Molecular determinants of selectivity and efficacy at the dopamine D3 receptor

Journal of Medicinal Chemistry

Volumn 55, Issue 15, 2012, Pages 6689-6699

  Newman, Amy Hauck ^a   Beuming, Thijs ^b   Banala, Ashwini K ^a   Donthamsetti, Prashant ^c   Pongetti, Katherine ^d   Labounty, Alex ^d   Levy, Benjamin ^a   Cao, Jianjing ^a   Michino, Mayako ^e   Luedtke, Robert R ^d   Javitch, Jonathan A ^c   Shi, Lei ^e  

^a NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

^b SCHRÖDINGER INC   (United States)

^c Columbia University College of Physicians and Surgeons ^*  (United States)

^d UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER   (United States)

^e WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2 METHOXYPHENYL) 4 METHYLPIPERAZINE; 1 (2,3 DICHLOROPHENYL) 4 METHYLPIPERAZINE; 1 (2,3 DICHLOROPHENYL) 4 PROPYLPIPERAZINE; 1 BUTYL 4 (2,3 DICHLOROPHENYL) 4 PROPYLPIPERAZINE; 1 BUTYL 4 (2,3 METHOXYPHENYL) 4 PROPYLPIPERAZINE; 2 [4 (2,3 DICHLOROPHENYL)PIPERAZIN 1 YL]ETHANOL; DOPAMINE 3 RECEPTOR; DOPAMINE 3 RECEPTOR STIMULATING AGENT; ETICLOPRIDE; N [4 [4 (2,3 DICHLOROPHENYL)PIPERAZIN 1 YL)BUTYL] 1H INDOLE 2 CARBOXAMIDE; N BUTYL 1H INDOLE 2 CARBOXAMIDE; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CONTROLLED STUDY; DRUG DESIGN; DRUG EFFICACY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; HUMAN; HUMAN CELL; SUBSTITUTION REACTION;

COMPUTER SIMULATION; HEK293 CELLS; HUMANS; MOLECULAR CONFORMATION; MOLECULAR DYNAMICS SIMULATION; PIPERAZINES; RADIOLIGAND ASSAY; RECEPTORS, DOPAMINE D2; RECEPTORS, DOPAMINE D3; STATIC ELECTRICITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84864938692     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300482h     Document Type: Article

References (47)

1. Lober, S.; Hubner, H.; Tschammer, N.; Gmeiner, P. Recent advances in the search for D(3)- and D(4)-selective drugs: probes, models and candidates Trends Pharmacol. Sci. 2011, 32, 148-157
2. Sokoloff, P.; Giros, B.; Martres, M. P.; Bouthenet, M. L.; Schwartz, J. C. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics Nature 1990, 347, 146-151
3. Levant, B. The D3 dopamine receptor: neurobiology and potential clinical relevance Pharmacol. Rev. 1997, 49, 231-252
4. 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
5. Heidbreder, C. A.; Newman, A. H. Current perspectives on selective dopamine D(3) receptor antagonists as pharmacotherapeutics for addictions and related disorders Ann. N.Y. Acad. Sci. 2010, 1187, 4-34
6. Vangveravong, S.; Zhang, Z.; Taylor, M.; Bearden, M.; Xu, J.; Cui, J.; Wang, W.; Luedtke, R. R.; Mach, R. H. Synthesis and characterization of selective dopamine D receptor ligands using aripiprazole as the lead compound Bioorg. Med. Chem. 2011, 19, 3502-3511
7. 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 Arzneim. Forsch. 1992, 42, 224-230
8. Micheli, F. Recent advances in the development of dopamine D3 receptor antagonists: a medicinal chemistry perspective ChemMedChem 2011, 6, 1152-1162
9. Found 12 studies with search of: GSK598809; National Institutes of Health: Bethesda, MD; http://clinicaltrials.gov/ct2/results?term=GSK598809 (Accessed 5/3/2012).
10. Newman, A. H.; Grundt, P.; Cyriac, G.; Deschamps, J. R.; Taylor, M.; Kumar, R.; Ho, D.; Luedtke, R. R. N -(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl)heterobiarylcarboxamides with functionalized linking chains as high affinity and enantioselective D3 receptor antagonists J. Med. Chem. 2009, 52, 2559-2270
11. Grundt, P.; Prevatt, K. M.; Cao, J.; Taylor, M.; Floresca, C. Z.; Choi, J. K.; Jenkins, B. G.; Luedtke, R. R.; Newman, A. H. Heterocyclic analogues of N -(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)butyl)arylcarboxamides with functionalized linking chains as novel dopamine D3 receptor ligands: potential substance abuse therapeutic agents J. Med. Chem. 2007, 50, 4135-4146
12. 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
13. 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
14. Shi, L.; Javitch, J. A. The binding site of aminergic G protein-coupled receptors: the transmembrane segments and second extracellular loop Annu. Rev. Pharmacol. Toxicol. 2002, 42, 437-467
15. Carlsson, J.; Coleman, R. G.; Setola, V.; Irwin, J. J.; Fan, H.; Schlessinger, A.; Sali, A.; Roth, B. L.; Shoichet, B. K. Ligand discovery from a dopamine D(3) receptor homology model and crystal structure Nature Chem. Biol. 2011, 7, 769-778
16. Mohr, K.; Trankle, C.; Kostenis, E.; Barocelli, E.; De Amici, M.; Holzgrabe, U. Rational design of dualsteric GPCR ligands: quests and promise Br. J. Pharmacol. 2010, 159, 997-1008
17. Leach, K.; Davey, A. E.; Felder, C. C.; Sexton, P. M.; Christopoulos, A. The role of transmembrane domain 3 in the actions of orthosteric, allosteric, and atypical agonists of the M4 muscarinic acetylcholine receptor Mol. Pharmacol. 2011, 79, 855-865
18. Rasmussen, S. G.; DeVree, B. T.; Zou, Y.; Kruse, A. C.; Chung, K. Y.; Kobilka, T. S.; Thian, F. S.; Chae, P. S.; Pardon, E.; Calinski, D.; Mathiesen, J. M.; Shah, S. T.; Lyons, J. A.; Caffrey, M.; Gellman, S. H.; Steyaert, J.; Skiniotis, G.; Weis, W. I.; Sunahara, R. K.; Kobilka, B. K. Crystal structure of the beta2 adrenergic receptor-Gs protein complex Nature 2011, 477, 549-555
19. Rasmussen, S. G.; Choi, H. J.; Rosenbaum, D. M.; Kobilka, T. S.; Thian, F. S.; Edwards, P. C.; Burghammer, M.; Ratnala, V. R.; Sanishvili, R.; Fischetti, R. F.; Schertler, G. F.; Weis, W. I.; Kobilka, B. K. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor Nature 2007, 450, 383-387
20. Leopoldo, M.; Berardi, F.; Colabufo, N. A.; De Giorgio, P.; Lacivita, E.; Perrone, R.; Tortorella, V. Structure-affinity relationship study on N -[4-(4-arylpiperazin-1-yl)butyl]arylcarboxamides as potent and selective dopamine D(3) receptor ligands J. Med. Chem. 2002, 45, 5727-5735
21. Newman, A. H.; Cao, J.; Bennett, C. J.; Robarge, M. J.; Freeman, R. A.; Luedtke, R. R. N -(4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl, butenyl and butynyl)arylcarboxamides as novel dopamine D(3) receptor antagonists Bioorg. Med. Chem. Lett. 2003, 13, 2179-2183
22. Campiani, G.; Butini, S.; Trotta, F.; Fattorusso, C.; Catalanotti, B.; Aiello, F.; Gemma, S.; Nacci, V.; Novellino, E.; Stark, J. A.; Cagnotto, A.; Fumagalli, E.; Carnovali, F.; Cervo, L.; Mennini, T. Synthesis and pharmacological evaluation of potent and highly selective D3 receptor ligands: inhibition of cocaine-seeking behavior and the role of dopamine D3/D2 receptors J. Med. Chem. 2003, 46, 3822-3839
23. Ballesteros, J.; Weinstein, H. Integrated methods for the construction of three-dimensional models of structure-function relations in G protein-coupled receptors Methods Neurosci. 1995, 25, 366-428
24. Simpson, M. M.; Ballesteros, J. A.; Chiappa, V.; Chen, J.; Suehiro, M.; Hartman, D. S.; Godel, T.; Snyder, L. A.; Sakmar, T. P.; Javitch, J. A. Dopamine D4/D2 receptor selectivity is determined by a divergent aromatic microdomain contained within the second, third, and seventh membrane-spanning segments Mol. Pharmacol. 1999, 56, 1116-1126
25. Abel, R.; Young, T.; Farid, R.; Berne, B. J.; Friesner, R. A. Role of the active-site solvent in the thermodynamics of factor Xa ligand binding J. Am. Chem. Soc. 2008, 130, 2817-2831
26. Higgs, C.; Beuming, T.; Sherman, W. Hydration Site Thermodynamics Explain SARs for Triazolylpurines Analogues Binding to the A2A Receptor ACS Med. Chem. Lett. 2010, 1, 160-164
27. Beuming, T.; Farid, R.; Sherman, W. High-energy water sites determine peptide binding affinity and specificity of PDZ domains Protein Sci. 2009, 18, 1609-1619
28. Morita, S.; Kitano, K.; Matsubara, J.; Ohtani, T.; Kawano, Y.; Otsubo, K.; Uchida, M. Practical application of the palladium-catalyzed amination in phenylpiperazine synthesis: an efficient synthesis of a metabolite of the antipsychotic agent aripiprazole Tetrahedron 1998, 54, 4811-4818
29. ten Hoeve, W.; Kruse, C. G.; Luteyn, J. M.; Thiecke, J. R. G.; Wynberg, H. Direct substitution of aromatic ethers by lithium amides. A new aromatic amination reaction J. Org. Chem. 1993, 58, 5101-5106
30. Mokrosz, J. L.; Paluchowska, M. H.; Chojnacka-Wojcik, E.; Filip, M.; Charakchieva-Minol, S.; Deren-Wesolek, A.; Mokrosz, M. J. Structure-activity relationship studies of central nervous system agents. 13. 4-[3-(Benzotriazol-1- yl)propyl]-1-(2-methoxyphenyl)piperazine, a new putative 5-HT1A receptor antagonist, and its analogs J. Med. Chem. 1994, 37, 2754-2760
31. Luedtke, R. R.; Freeman, R. A.; Boundy, V. A.; Martin, M. W.; Huang, Y.; Mach, R. H. Characterization of (125)I-IABN, a novel azabicyclononane benzamide selective for D2-like dopamine receptors Synapse 2000, 38, 438-449
32. Sherman, W.; Day, T.; Jacobson, M. P.; Friesner, R. A.; Farid, R. Novel procedure for modeling ligand/receptor induced fit effects J. Med. Chem. 2006, 49, 534-553
33. Taylor, M.; Grundt, P.; Griffin, S. A.; Newman, A. H.; Luedtke, R. R. Dopamine D3 receptor selective ligands with varying intrinsic efficacies at adenylyl cyclase inhibition and mitogenic signaling pathways Synapse 2010, 64, 251-266
34. Zaworski, P. G.; Alberts, G. L.; Pregenzer, J. F.; Im, W. B.; Slightom, J. L.; Gill, G. S. Efficient functional coupling of the human D3 dopamine receptor to G(o) subtype of G proteins in SH-SY5Y cells Br. J. Pharmacol. 1999, 128, 1181-1188
35. Lane, J. R.; Powney, B.; Wise, A.; Rees, S.; Milligan, G. G protein coupling and ligand selectivity of the D2L and D3 dopamine receptors J. Pharmacol. Exp. Ther. 2008, 325, 319-330
36. Gales, C.; Rebois, R. V.; Hogue, M.; Trieu, P.; Breit, A.; Hebert, T. E.; Bouvier, M. Real-time monitoring of receptor and G-protein interactions in living cells Nature Methods 2005, 2, 177-184
37. Urizar, E.; Yano, H.; Kolster, R.; Gales, C.; Lambert, N.; Javitch, J. A. CODA-RET reveals functional selectivity as a result of GPCR heteromerization Nature Chem. Biol. 2011, 7, 624-630
38. Cherezov, V.; Rosenbaum, D. M.; Hanson, M. A.; Rasmussen, S. G.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Kuhn, P.; Weis, W. I.; Kobilka, B. K.; Stevens, R. C. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor Science 2007, 318, 1258-1265
39. Rasmussen, S. G.; Choi, H. J.; Fung, J. J.; Pardon, E.; Casarosa, P.; Chae, P. S.; Devree, B. T.; Rosenbaum, D. M.; Thian, F. S.; Kobilka, T. S.; Schnapp, A.; Konetzki, I.; Sunahara, R. K.; Gellman, S. H.; Pautsch, A.; Steyaert, J.; Weis, W. I.; Kobilka, B. K. Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor Nature 2011, 469, 175-180
40. Warne, T.; Moukhametzianov, R.; Baker, J. G.; Nehme, R.; Edwards, P. C.; Leslie, A. G.; Schertler, G. F.; Tate, C. G. The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor Nature 2011, 469, 241-244
41. de Graaf, C.; Rognan, D. Selective structure-based virtual screening for full and partial agonists of the beta2 adrenergic receptor J. Med. Chem. 2008, 51, 4978-4985
42. Steinfeld, T.; Mammen, M.; Smith, J. A.; Wilson, R. D.; Jasper, J. R. A novel multivalent ligand that bridges the allosteric and orthosteric binding sites of the M2 muscarinic receptor Mol. Pharmacol. 2007, 72, 291-302
43. Liapakis, G.; Ballesteros, J. A.; Papachristou, S.; Chan, W. C.; Chen, X.; Javitch, J. A. The forgotten serine. A critical role for Ser-203(5.42) in ligand binding to and activation of the beta 2-adrenergic receptor J. Biol. Chem. 2000, 275, 37779-37788
44. Strader, C. D.; Candelore, M. R.; Hill, W. S.; Sigal, I. S.; Dixon, R. A. Identification of two serine residues involved in agonist activation of the beta-adrenergic receptor J. Biol. Chem. 1989, 264, 13572-13578
45. Sali, A.; Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints J. Mol. Biol. 1993, 234, 779-815
46. Kaminski, G. A.; Friesner, R. A.; Tirado-Rives, J.; Jorgensen, W. L. Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides J. Phys. Chem. B 2001, 105, 6474-6487
47. Guo, W.; Urizar, E.; Kralikova, M.; Mobarec, J. C.; Shi, L.; Filizola, M.; Javitch, J. A. Dopamine D2 receptors form higher order oligomers at physiological expression levels EMBO J. 2008, 27, 2293-2304