Structural modifications of neuroprotective anti-parkinsonian (-)-N6-(2-(4-(biphenyl-4-yl)piperazin-1-yl)-ethyl)-N6-propyl-4,5,6, 7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264): An effort toward the improvement of in vivo efficacy of the parent molecule

Journal of Medicinal Chemistry

Volumn 57, Issue 4, 2014, Pages 1557-1572

  Modi, Gyan ^a   Antonio, Tamara ^b   Reith, Maarten ^b   Dutta, Aloke ^a  

^a WAYNE STATE UNIVERSITY   (United States)

^b NEW YORK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIPARKINSON AGENT; BETA CYCLODEXTRIN DERIVATIVE; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; DOPAMINE 3 RECEPTOR STIMULATING AGENT; N6 [2 [4 (BIPHENYL 4 YL)PIPERAZIN 1 YL] ETHYL] N6 PROPYL 4,5,6,7 TETRAHYDROBENZO[D]THIAZOLE 2,6 DIAMINE; SCAVENGER; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BINDING; DRUG EFFICACY; DRUG STRUCTURE; HUMAN; HUMAN CELL; IN VIVO STUDY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; BIPHENYL COMPOUNDS; CELL LINE; DISEASE MODELS, ANIMAL; MICE; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE; PIPERAZINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

EID: 84896861124     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm401883v     Document Type: Article

References (56)

1. Braak, H.; Del Tredici, K.; Rub, U.; de Vos, R. A.; Jansen Steur, E. N.; Braak, E. Staging of brain pathology related to sporadic Parkinson's disease Neurobiol. Aging 2003, 24, 197-211
2. Paulus, W.; Jellinger, K. The neuropathologic basis of different clinical subgroups of Parkinson's disease J. Neuropathol. Exp. Neurol. 1991, 50, 743-755
3. Sherer, T. B.; Betarbet, R.; Greenamyre, J. T. Pathogenesis of Parkinson's disease Curr. Opin. Investig. Drugs 2001, 2, 657-662
4. Wooten, G. F. In Movement Disorders: Neurologic Principles and Practice; Watts, R. L.; Koller, W. C., Eds.; McGraw-Hill: New York, 1997; pp 153-160.
5. Betarbet, R.; Sherer, T. B.; MacKenzie, G.; Garcia-Osuna, M.; Panov, A. V.; Greenamyre, J. T. Chronic systemic pesticide exposure reproduces features of Parkinson's disease Nat. Neurosci. 2000, 3, 1301-1306
6. Dawson, T. M.; Dawson, V. L. Molecular pathways of neurodegeneration in Parkinson's disease Science 2003, 302, 819-822
7. Fink, A. L. The aggregation and fibrillation of alpha-synuclein Acc. Chem. Res. 2006, 39, 628-634
8. Marras, C.; Lang, A. E. Measuring motor complications in clinical trials for early Parkinson's disease J. Neurol. Neurosurg. Psychiatry 2003, 74, 143-146
9. Marsden, C. D.; Parkes, J. D. "On-off" effects in patients with Parkinson's disease on chronic levodopa therapy Lancet 1976, 1, 292-296
10. d'Ischia, M.; Prota, G. Biosynthesis, structure, and function of neuromelanin and its relation to Parkinson's disease: a critical update Pigment Cell Res. 1997, 10, 370-376
11. Sokoloff, P.; Giros, B.; Martres, M. P.; Andrieux, M.; Besancon, R.; Pilon, C.; Bouthenet, M. L.; Souil, E.; Schwartz, J. C. Localization and function of the D3 dopamine receptor Arzneimittelforschung 1992, 42, 224-230
12. Giros, B.; Martres, M. P.; Sokoloff, P.; Schwartz, J. C. [Gene cloning of human dopaminergic D3 receptor and identification of its chromosome] C. R. Acad. Sci. III 1990, 311, 501-508
13. Gurevich, E. V.; Joyce, J. N. Distribution of dopamine D3 receptor expressing neurons in the human forebrain: comparison with D2 receptor expressing neurons Neuropsychopharmacology 1999, 20, 60-80
14. Park, B. H.; Fishburn, C. S.; Carmon, S.; Accili, D.; Fuchs, S. Structural organization of the murine D3 dopamine receptor gene J. Neurochem. 1995, 64, 482-486
15. Missale, C.; Nash, S. R.; Robinson, S. W.; Jaber, M.; Caron, M. G. Dopamine receptors: from structure to function Physiol. Rev. 1998, 78, 189-225
16. Du, F.; Li, R.; Huang, Y.; Li, X.; Le, W. Dopamine D3 receptor-preferring agonists induce neurotrophic effects on mesencephalic dopamine neurons Eur. J. Neurosci. 2005, 22, 2422-2430
17. Joyce, J. N.; Millan, M. J. Dopamine D3 receptor agonists for protection and repair in Parkinson's disease Curr. Opin. Pharmacol. 2007, 7, 100-105
18. Banala, A. K.; Levy, B. A.; Khatri, S. S.; Furman, C. A.; Roof, R. A.; Mishra, Y.; Griffin, S. A.; Sibley, D. R.; Luedtke, R. R.; Newman, A. H. N-(3-fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl)piperazine-1-yl)butyl) arylcarboxamides as selective dopamine D3 receptor ligands: critical role of the carboxamide linker for D3 receptor selectivity J. Med. Chem. 2011, 54, 3581-3594
19. Boeckler, F.; Gmeiner, P. The structural evolution of dopamine D3 receptor ligands: structure-activity relationships and selected neuropharmacological aspects Pharmacol. Ther. 2006, 112, 281-333
20. Boeckler, F.; Ohnmacht, U.; Lehmann, T.; Utz, W.; Hubner, H.; Gmeiner, P. CoMFA and CoMSIA investigations revealing novel insights into the binding modes of dopamine D3 receptor agonists J. Med. Chem. 2005, 48, 2493-2508
21. Ehrlich, K.; Gotz, A.; Bollinger, S.; Tschammer, N.; Bettinetti, L.; Harterich, S.; Hubner, H.; Lanig, H.; Gmeiner, P. Dopamine D2, D3, and D4 selective phenylpiperazines as molecular probes to explore the origins of subtype specific receptor binding J. Med. Chem. 2009, 52, 4923-4935
22. Elsner, J.; Boeckler, F.; Heinemann, F. W.; Hubner, H.; Gmeiner, P. Pharmacophore-guided drug discovery investigations leading to bioactive 5-aminotetrahydropyrazolopyridines. Implications for the binding mode of heterocyclic dopamine D3 receptor agonists J. Med. Chem. 2005, 48, 5771-5779
23. Gil-Mast, S.; Kortagere, S.; Kota, K.; Kuzhikandathil, E. V. An Amino Acid Residue in the Second Extracellular Loop Determines the Agonist-Dependent Tolerance Property of the Human D3 Dopamine Receptor ACS Chem. Neurosci. 2013, 4, 940-951
24. Grundt, P.; Carlson, E. E.; Cao, J.; Bennett, C. J.; McElveen, E.; Taylor, M.; Luedtke, R. R.; Newman, A. H. Novel heterocyclic trans olefin analogues of N -{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl}arylcarboxamides as selective probes with high affinity for the dopamine D3 receptor J. Med. Chem. 2005, 48, 839-848
25. Varady, J.; Wu, X.; Fang, X.; Min, J.; Hu, Z.; Levant, B.; Wang, S. Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor: discovery of novel and potent D3 ligands through a hybrid pharmacophore- and structure-based database searching approach J. Med. Chem. 2003, 46, 4377-4392
26. Newman, A. H.; Beuming, T.; Banala, A. K.; Donthamsetti, P.; Pongetti, K.; LaBounty, A.; Levy, B.; Cao, J.; Michino, M.; Luedtke, R. R.; Javitch, J. A.; Shi, L. Molecular determinants of selectivity and efficacy at the dopamine D3 receptor J. Med. Chem. 2012, 55, 6689-6699
27. Zhao, Y.; Lu, X.; Yang, C. Y.; Huang, Z.; Fu, W.; Hou, T.; Zhang, J. Computational modeling toward understanding agonist binding on dopamine 3 J. Chem. Inf. Model. 2010, 50, 1633-1643
28. Chien, E. Y.; Liu, W.; Zhao, Q.; Katritch, V.; Han, G. W.; Hanson, M. A.; Shi, L.; Newman, A. H.; Javitch, J. A.; Cherezov, V.; Stevens, R. C. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist Science 2010, 330, 1091-1095
29. Jenner, P. Oxidative stress in Parkinson's disease Ann. Neurol. 2003, 53 (Suppl 3) S26-36-discussion S36-28
30. Berg, D.; Gerlach, M.; Youdim, M. B.; Double, K. L.; Zecca, L.; Riederer, P.; Becker, G. Brain iron pathways and their relevance to Parkinson's disease J. Neurochem. 2001, 79, 225-236
31. Ostrerova-Golts, N.; Petrucelli, L.; Hardy, J.; Lee, J. M.; Farer, M.; Wolozin, B. The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity J. Neurosci. 2000, 20, 6048-6054
32. Cappai, R.; Leck, S. L.; Tew, D. J.; Williamson, N. A.; Smith, D. P.; Galatis, D.; Sharples, R. A.; Curtain, C. C.; Ali, F. E.; Cherny, R. A.; Culvenor, J. G.; Bottomley, S. P.; Masters, C. L.; Barnham, K. J.; Hill, A. F. Dopamine promotes alpha-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway FASEB J. 2005, 19, 1377-1379
33. Meng, X.; Munishkina, L. A.; Fink, A. L.; Uversky, V. N. Effects of Various Flavonoids on the alpha-Synuclein Fibrillation Process Parkinson's Dis. 2010, 2010, 650794
34. Paleologou, K. E.; Irvine, G. B.; El-Agnaf, O. M. Alpha-synuclein aggregation in neurodegenerative diseases and its inhibition as a potential therapeutic strategy Biochem. Soc. Trans. 2005, 33, 1106-1110
35. Li, H. T.; Lin, D. H.; Luo, X. Y.; Zhang, F.; Ji, L. N.; Du, H. N.; Song, G. Q.; Hu, J.; Zhou, J. W.; Hu, H. Y. Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein. Implication for dopaminergic neurodegeneration FEBS J. 2005, 272, 3661-3672
36. Cavalli, A.; Bolognesi, M. L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases J. Med. Chem. 2008, 51, 347-372
37. Biswas, S.; Hazeldine, S.; Ghosh, B.; Parrington, I.; Kuzhikandathil, E.; Reith, M. E.; Dutta, A. K. Bioisosteric heterocyclic versions of 7-{[2-(4-phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen- 2- ol: identification of highly potent and selective agonists for dopamine D3 receptor with potent in vivo activity J. Med. Chem. 2008, 51, 3005-3019
38. Biswas, S.; Zhang, S.; Fernandez, F.; Ghosh, B.; Zhen, J.; Kuzhikandathil, E.; Reith, M. E.; Dutta, A. K. Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}- 5,6,7,8-tetrahydronaphthalen-2-o l analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration of action J. Med. Chem. 2008, 51, 101-117
39. Ghosh, B.; Antonio, T.; Reith, M. E.; Dutta, A. K. Discovery of 4-(4-(2-((5-Hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)ethyl) piperaz in-1-yl)quinolin-8-ol and its analogues as highly potent dopamine D2/D3 agonists and as iron chelator: in vivo activity indicates potential application in symptomatic and neuroprotective therapy for Parkinson's disease J. Med. Chem. 2010, 53, 2114-2125
40. Ghosh, B.; Antonio, T.; Zhen, J.; Kharkar, P.; Reith, M. E.; Dutta, A. K. Development of (S)-N6-(2-(4-(isoquinolin-1-yl)piperazin-1-yl)ethyl)-N6-propyl- 4,5,6,7-tetrahydro benzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor preferring agonist: potent in vivo activity in Parkinson's disease animal models J. Med. Chem. 2010, 53, 1023-1037
41. Dutta, A. K.; Venkataraman, S. K.; Fei, X. S.; Kolhatkar, R.; Zhang, S.; Reith, M. E. Synthesis and biological characterization of novel hybrid 7-[[2-(4-phenyl-piperazin-1-yl)-ethyl]-propyl-amino]-5,6,7,8-tetrahydro-na phthalen-2-ol and their heterocyclic bioisosteric analogues for dopamine D2 and D3 receptors Bioorg. Med. Chem. 2004, 12, 4361-4373
42. Biswas, S.; Hazeldine, S.; Ghosh, B.; Parrington, I.; Kuzhikandathil, E.; Reith, M. E.; Dutta, A. K. Bioisosteric heterocyclic versions of 7-{[2-(4-phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphth alen-2-ol: identification of highly potent and selective agonists for dopamine D3 receptor with potent in vivo activity J. Med. Chem. 2008, 51, 3005-3019
43. Biswas, S.; Zhang, S.; Fernandez, F.; Ghosh, B.; Zhen, J.; Kuzhikandathil, E.; Reith, M. E.; Dutta, A. K. Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}- 5,6,7,8-tetrahydronaphtha len-2-ol analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration of action J. Med. Chem. 2008, 51, 101-117
44. Johnson, M.; Antonio, T.; Reith, M. E.; Dutta, A. K. Structure-activity relationship study of N(6)-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N(6)- propyl-4,5,6,7-tetrahydroben zo[d]thiazole-2,6-diamine analogues: development of highly selective D3 dopamine receptor agonists along with a highly potent D2/D3 agonist and their pharmacological characterization J. Med. Chem. 2012, 55, 5826-5840
45. Li, C.; Biswas, S.; Li, X.; Dutta, A. K.; Le, W. Novel D3 dopamine receptor-preferring agonist D-264: Evidence of neuroprotective property in Parkinson's disease animal models induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine and lactacystin J. Neurosci. Res. 2010, 88, 2513-2523
46. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Adv. Drug Delivery Rev. 2001, 46, 3-26
47. Jensen, M. S.; Hoerrner, R. S.; Li, W.; Nelson, D. P.; Javadi, G. J.; Dormer, P. G.; Cai, D.; Larsen, R. D. Efficient synthesis of a GABA A alpha2,3-selective allosteric modulator via a sequential Pd-catalyzed cross-coupling approach J. Org. Chem. 2005, 70, 6034-6039
48. Li, W.; Nelson, D. P.; Jensen, M. S.; Hoerrner, R. S.; Cai, D.; Larsen, R. D.; Reider, P. J. An improved protocol for the preparation of 3-pyridyl- and some arylboronic acids J. Org. Chem. 2002, 67, 5394-5397
49. Liu, K. G.; Robichaud, A. J. A general and convenient synthesis of N-aryl piperazines Tetrahedron Lett. 2005, 46, 7921-7922
50. Doll, M. K.; Nichols, D. E.; Kilts, J. D.; Prioleau, C.; Lawler, C. P.; Lewis, M. M.; Mailman, R. B. Synthesis and dopaminergic properties of benzo-fused analogues of quinpirole and quinelorane J. Med. Chem. 1999, 42, 935-940
51. Kortagere, S.; Cheng, S. Y.; Antonio, T.; Zhen, J.; Reith, M. E.; Dutta, A. K. Interaction of novel hybrid compounds with the D3 dopamine receptor: Site-directed mutagenesis and homology modeling studies Biochem. Pharmacol. 2011, 81, 157-163
52. Carlsson, A.; Lindqvist, M.; Magnusson, T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists Nature 1957, 180, 1200
53. Skalisz, L. L.; Beijamini, V.; Joca, S. L.; Vital, M. A.; Da Cunha, C.; Andreatini, R. Evaluation of the face validity of reserpine administration as an animal model of depression - Parkinson's disease association Prog. Neuropsychopharmacol. Biol. Psychiatry 2002, 26, 879-883
54. Ungerstedt, U.; Arbuthnott, G. W. Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system Brain Res. 1970, 24, 485-493
55. Santra, S.; Xu, L.; Shah, M.; Johnson, M.; Dutta, A. D-512 and D-440 as Novel Multifunctional Dopamine Agonists: Characterization of Neuroprotection Properties and Evaluation of In Vivo Efficacy in a Parkinson's Disease Animal Model ACS Chem. Neurosci. 2013, 4, 1382-1392
56. Zhen, J.; Antonio, T.; Dutta, A. K.; Reith, M. E. Concentration of receptor and ligand revisited in a modified receptor binding protocol for high-affinity radioligands: [3H]Spiperone binding to D2 and D3 dopamine receptors J. Neurosci. Methods 2010, 188, 32-38