Design, synthesis, radiolabeling, and in vivo evaluation of carbon-11 labeled N -[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a potential positron emission tomography tracer for the dopamine D4 receptors

Journal of Medicinal Chemistry

Volumn 53, Issue 20, 2010, Pages 7344-7355

  Lacivita, Enza ^a   De Giorgio, Paola ^a   Lee, Irene T ^b   Rodeheaver, Sean I ^b   Weiss, Bryan A ^b   Fracasso, Claudia ^c   Caccia, Silvio ^c   Berardi, Francesco ^a   Perrone, Roberto ^a   Zhang, Ming Rong ^d   Maeda, Jun ^d   Higuchi, Makoto ^d   Suhara, Tetsuya ^d   Schetz, John A ^b,e,f,g   Leopoldo, Marcello ^a  

^a UNIVERSITY OF BARI   (Italy)

^b UNIVERSITY OF NORTH TEXAS   (United States)

^c MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^d NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES   (Japan)

^e University of North Texas Health Science Center   (United States)

^f UNT Health Sciences Center   (United States)

^g UNIVERSITY OF TEXAS AT ARLINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [[4 (4 CHLOROPHENYL) 1 PIPERAZINYL]METHYL] 1H PYRROLO[2,3 B]PYRIDINE; 3 [[4 (4 IODOPHENYL) 1 PIPERAZINYL]METHYL] 1H PYRROLO[2,3 B]PYRIDINE; A 412997; ABT 724; ALPHA ADRENERGIC RECEPTOR; CARBON 11; DOPAMINE 4 RECEPTOR; FAUC 213; FLUORINE 18; L 7457870; N [2 [4 (1,2 BENZISOXAZOL 3 YL)PIPERAZIN 1 YL]ETHYL] 3 METHOXY BENZAMIDE; N [2 [4 (1,2 BENZISOXAZOL 3 YL)PIPERAZIN1 YL]ETHYL] 3 METHOXY BENZAMIDE; N [2 [4 (3 CYANOPYRIDIN 2 YL)PIPERAZIN 1 YL]ETHYL] 3 HYDROXYBENZAMIDE; N [2 [4 (3 CYANOPYRIDIN 2 YL)PIPERAZIN 1 YL]ETHYL] 3 METHOXYBENZAMIDE; N [2 [4 (3 CYANOPYRIDIN 2 YL)PIPERAZIN1 YL]ETHYL] 3 METHOXY BENZAMIDE; N [2 [4 (4 CHLOROPHENYL)PIPERAZIN 1 YL]ETHYL] 3 METHOXYBENZAMIDE; N [2 [4 (4 CYANOPHENYL)PIPERAZIN1 YL]ETHYL] 3 METHOXY BENZAMIDE; N [2 [4 (4 METHYLPHENYL)PIPERAZIN1 YL]ETHYL] 3 METHOXY BENZAMIDE; N [2 [4 (5 CHLOROPYRIDIN 2 YL)PIPERAZIN 1 YL]ETHYL] 4 FLUOROBENZAMIDE; SEROTONIN 1A RECEPTOR; SEROTONIN 2A RECEPTOR; SEROTONIN 2C RECEPTOR; SEROTONIN RECEPTOR; SONEPIPRAZOLE; TRACER; UNCLASSIFIED DRUG; YM 50001;

ARTICLE; BINDING AFFINITY; DRUG ACCUMULATION; DRUG DESIGN; DRUG PENETRATION; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; IN VIVO STUDY; ISOTOPE LABELING; LIGAND BINDING; LIPOPHILICITY; MALE; MOUSE; NONHUMAN; POSITRON EMISSION TOMOGRAPHY;

ANIMALS; BENZAMIDES; BRAIN; CARBON RADIOISOTOPES; CELL LINE; HUMANS; ISOTOPE LABELING; LIGANDS; MACACA MULATTA; MALE; MICE; NITRILES; PIPERAZINES; POSITRON-EMISSION TOMOGRAPHY; PYRIDINES; RADIOLIGAND ASSAY; RADIOPHARMACEUTICALS; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, DOPAMINE D4; RETINA; STRUCTURE-ACTIVITY RELATIONSHIP; TISSUE DISTRIBUTION;

EID: 77958513963     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100925m     Document Type: Article

References (67)

1. 4 receptor with high affinity for the antipsychotic clozapine Nature 1991, 350, 610-614 (Pubitemid 21912282)
2. 2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications Eur. J. Pharmacol. 1993, 236, 483-486
3. 4 receptor antagonists: review of structure-activity relationships Curr. Med. Chem.: Cent. Nerv. Syst. Agents 2002, 2, 259-274
4. 4 receptor antagonist, does not exhibit a neuroleptic-like profile in rodent behavioral tests J. Pharmacol. Exp. Ther. 1997, 283, 1256-1263
5. 4 dopamine antagonist group Arch. Gen. Psychiatry 1997, 54, 567-572
6. 4.4 receptor Br. J. Pharmacol. 1998, 124, 889-896
7. 4.4 receptors expressed in HEK293 cells Eur. J. Pharmacol. 1999, 372, R9-R10
8. Lober, S.; Hubner, 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
9. 4 receptor full antagonist, exhibits atypical antipsychotic properties in behavioural and neurochemical models of schizophrenia Psychopharmacology 2004, 175, 7-17
10. 4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial. Sonepiprazole study group Biol. Psychiatry 2004, 55, 445-451
11. 4DR) exon III polymorphism associated with the human personality trait of novelty seeking Nat. Genet. 1996, 12, 78-80
12. Ebstein, R. P.; Benjamin, J.; Belmaker, R. H. Personality and polymorphisms of genes involved in aminergic neurotransmission Eur. J. Pharmacol. 2000, 410, 205-214
13. 4 receptor-knock-out mice exhibit reduced exploration of novel stimuli J. Neurosci. 1999, 19, 9550-9556
14. Powell, S. B.; Paulus, M. P.; Hartman, D. S.; Godel, T.; Geyer, M. A. RO-10-5824 is a selective dopamine D4 receptor agonist that increases novel object exploration in C57 mice Neuropharmacology 2003, 44, 473-481
15. 4 receptor gene and attention deficit hyperactivity disorder Am. J. Psychiatry 2001, 158, 1052-1057
16. 4 alleles in children diagnosed with attention-deficit hyperactivity disorder Mol. Psychiatry 2003, 8, 536-545
17. 4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder Mol. Psychiatry 1996, 1, 121-124
18. 4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach Mol. Psychiatry 1998, 3, 38-41
19. 4 or SLC6A3 VNTRs Am. J. Med. Genet., Part B 2008, 147, 1470-1475
20. Shaw, P.; Gornick, M.; Lerch, J.; Addington, A.; Seal, J.; Greenstein, D.; Sharp, W.; Evans, A.; Giedd, J. N.; Castellanos, F. X.; Rapoport, J. L. Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder Arch. Gen. Psychiatry 2007, 64, 921-931
21. Schetz, J. A.; Sibley, D. R. Dopaminergic Neurotransmission. In Handbook of Contemporary Neuropharmacology; Sibley, D.; Hanin, I.; Kuhar, M.; Skolnick, P., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, 2007; pp 221 - 256.
22. 4 receptors in motor hyperactivity induced by neonatal 6-hydroxydopamine lesions in rats Neuropsychopharmacology 2001, 25, 624-632
23. Zhang, K.; Davids, E.; Tarazi, F. I.; Baldessarini, R. J. Serotonin transporter binding increases in caudate-putamen and nucleus accumbens after neonatal 6-hydroxydopamine lesions in rats: implications for motor hyperactivity Dev. Brain Res. 2002, 30, 135-138
24. 4 agonist, improves cognitive performance in rats Pharmacol., Biochem. Behav. 2005, 82, 148-155
25. 4 receptors by ABT-724 induces penile erection in rats Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 6758-6763
26. 3 receptor in rats and mice J. Pharmacol. Exp. Ther. 2009, 329, 210-217
27. 4 receptors in the rat retina Neuropharmacology 2003, 44, 1038-1046
28. 4 receptors coupled to adenylyl cyclase Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 12093-12097
29. 4 receptors J. Neurosci. 2002, 22, 2063-2073
30. 4 receptors antagonist for PET J. Labelled Compd. Radiopharm. 2000, 43, 359-374
31. 18F]fluorophenyl) piperazin-1-yl]methyl]-1 H -pyrrolo[2,3- b ]pyridine J. Labelled Compd. Radiopharm. 2002, 45, 687-696
32. 4 receptor in the primate brain with positron emission tomography Nucl. Med. Biol. 2000, 27, 707-714
33. 11C]methoxybenzamide Nucl. Med. Biol. 2002, 29, 233-241
34. 1 receptors Nucl. Med. Biol. 2002, 29, 469-476
35. 4 receptor imaging Bioorg. Med. Chem. 2004, 12, 5505-5513
36. 4 receptor ligands: discovery of an inverse agonist radioligand for PET J. Med. Chem. 2008, 51, 1800-1810
37. ClogP, version 4.0 (for Windows); BioByte Corp.: Claremont, CA.
38. Pike, V. W. PET radiotracers: crossing the blood-brain barrier and surviving metabolism Trends Pharmacol. Sci. 2009, 30, 431-340
39. Laruelle, M.; Slifstein, M.; Huang, Y. Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography Mol. Imaging Biol. 2003, 5, 363-375
40. Waterhouse, R. N. Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents Mol. Imaging Biol. 2003, 5, 376-389
41. 4 receptor Bioorg. Med. Chem. Lett. 1997, 7, 1327-1330
42. 4 ligand J. Med. Chem. 1998, 41, 4903-4909
43. 4 receptor ligand J. Med. Chem. 2000, 43, 270-277
44. 2+ channel blockers Bioorg. Med. Chem. 2004, 12, 3965-3970 (Pubitemid 38891358)
45. Ishizumi, K.; Kojima, A.; Antoku, F. Synthesis and anxiolytic activity of N-substituted cyclic imides (1 R*,2 S*,3 R*,4 S*)- N -[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3-bicyclo[2.2.1] heptanedicarboximide (tandospirone) and related compounds Chem. Pharm. Bull. 1991, 39, 2288-2300
46. 3 receptor ligands J. Med. Chem. 2002, 45, 5727-5735
47. 4 agonists Curr. Med. Chem. 2006, 13, 2981-2993
48. 4 receptor selective compounds and a distinct structure-affinity relationship for butyrophenones Eur. J. Pharmacol. 2008, 578, 123-136
49. Halldin, C.; Gulyás, B.; Langer, O.; Farde, L. Brain radioligands - state of the art and new trends Q. J. Nucl. Med. 2001, 45, 139-152
50. 3H]NGD 94-1 J. Pharmacol. Exp. Ther. 1997, 282, 1020-1027
51. 4 dopamine receptor probe, accumulates in prefrontal cortex and hippocampus of non-human primate brain Synapse 2000, 37, 232-244
52. 3H]-YM-09151-2 binding sites in human brain postmortem Neurochem. Int. 2009, 55, 643-647
53. Inoue, O.; Kobayashi, K.; Gee, A. Changes in apparent rates of receptor binding in the intact brain in relation to the heterogeneity of reaction environments Crit. Rev. Neurobiol. 1999, 13, 199-225
54. Caccia, S. N-Dealkylation of arylpiperazine derivatives: disposition and metabolism of the 1-aryl-piperazines formed Curr. Drug Metab. 2007, 8, 612-622
55. Steuer, H.; Jaworski, A.; Stoll, D.; Schlosshauer, B. In vitro model of the outer blood-retina barrier Brain Res. Protoc. 2004, 13, 26-36
56. Kyle, D. J.; Sun, Q. Preparation of Piperazine Compounds as VR1 Inhibitors. PCT Int. Appl. WO 2005012287, 2005
57. Chem. Abstr. 2005, 142, 198104.
58. 3 receptors J. Med. Chem. 2006, 49, 358-365 and references cited therein (Pubitemid 43077348)
59. a detrmination of water-insoluble drugs in organic solvent-water mixtures J. Pharm. Biomed. Anal. 1999, 20, 631-641
60. 11C]Ro15-4513 and its application in an extremely low concentration region to an ARG study Nucl. Med. Biol. 2003, 30, 335-343
61. 2 dopamine receptors is modulated by changes in local dynamics produced by sodium binding J. Pharmacol. Exp. Ther. 2009, 328, 40-54
62. 2 dopamine receptor regulate selective ligand function and affinity J. Neurochem. 2009, 110, 45-57
63. 2C receptor subtypes Bioorg. Med. Chem. 2010, 18, 4783-4792
64. 4 receptor interact with a common receptor microdomain Mol. Pharmacol. 2004, 66, 1491-1499
65. 50) of an enzymatic reaction Biochem. Pharmacol. 1973, 22, 3099-3108
66. Watanabe, M.; Okada, H.; Shimizu, K.; Omura, T.; Yoshikawa, E.; Kosugi, T.; Mori, S.; Yamashita, T. A high resolution animal PET scanner using compact PS-PMT detectors IEEE Trans. Nucl. Sci. 1997, 44, 1277-1282
67. 11C]Ro15-4513 using positron emission tomography Synapse 2003, 47, 200-208