Structure-selectivity investigations of D2-like receptor ligands by CoMFA and CoMSIA guiding the discovery of D3 selective PET radioligands

Journal of Medicinal Chemistry

Volumn 50, Issue 3, 2007, Pages 489-500

  Salama, Ismail ^a   Hocke, Carsten ^b   Utz, Wolfgang ^a   Prante, Olaf ^b   Boeckler, Frank ^a   Hübner, Harald ^a   Kuwert, Torsten ^b   Gmeiner, Peter ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b Department of Nuclear Medicine ^*  (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ARIPIPRAZOLE; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; FLUORINE 18; HALOPERIDOL; N [4 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]BUTYL] 4 (6 FLUOROPYRIDIN 2 YL)BENZAMIDE; N [4 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]BUTYL] 4 (6 FLUOROPYRIDIN 2 YL)BENZAMIDE F18; N [4 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]BUTYL] 4 (6 FLUOROPYRIDIN 3 YL)BENZAMIDE; N [4 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]BUTYL] 4 (6 FLUOROPYRIDIN 3 YL)BENZAMIDE F18; TRACER; UNCLASSIFIED DRUG;

ARTICLE; COMPARATIVE MOLECULAR FIELD ANALYSIS; COMPARATIVE MOLECULAR SIMILARITY INDICES ANALYSIS; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; FLUORINATION; LIGAND BINDING; POSITRON EMISSION TOMOGRAPHY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BENZAMIDES; FLUORINE RADIOISOTOPES; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PIPERAZINES; POSITRON-EMISSION TOMOGRAPHY; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RADIOLIGAND ASSAY; RADIOPHARMACEUTICALS; RECEPTORS, DOPAMINE D2; RECEPTORS, DOPAMINE D3; SWINE;

EID: 33846930565     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0611152     Document Type: Article

References (72)

1. Massoud, T. F.; Gambhir, S. S. Molecular imaging in living subjects: Seeing fundamental biological processes in a new light. Genes Dev. 2003, 17, 545-580.
2. Lemaire, C.; Damhaut, P.; Plenevaux, A.; Comar, D. Enantioselective synthesis of 6-[fluorine-18]-fluoro-L-dopa from no-carrier-added fluorine-18-fluoride. J. Nucl. Med. 1994, 35, 1996-2002.
3. Langer, O.; Nagren, K.; Dollé, F.; Lundkvist, C.; Sandell, J.; Swahn, C.-G.; Vaufrey, F.; Crouzel, C.; Maziere, B.; Halldin, C. Precursor synthesis and radiolabelling of the dopamine D-2 receptor ligand [C-11]raclopride from [C-11]methyl triflate. J. Labelled Compd. Radiopharm. 1999, 42, 1183-1193.
4. 18F-fallypride in normal volunteers: Blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors. Synapse 2002, 46, 170-188.
5. 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.
6. Langer, O.; Gulyas, B.; Sandell, J.; Laszlovszky, I.; Kiss, B.; Domany, G.; Acs, T.; Farde, L.; Halldin, C. Radiochemical labelling of the dopamine D-3 receptor ligand RGH-1756. J. Labelled Compd. Radiopharm. 2000, 43, 1069-1074.
7. 11C]RGH-1756 the monkey brain. Neurochem. Int. 2004, 45, 609-617.
8. De Vries, E. F.; Kortekaas, R.; van Waarde, A.; Dijkstra, D.; Elsinga, P. H.; Vaalburg, W. Synthesis and evaluation of dopamine D3 receptor antagonist 11C-GR218231 as PET tracer for P-glycoprotein. J. Nucl. Med. 2005, 46, 1384-1392.
9. Seeman, P.; Wilson, A.; Gmeiner, P.; Kapur, S. Dopamine D2 and D3 receptors in human putamen, caudate nucleus, and globus pallidus. Synapse 2006, 60, 205-211.
10. Hocke, C.; Prante, O.; Löber, S.; Hübner, H.; Gmeiner, P.; Kuwert, T. Synthesis and evaluation of 18F-labeled dopamine D3 receptor ligands as potential PET imaging agents. Bioorg. Med. Chem. Lett. 2005, 15, 4819-4823.
11. 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 elozapine. J. Med. Chem. 2001, 44, 1151-1157.
12. Boeckler, F.; Ohnmacht, U.; Lehmann, T.; Utz, W.; Hübner, 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.
13. Salama, I.; Schlotter, K.; Utz, W.; Hübner, H.; Gmeiner, P.; Boeckler, F. CoMFA and CoMSIA investigations of dopamine D3 receptor ligands leading to the prediction, synthesis, and evaluation of rigidized FAUC 365 analogues. Bimtrg. Med. Chem. 2006, 14, 5898-5912.
14. Cramer, R. D., III; Patterson, D. E.; Bunce, J. D. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 1988, 110, 5959- 5967.
15. Kubinyi, H., Ed, 3D-QSAR in Drug Design. Theory, Methods and Applications; ESCOM: Leiden, The Netherlands, 1993.
16. Kubinyi, H.; Folkers, G.; Martin, Y. C., Eds. 3D-QSAR in Drug Design. Volume 2. Ligand-Protein Interactions and Molecular Similarity; Kluwer/ESCOM: Dordrecht, The Netherlands, 1997.
17. Kubinyi, H.; Folkers, G.; Martin, Y. C., Eds, 3D-QSAR in Drug Design. Volume 3. Recent Advances; Kluwer/ ESCOM: Dordrecht, The Netherlands, 1998.
18. Klebe, G.; Abraham, U.; Mietzner, T. Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J. Med. Chem. 1994, 37, 4130-4146.
19. Böhm, M.; Stürzebecher, J.; Klebe, G. Three-dimensional quantitative structure-activity relationship analyses using comparative molecular field analysis and comparative molecular similarity indices analysis to elucidate selectivity differences of inhibitors binding to trypsin, thrombin, and factor Xa. J. Med. Chem. 1999, 42, 458-477.
20. Baskin, I. I.; Tikhonova, I. G.; Palyulin, V. A.; Zefirov, N. S. Selectivity fields: Comparative molecular field analysis (CoMFA) of the glycine/NMDA and AMPA receptors. J. Med. Chem. 2003, 46, 4063-4069.
21. Yang, G.-F.; Lu, H.-T.; Xiong, Y.; Zhan, C.-G. Understanding the structure-activity and structure-selectivity correlation of cyclic guanine derivatives as phosphodiesterase-5 inhibitors by molecular docking, CoMFA and CoMSIA analyses. Bioorg. Med. Chem. 2006, 14, 1462-1473.
22. Melville, J. L.; Lovelock, K. R. J.; Wilson, C.; Allbutt, B.; Burke, E. K.; Lygo, B.; Hirst, J. D. Exploring phase-transfer catalysis with molecular dynamics and 3D/4D quantitative structure selectivity relationships. J. Chem. Inf. Model. 2005, 45, 971-981.
23. Catto, M.; Nicolotti, O.; Leonetti, F.; Carotti, A.; Favia, A. D.; SotoOtero, R.; Mendez-Alvarez, E.; Carotti, A. Structural insights into monoamine oxidase inhibitory potency and selectivity of 7-substituted coumarins from ligand- and target-based approaches. J. Med. Chem. 2006, 49, 4912-4925.
24. 3 receptors. Med. Chem. Res. 1999, 9, 355-373.
25. Wilcox, R. E.; Tseng, T.; Brusniak, M. Y.; Ginsburg, B.; Pearlman, R. S.; Teeter, M.; DuRand, C.; Starr, S.; Neve, K. A. CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine receptors. J. Med. Chem. 1998, 41, 4385-4399.
26. Wilcox, R. E.; Huang, W. H.; Brusniak, M. Y.; Wilcox, D. M.; Pearlman, R. S.; Teeter, M. M.; DuRand, C. J.; Wiens, B. L.; Neve, K. A. CoMFA-based prediction of agonist affinities at recombinant wild type versus serine to alanine point mutated D2 dopamine receptors. J. Med. Chem. 2000, 43, 3005-3019.
27. Ravina, E.; Negreira, J.; Cid, J.; Masaguer, C. F.; Rosa, E.; Rivas, M. E.; Fontenla, J. A.; Loza, M. I.; Tristan, H.; Cadavid, M. I.; Sanz, F.; Lozoya, E.; Carotti, A.; Carrieri, A. Conformationally constrained butyrophenones with mixed dopaminergic (D(2)) and serotoninergic (5-HT(2A), 5- HT(2Q) affinities: Synthesis, pharmacology, 3D-QSAR, and molecular modeling of (aminoalkyl)benzo- and thienocycloalkanones as putative atypical antipsychotics. J. Med. Chem. 1999, 42, 2774-2797.
28. Norinder, U.; Hogberg, T. A quantitative structure-activity relationship for some dopamine D2 antagonists of benzamide type. Acta Pharm. Nord. 1992, 4, 73-78.
29. McGaughey, G. B.; Mewshaw, R. E. Application of comparative molecular field analysis to dopamine D2 partial agonists. Bioorg. Med. Chem. 1999, 7, 2453-2456.
30. Homan, E. J.; Tulp, M. T.; Nilsson, J. E.; Wikström, H. V.; Grol, C. J. C5-substituted derivatives of 5-OMe-BPAT: Synthesis and interactions with dopamine D2 and serotonin 5-HT1A receptors. Bioorg. Med. Chem. 1999, 7, 2541-2548.
31. Hackling, A.; Ghosh, R.; Perachon, S.; Mann, A.; Höltje, H. D.; Wermuth, C. G.; Schwartz, J. C.; Sippl, W.; Sokoloff, P.; Stark, H. N-(ω-(4-(2-Methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as dopamine D2 and D3 receptor ligands. J. Med. Chem. 2003, 46, 3883-3899.
32. De Faillis, T.; El Tayar, N.; Carrupt, P. A.; Testa, B.; Van de Waterbeemd, H. Quantitative structure-affinity relationships of dopamine D2 receptor antagonists: A comparison between orthopramides and 6-methoxysalicylamides. Helv. Chim. Acta 1991, 74, 241-254.
33. Cha, M. Y.; Lee, I. Y.; Cha, J. H.; Choi, K. I.; Cho, Y. S.; Koh, H. Y.; Pae, A. N. QSAR studies on piperazinylalkylisoxazole analogues selectively acting on dopamine D3 receptor by HQSAR and CoMFA. Bioorg. Med. Chem. 2003, 11, 1293-1298.
34. Boström, J.; Gundertofte, K.; Liljeforsa, T. A pharmacophore model for dopamine D4 receptor antagonists. J. Comput.-Aided Mol. Des. 2000, 14, 769-786.
35. Boström, J.; Böhm, M.; Gundertofte, K.; Klebe, G. A 3D QSAR study on a set of dopamine D4 receptor antagonists. J. Chem. Inf. Comput. Sci. 2003, 43, 1020-1027.
36. Löber, S.; Hübner, H.; Gmeiner, P. Azaindole derivatives with high affinity for the dopamine D4 receptor: Synthesis, ligand binding studies, and comparison of molecular electrostatic potential maps. Bioorg. Med. Chem. Lett. 1999, 9, 97-102.
37. 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.
38. 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.
39. Bettinetti, L.; Schlotter, K.; Hübner, H.; Gmeiner, P. Interactive SAR studies: Rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists. J. Med. Chem. 2002, 45, 4594-4597.
40. Bettinetti, L.; Löber, S.; Hübner, H.; Gmeiner, P. Parallel synthesis and biological screening of dopamine receptor ligands taking advantage of a click chemistry based BAL linker. J. Comb. Chem. 2005, 7, 309-316.
41. Loaiza, P. R.; Löber, S.; Hübner, H.; Gmeiner, P. Click chemistry on solid phase: Parallel synthesis of N-benzyltriazole carboxamides as super-potent G-protein coupled receptor ligands. J. Comb. Chem. 2006, 8, 252-261.
42. Löber, S.; Hübner, H.; Gmeiner, P. Synthesis and biological investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype. Bioorg. Med. Chem. Lett. 2006, 16, 2955-2959.
43. Koob, G. F.; Caine, S. B. Cocaine addiction therapy - are we partially there? Nat. Med. 1999, 5, 993-995.
44. Chavez-Eng, C. M.; Constanzer, M. L.; Matuszewski, B. K. Picogram determination of a novel dopamine D4 receptor antagonist in human plasma and urine by liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry. J. Chromatogr., B. 1997, 691, 77-85.
45. ASP V3.22, Oxford Molecular, Ltd.: The Medawar Centre, Oxford Science Park, Sandford-on-Thames, Oxford OX4 4GA, U.K., 1998.
46. TSAR V3.2, Oxford Molecular, Ltd.: The Medawar Centre, Oxford Science Park, Sandford-on-Thames, Oxford OX44GA, U.K., 1998.
47. Wang, R.; Gao, Y.; Liu, L.; Lai, L. All-orientation search and all-placement search in comparative molecular field analysis. J. Mol. Model. 1998, 4, 276-283.
48. Thibaut, U.; Folkers, G.; Klebe, G.; Kubinyi, H.; Merz, A.; Rognan, D. Recommendations to CoMFA studies and 3D QSAR publications. In 3D QSAR in Drug Design. Theory, Methods and Applications; Kubinyi, H., Ed.; ESCOM: Leiden, The Netherlands, 1993; pp 711-716.
49. Murray, P. J.; Harrison, L. A.; Johnson, M. R.; Robertson, G. M.; Scopes, D. I.; Bull, D. R.; Graham, E.; Hayes, A. G.; Kilpatrick, G. J. A novel series of arylpiperazines with high affinity and selectivity for the dopamine D3 receptor. Bioorg. Med. Chem. Lett. 1995, 5, 219-222.
50. Yuan, Y.; Chen, C.; Brodbeck, R.; Primus, R.; Braun, J.; Wasley, J. W. F.; Thurkauf, A. NGB 2904 and NGB 2849: Two highly selective dopamine D3 receptor antagonists. Bioorg. Med. Chem. Lett. 1998, 8, 2718-2718.
51. 222 - a comparative study. J. Labelled Compd. Radiopharm. 1999, 42, 975-985.
52. 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.
53. 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.
54. 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.
55. 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.
56. 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.
57. Sybyl 6.9, Tripos, Inc.: 1699 South Hanley Road, St. Louis, Missouri, 63144, 2002.
58. Clark, M.; Cramer, R.-D.; Van Opdenbosch, N. Validation of the general purpose Tripos 5.2 force field. J. Comput. Chem. 1989, 10, 982-1012.
59. Gasteiger, J.; Marsili, M. Iterative partial equalization of orbital electronegativity: A rapid access to atomic charges. Tetrahedron 1980, 36, 3219-3222.
60. Hinze, J.; Jaffe, H. H. Electronegativity. I. Orbital electronegativity of neutral atoms. J. Am. Chem. Soc. 1962, 84, 540-546.
61. Stewart, J. J. MOPAC: A semiempirical molecular orbital program. J. Comput.-Aided Mol. Design 1990, 4, 1-105.
62. Stewart, J. J. P.; Frank, J. MOPAC; Seiler Bokstav Research Laboratory: United States Air Force Academy, CO 80840, 1990.
63. Beck, B.; Clark, T.; Glen, R. C. A detailed study of VESPA electrostatic potential-derived atomic charges. J. Mol. Model. 1995, 1, 176-187.
64. Clark, T.; Alex, A.; Beck, B.; Chandrasekar, J.; Gedeck, P.; Horn, A.; Huttern, M.; Martin, B.; Rauhut, G.; Sauer, W.; Schindler, T.; Steinke, T. VAMP 7.0 Program Package; Oxford Molecular Plc.: Oxford, 1998.
65. 2-guided region selection for comparative molecular field analysis: A simple method to achieve consistent results. J. Med. Chem. 1995, 38, 1060-1066.
66. Viswanadhan, V. N.; Ghose, A. K.; Revankar, G. R.; Robins, R. K. Atomic physichochemical parameters for three dimensional structure directed quantitative structure-activity relationships. 4. Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibiotics. J. Chem. Inf. Comput. Sci. 1989, 29, 163-172.
67. Klebe, G. The use of composite crystal-field environments in molecular recognition and the de novo design of protein ligands. J. Mol. Biol. 1994, 237, 212-235.
68. Wold, S. Validation of QSAR's. Quant. Struct.-Acr. Relat. 1991, 10, 191-193.
69. Baroni, M.; Clementi, S.; Cruciani, G.; Costantino, G.; Riganelli, D.; Oberrauch, E. Predictive ability of regression models. Part II. Selection of the best predictive PLS model. J. Chemom. 1992, 6, 347-356.
70. Gong, Y.; Pauls, H. W. A convenient synthesis of heteroaryl benzoic acids via suzuki reaction. Synlett 2000, 6, 829-831.
71. 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.
72. 50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.