Arylpiperazines with serotonin-3 antagonist activity: A comparative molecular field analysis

Journal of Medicinal Chemistry

Volumn 41, Issue 12, 1998, Pages 2029-2039

  Morreale, Antonio ^a,b   Gálvez Ruano, Enrique ^b   Iriepa Canalda, Isabel ^b   Boyd, Donald B ^a  

^a INDIANA UNIVERSITY   (United States)

^b UNIVERSITY OF ALCALÁ   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

6 AMINO 5 CHLORO 1 ISOPROPYL 2 (4 METHYL 1 PIPERAZINYL)BENZIMIDAZOLE; ALOSETRON; AZASETRON; BEMESETRON; CILASETRON; GRANISETRON; ITASETRON; LERISETRON; N METHYLQUIPAZINE; ONDANSETRON; QUIPAZINE; RAMOSETRON; SEROTONIN 3 ANTAGONIST; SEROTONIN 3 RECEPTOR; TROPISETRON; UNCLASSIFIED DRUG; ZACOPRIDE; ZATOSETRON;

ARTICLE; DRUG CONFORMATION; DRUG RECEPTOR BINDING; MOLECULAR DYNAMICS; MOLECULAR MODEL; PREDICTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

LIGANDS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PIPERAZINES; RECEPTORS, SEROTONIN; RECEPTORS, SEROTONIN, 5-HT3; SEROTONIN ANTAGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032482376     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970745o     Document Type: Article

References (74)

1. 3 was given in this paper, but it has subsequently been revised; see: Gálvez-Ruano, E.; Iriepa, I.; Morreale, A. Natural Templates for the Nervous System Receptor Ligands. I. Competitive Antagonist Alkaloids at the Glycinergic, GABAergic, Cholinergic, and Serotonergic Receptors. Trends Heterocycl. Chem. 1997, 5, 135-144.
2. 3 was given in this paper, but it has subsequently been revised; see: Gálvez-Ruano, E.; Iriepa, I.; Morreale, A. Natural Templates for the Nervous System Receptor Ligands. I. Competitive Antagonist Alkaloids at the Glycinergic, GABAergic, Cholinergic, and Serotonergic Receptors. Trends Heterocycl. Chem. 1997, 5, 135-144.
3. 3 Receptors. Br. J. Pharmacol. 1988, 94, 397-412.
4. 3) Receptor Antagonists. 1. Indazole and Indolizine-3-carboxylic Acid Derivatives. J. Med. Chem. 1990, 33, 1924-1929.
5. Richardson, B. P.; Engel, G.; Donatsch, P.; Stadler, P. A. Identification of Serotonin M-Receptor Subtypes and Their Specific Blockade by a New Class of Drugs. Nature 1985, 316, 126-131.
6. 3 Antagonists. J. Pharm. Sci. 1995, 84, 101-106.
7. 3 Receptor Antagonist; Synthesis and Structure-Activity Relationships. J. Med. Chem. 1992, 35, 310-319.
8. Fozard, J. R. MDL 72222: A Potent and Highly Selective Antagonist at Neuronal 5-Hydroxytryptamine Receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 1984, 326, 36-44.
9. 3) Receptor Antagonists. III. Pharmacological Evaluations and Molecular Modeling Studies of Optically Active 4,5,6,7-Tetrahydro-1H-benzimidazole Derivatives. Chem. Pharm. Bull. 1996, 44, 1707-1716.
10. 3) Receptor Antagonists. Chem. Pharm. Bull. 1992, 40, 624-630.
11. 3 Receptor Antagonist Itasetron (DAU 6215) on (+)- N-Allylnormetazocina- Induced Dopamine Release in the Nucleus Accumbens and in the Corpus Striatum of the Rat: An In Vivo Microdialysia Study. J. Pharmacol. Exp. Ther. 1995, 275, 358- 367.
12. 3 Receptor Antagonists. Structure-Affinity Relationships of Novel 1,7-Annelated Indole Derivatives. 1. J. Med. Chem. 1993, 36, 3693-3699.
13. 3 Antagonist. J. Pharm. Pharmacol. 1988, 40, 301-302.
14. 3 Antagonists. Synthesis and Pharmacological Evaluation. J. Med. Chem. 1997, 40, 586-593.
15. 3 Receptor Antagonist) on the Pharmacokinetics of Haloperidol in Schizophrenic Patients. J. Clin. Pharmacol. 1995, 35, 202-207.
16. King, F. D.; Jones, J. B.; Sanger, G. J. 5-Hydroxytryptamine-3 Receptor Antagonists; CRC Press: Boca Raton, FL, 1994.
17. 3 Receptor Antagonists and a Definition of a Model for This Receptor Site. J. Med. Chem. 1990, 33, 1594-1600.
18. 3 Antagonists: Indol-3-ylspiro(azabicycloalkane-3,5′(4′H)-oxazoles). J. Med. Chem. 1992, 35, 1019-1031.
19. 3 Antagonist Recognition. In 5-Hydroxytryptamine-3 Receptor Antagonists; King, F. D., Jones, J. B., Sanger, G. J., Eds.; CRC Press: Boca Raton, FL, 1994; pp 45-66.
20. 3 Receptor Antagonists: Geometrical, Electronic and Lipophilic Features of the Pharmacophore and 3D-QSAR Study. Drug Des. Discovery 1994, 11, 205-222. See also: Dubost, J.-P. 2D and 3D Lipophilicity Parameters in QSAR. In Trends in QSAR and Molecular Modeling 92; Wermuth, C. G., Ed.; ESCOM: Leiden, 1993; pp 93-100.
21. 3 Receptor Antagonists: Geometrical, Electronic and Lipophilic Features of the Pharmacophore and 3D-QSAR Study. Drug Des. Discovery 1994, 11, 205-222. See also: Dubost, J.-P. 2D and 3D Lipophilicity Parameters in QSAR. In Trends in QSAR and Molecular Modeling 92; Wermuth, C. G., Ed.; ESCOM: Leiden, 1993; pp 93-100.
22. 3 Receptors. Quant. Struct.-Act. Relat. 1996, 15, 373-381.
23. 3 Receptor Binding. J. Med. Chem. 1997, 40, 3369-3380. These authors hypothesized that the first component, the aromatic ring, may play the role of only a spacer, whereas most other authors consider interactions of a delocalized π-electron system and the receptor important.
24. 3 Receptor Antagonists. J. Med. Chem. 1990, 33, 2715-2720.
25. Round, A.; Wallis, D. I. Further Studies on the Blockade of 5-HT Depolarizations of Rabbit Vagal Afferent and Sympathetic Ganglion Cells by MDL 72222 and Other Antagonists. Neuropharmacology 1987, 26, 39-48.
26. 3 Receptor Ligands and Substance P. J. Neurochem. 1993, 60, 2059-2067.
27. 3 Serotonin Receptors: Results of a Structure-Affinity Study. Eur. J. Pharmacol. 1989, 168, 387-392.
28. 3) Antagonist Series. In Progress in Drug Research; Jucker, E., Ed.; Birkhäuser Verlag: Basel, 1993; Vol. 41, pp 313-357.
29. 3) Antagonist Series. In Progress in Drug Research; Jucker, E., Ed.; Birkhäuser Verlag: Basel, 1993; Vol. 41, pp 313-357.
30. 3 Serotonin Sites. Med. Chem. Res. 1993, 3, 44-51.
31. 4 Agonist Properties. J. Med. Chem. 1994, 37, 1320-1325.
32. 3 Receptor Antagonists Based on the Arylpiperazine Skeleton: Synthesis, Structure, Biological Activity, and Comparative Molecular Field Analysis Studies. J. Med. Chem. 1995, 38, 2692- 2704.
33. 3 Receptor Sites. Med. Chem. Res. 1996, 6, 81-101.
34. 3 Serotonin Receptors, J. Med. Chem. 1996, 39, 4017-4026.
35. Greco, G.; Novellino, E.; Martin, Y. C. Approaches to Three- Dimensional Quantitative Structure-Activity Relationships. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; Wiley-VCH: New York, 1997; Vol. 11, pp 127-182.
36. Oprea, T. I.; Waller, C. L. Theoretical and Practical Aspects of Three-Dimensional Quantitative Structure-Activity Relationships. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; Wiley-VCH: New York, 1997; Vol. 11, pp 183-240.
37. 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.
38. Cramer, R. D., III; DePriest, S. A.; Patterson, D. E.; Hecht, P. The Developing Practice of Comparative Molecular Field Analysis. In 3D-QSAR in Drug Design: Theory, Methods and Applications; Kubinyi, H., Ed.; ESCOM: Leiden, 1993; pp 443-485.
39. Martin, Y. C.; Kim, K. H.; Lin, C. T. Comparative Molecular Field Analysis: CoMFA. In Advances in Quantitative Structure- Property Relationships; Charton, M., Ed.; JAI Press: Greenwich, CT, 1996; Vol. 1, pp 1-52.
40. 1B Receptors. Eur. J. Pharmacol. 1993, 244, 77-87.
41. 1B Receptors. Eur. J. Pharmacol. 1993, 244, 77-87.
42. 1B Receptors. Eur. J. Pharmacol. 1993, 244, 77-87.
43. 3 Receptors Mediate Rapid Response in Cultured Hippocampus and a Clonal Cell Line. Neuron 1988, 1, 615-621.
44. 3H]-Granisetron Binding. J. Neurochem. 1996, 67, 407-412.
45. 3 Receptor Antagonists. Insight in the Interaction with the Receptor. Bioorg. Med. Chem. 1996, 4, 1255-1269.
46. Codding, P. W.; James, M. N. G. The Crystal and Molecular Structure of a Potent Neuromuscular Blocking Agent: d- Tubocurarine Dichloride Pentahydrate. Acta Crystallogr., Sect. B 1973, 29, 935-942.
47. SYBYL, version 6.1; Tripos Associates, 1699 S. Hanley Rd, Suite 303, St. Louis, MO 63144.
48. Clark, M.; Cramer, R. D., III; Van Opdenbosch, N. Validation of the General Purpose Tripos 5.2 Force Field. J. Comput. Chem. 1989, 10, 982-1012.
49. Leach, A. R. A Survey of Methods for Searching the Conformational Space of Small and Medium-Sized Molecules. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; VCH Publishers: New York, 1991; Vol. 2, pp 1-55.
50. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. AM1: A New General Purpose Quantum Mechanical Molecular Model. J. Am. Chem. Soc. 1985, 107, 3902-3909. See also: Stewart, J. J. P. Semiempirical Molecular Orbital Methods. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; VCH Publishers: New York, 1990; Vol. 1, pp 45- 81.
51. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. AM1: A New General Purpose Quantum Mechanical Molecular Model. J. Am. Chem. Soc. 1985, 107, 3902-3909. See also: Stewart, J. J. P. Semiempirical Molecular Orbital Methods. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; VCH Publishers: New York, 1990; Vol. 1, pp 45- 81.
52. Stewart, J. J. P. MOPAC: A General Molecular Orbital Package. Quant. Chem. Prog. Exch. Bull. 1993, 13, 40-43. MOPAC version 7.0 (Fujitsu Ltd.) is available as Program 455 from QCPE, Indiana University, Bloomington, IN 47405.
53. Quanta96; Molecular Simulations, Inc., 9685 Scranton Rd, San Diego, CA 92121.
54. Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. CHARMM: A Program for Macromolecular Energy, Minimization and Dynamics Calculations. J. Comput. Chem. 1983, 4, 187-217.
55. Momany, F. A.; Rone, R. Validation of the General Purpose QUANTA3.2/CHARMm Force Field. J. Comput. Chem. 1992, 7, 888-900.
56. Schlick, T. Optimization Methods in Computational Chemistry. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; VCH Publishers: New York, 1992; Vol. 3, pp 1-71.
57. Motoc, I.; Dammkoehler, R. A.; Mayer, D.; Labanowski, J. Three- Dimensional Quantitative Structure-Activity Relationships. I. General Approach to the Pharmacophore Model Validation. Quant. Struct.-Act. Relat. 1986, 5, 99-105. Labanowski, J.; Motoc, I.; Naylor, C. B.; Mayer, D.; Dammkoehler, R. A. Three- Dimensional Quantitative Structure-Activity Relationships. 2. Conformational Mimicry and Topographical Similarity of Flexible Molecules. Quant. Struct.-Act. Relat. 1986, 5, 138-152.
58. Motoc, I.; Dammkoehler, R. A.; Mayer, D.; Labanowski, J. Three- Dimensional Quantitative Structure-Activity Relationships. I. General Approach to the Pharmacophore Model Validation. Quant. Struct.-Act. Relat. 1986, 5, 99-105. Labanowski, J.; Motoc, I.; Naylor, C. B.; Mayer, D.; Dammkoehler, R. A. Three- Dimensional Quantitative Structure-Activity Relationships. 2. Conformational Mimicry and Topographical Similarity of Flexible Molecules. Quant. Struct.-Act. Relat. 1986, 5, 138-152.
59. Lin, H.-S.; Rampersaud, A. A.; Zimmerman, K.; Steinberg, M. I.; Boyd, D. B. Nonpeptide Angiotensin II Receptor Antagonists: Synthetic and Computational Chemistry of N-[[4-[2-(2H- Tetrazol-5-yl)-l-cycloalken-l-yl]phenyl]methyl]imidazole Derivatives and Their In Vitro Activity. J. Med. Chem. 1992, 35, 2658- 2667. Boyd, D. B.; Palkowitz, A. D.; Thrasher, K. J.; Hauser, K. L.; Whitesitt, C. A.; Reel, J. K.; Simon, R. L.; Pfeifer, W.; Lifer, S. L.; Takeuchi, K.; Vasudevan, V.; Kossoy, A. D.; Deeter, J. B.; Steinberg, M. I.; Zimmerman, K. M.; Wiest, S. A.; Marshall, W. S. Molecular Modeling and Quantitative Structure-Activity Relationship Studies in Pursuit of Highly Potent Substituted Octanoamide Angiotensin II Receptor Antagonists. In Computer- Aided Molecular Design: Applications in Agrochemicals, Materials, and Pharmaceuticals; ACS Symp. Series 589; Reynolds, C. H., Holloway, M. K., Cox, H. K., Eds.; American Chemical Society: Washington, DC, 1995; pp 14-35.
60. Lin, H.-S.; Rampersaud, A. A.; Zimmerman, K.; Steinberg, M. I.; Boyd, D. B. Nonpeptide Angiotensin II Receptor Antagonists: Synthetic and Computational Chemistry of N-[[4-[2-(2H- Tetrazol-5-yl)-l-cycloalken-l-yl]phenyl]methyl]imidazole Derivatives and Their In Vitro Activity. J. Med. Chem. 1992, 35, 2658- 2667. Boyd, D. B.; Palkowitz, A. D.; Thrasher, K. J.; Hauser, K. L.; Whitesitt, C. A.; Reel, J. K.; Simon, R. L.; Pfeifer, W.; Lifer, S. L.; Takeuchi, K.; Vasudevan, V.; Kossoy, A. D.; Deeter, J. B.; Steinberg, M. I.; Zimmerman, K. M.; Wiest, S. A.; Marshall, W. S. Molecular Modeling and Quantitative Structure-Activity Relationship Studies in Pursuit of Highly Potent Substituted Octanoamide Angiotensin II Receptor Antagonists. In Computer- Aided Molecular Design: Applications in Agrochemicals, Materials, and Pharmaceuticals; ACS Symp. Series 589; Reynolds, C. H., Holloway, M. K., Cox, H. K., Eds.; American Chemical Society: Washington, DC, 1995; pp 14-35.
61. Cramer, C. J.; Truhlar, D. G. Continuum Solvation Models: Classical and Quantum Mechanical Implementations, In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; VCH Publishers: New York, 1995; Vol. 6, pp 1-72.
62. Hehre, W. J.; Burke, L. D.; Shusterman, A. J. A Spartan Tutorial; Wavefunction, Inc.: Irvine, CA, 1993. Spartan version 4.1.1 was used.
63. Alignment was performed with optimized structures in SYBYL, and charges were obtained with the Gasteiger-Hückel method. Once the alignment was performed in this way (models 1 and 4), charges were computed on these geometries with the other theoretical methods (models 2, 3, 5, and 6).
64. Williams, D. E. Net Atomic Charge and Multipole Models for the Ab Initio Molecular Electric Potential. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; VCH Publishers: New York, 1991; Vol. 2, pp 219-271. See also: Francl, M. M.; Chirlian, L. E. The Plusses and Minuses of Mapping Atomic Charges to Electrostatic Potentials. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; Wiley-VCH: New York, in press.
65. Williams, D. E. Net Atomic Charge and Multipole Models for the Ab Initio Molecular Electric Potential. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; VCH Publishers: New York, 1991; Vol. 2, pp 219-271. See also: Francl, M. M.; Chirlian, L. E. The Plusses and Minuses of Mapping Atomic Charges to Electrostatic Potentials. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; Wiley-VCH: New York, in press.
66. Kroemer, R. T.; Hecht, P.; Liedl, K. R. Different Electrostatic Descriptors in Comparative Molecular Field Analysis: A Comparison of Molecular Electrostatic and Coulomb Potentials. J. Comput. Chem. 1996, 17, 1296-1308.
67. Geladi, P.; Kowalski, B. R. Partial Least-Squares Regression: A Tutorial. Anal. Chim. Acta 1986, 185, 1-17.
68. Höskuldsson, A. PLS Regression Methods. J. Chemomet. 1988, 2, 211-228.
69. Ståhle, L.; Wold, S. Multivariate Data Analysis and Experimental Design in Biomedical Research. In Progress in Medicinal Chemistry; Ellis, G. P., West, G. B., Eds.; Elsevier Science Publishers: Amsterdam, 1988; Vol. 25, pp 291-338.
70. Argarwal, A.; Pearson, P. P.; Taylor, E. W.; Li, H. B.; Dahlgren, T.; Herslöf, M.; Yang, Y.; Lambert, G.; Nelson, D. L.; Regan, J. W.; Martin, A. R. Three-Dimensional Quantitative Structure- Activity Relationships of 5-HT Receptor Binding Data for Tetrahydropyridinylindole Derivatives: A Comparison of the Hansch and CoMFA Methods. J. Med. Chem. 1993, 36, 4006- 4014.
71. 2-Guided Region Selection for Comparative Molecular Field Analysis: A Simple Method To Achieve Consistent Results. J. Med. Chem. 1995, 38, 1060-1066.
72. 3 Receptors. Synthesis and Biological Evaluation of Piperazinylquinoxaline Derivatives. J. Med. Chem. 1993, 36, 2745- 2750.
73. 3 Receptor Binding Site by Arylpiperazine Derivatives. J. Med. Chem. 1998, 41, 728-741.
74. 3 Receptor Binding Site by Arylpiperazine Derivatives. J. Med. Chem. 1998, 41, 728-741.