26.
51. 18F]-fluoroheptadecanoic acid in high yields via aminopolyether supported, nucleophilic fluorination. J. Labelled Compd. Radiopharm. 1986, 23, 455-466.
52. Lowry, O. H.; Rosebrough, N. J.; Farr, A. L.; Randall, R. J. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 1951, 193, 265-275.
53. 4 receptors. Eur. J. Pharmacol. 1995, 290, 29-36.
54. 50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
55. Zhang, K.; Weiss, N. T.; Tarazi, F. I.; Kula, N. S.; Baldessarini, R. J. Effects of alkylating agents on dopamine D(3) receptors in rat brain: selective protection by dopamine. Brain Res. 1999, 847, 32-37.