Quasi-atomistic receptor surrogates for the 5-HT(2A) receptor: A 3D-QSAR study on hallucinogenic substances

Quantitative Structure-Activity Relationships

Volumn 18, Issue 6, 1999, Pages 548-560

  Schulze Alexandru, Meike ^a   Kovar, Karl Artur ^a   Vedani, Angelo ^b  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b Biographics Laboratory 3R   (Switzerland)

Author keywords

3D QSAR; 5 HT(2A) receptor agonists; Designer drugs; Hallucinogens; Quasi atomistic receptor modeling; Software Quasar

Indexed keywords

BINDING ENERGY; COMPUTATIONAL CHEMISTRY; FLIP FLOP CIRCUITS; GALAXIES;

3D-QSAR; 5-HT(2A) RECEPTOR AGONIST; ATOMISTICS; BIOLOGICAL TARGETS; DESIGNER DRUGS; HALLUCINOGEN; QSAR STUDIES; QUASI-ATOMISTIC RECEPTOR MODELING; RECEPTOR MODELING; SOFTWARE QUASAR;

GENETIC ALGORITHMS;

PSYCHEDELIC AGENT; SEROTONIN 2A RECEPTOR;

ARTICLE; BINDING AFFINITY; COMPUTER MODEL; COMPUTER PROGRAM; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; SIMULATION;

EID: 0033394430     PISSN: 09318771     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-3838(199912)18:6<548::AID-QSAR548>3.0.CO;2-B     Document Type: Article

References (62)

1. Glennon, R.A., Investigations with serotonin and hallucinogenic agents, http://wwvt:phc.vcu.edu/rag/serotonin/index.htm, 1-15 (1998).
2. Nichols, D.E., Structure-activity relationships of phenethylamine hallucinogens, J. Pharm. Sci. 70 (8), 839-849 (1981).
3. Glennon, R.A. and Gessner, P.K., Serotonin receptor binding affinities of tryptamine analogues, J. Med. Chem. 22 (4), 428-432 (1979).
4. Nichols, D.E., Studies of the relationship between molecular structure and hallucinogenic activity. Pharmacol. Biochem. Behav. 24 (2), 335-340 (1986).
5. Oberlender, R., Ramachandran, P.V., Johnson, M.P., Huang, X. and Nichols, D.E., Effect of a chiral 4-alkyl substituent in hallucinogenic amphetamines, J. Med. Chem. 38 (18), 3593-3601 (1995).
6. Huang, X., Marona-Lewicka, D., Pfaff, R.C. and Nichols, D.E., Drug discrimination and receptor binding studies of N-isopropyl lysergamide derivatives, Pharmacol. Biochem. Behav. 41 (3), 667-673 (1994).
7. Nichols, D.E. and Glennon, R.A., In: Hallucinogens: Neurochemical, Behavioral and Clinical Perspectives, edited by B.L. Jacobs, Raven Press, New York, 95-141 (1984).
8. Shulgin, A.T. In: Burger's Medicinal Chemistry, part III 4th edition, edited by M.E. Wolff, New York: Wiley, 1109-1137 (1981).
9. 2 receptor subtypes, Mol. Pharmacol. 38 (5), 594-598 (1990).
10. 2 receptor, Mol. Pharmacol. 38 (5), 604-609 (1990).
11. 3H] DOB: a specific agonist radioligand for 5-HT serotonin receptors, Ew. J. Pharmacol. 117 (1), 145-146 (1985).
12. 2 serotonin receptors: examination of a hydrophobic binding region, J. Med. Chem. 33 (10), 2777-2784 (1990).
13. 2 receptors, Mol. Pharmacol. 31 (2), 194-199 (1987).
14. Westkaemper, R.B. and Glennon, R.A., Approaches to molecular modeling studies and specific application to serotonin ligands and receptors, Pharmacol. Biochem. Behav. 40 (4), 1019-1031 (1991).
15. Hibert, M.F., Trumpp-Kallmeyer, S., Bruinvels, A. and Hoflack, J., Three-dimensional models of neurotransmitter G-binding protein-coupled receptors, Mol. Pharmacol. 40 (1), 8-15 (1991).
16. Trumpp-Kallmeyer, S., Hoflack, J., Bruinvels, A. and Hibert, M., Modeling of G-protein-coupled receptors: application to dopamine, adrenaline, serotonin, acetylcholine, and mammalian opsin receptors, J. Med. Chem. 35 (19), 3448-3462 (1992).
17. Pardo, L., Ballesteros, J.A., Osman, R. and Weinstein, H., On the use of the transmembrane domain of bacteriorhodopsin as a template for modeling the three-dimensional structure of guanine nucleotide-binding regulatory protein-coupled receptors, Proc. Natl. Acad. Sci. USA 89 (9), 4009-4012 (1992).
18. 2a receptor model, Arch. Pharm. (Weinheim) 328 (7-8), 597-584 (1995).
19. 2 receptor: a mechanistic hypothesis from molecular dynamics simulations of the three-dimensional model of the receptor complexed to ligands, J. Med. Chem. 36 (7), 934-938 (1993).
20. Clare, B.W., Structure-activity correlations for psychotomimetics. 1. Phenylalkylamines: electronic, volume, and hydrophobicity parameters, J. Med. Chem. 33 (2), 687-702 (1990).
21. Clare, B.W., The frontier orbital phase angles: novel QSAR descriptors for benzene derivatives, applied to phenylalkylamine hallucinogens, J. Med. Chem. 41 (20), 3845-3856 (1998).
22. Gomez-Jeria, J.S. and Morales-Lagos, D.R., Quantum chemical approach to the relationship between molecular structure and serotonin receptor binding affinity, J. Pharm. Sci. 73 (12), 1725-1728 (1984).
23. Gupta, S.P., Singh, P. and Bindal, M.C., QSAR studies on hallucinogens, Chem. Rev. 83, 633-649 (1983).
24. Henderson, R., Baldwin, J.M., Ceska, T.A., Zemlin, F., Beckmann, E. and Downing, K.H., Model for the structure of bacteriorhodopsin based on high-resolution electron cryomicroscopy, J. Mol. Biol. 213 (4), 899-929 (1990).
25. Beuerle, G., Kovar, K.-A. and Schulze-Alexandru, M., Three-dimensional quantitative structure-activity relationships of hallucinogenic phenylalkanamine and tryptamine derivatives: studies using comparative molecular field analysis (CoMFA), Quant. Struct.-Act. Relat. 16, 447-458 (1997).
26. Nichols, D.E., Differences between the mechanism of action of MDMA, MBDB and the classic hallucinogens. Identification of a new therapeutic class: Entactogens, J. Psvchoact. Drugs 18, 305-313 (1986).
27. Vedani, A., Dobler, M. and Zbinden, P., Quasi-atomistic receptor surface models: A bridge between 3-D QSAR and receptor modeling, J. Am. Chem. Soc. 120, 4471-4477 (1998).
28. 2 serotonin receptors: evidence for a lack of selectivity, J. Med. Chem. 35 (4), 734-740 (1992).
29. 2 agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane, J. Med. Chem. 30 (5), 930-932 (1987).
30. 2 binding properties of derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane (2,5-DMA), Eur. J. Pharmacol. 102 (1), 23-29 (1984).
31. 2 binding characteristics of 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane analogues, J. Med. Chem. 29 (2), 194-199 (1986).
32. 2 binding characteristics with phenylalkylamine hallucinogens, Eur. J. Pharmacol. 145 (3), 291-297 (1988).
33. 2 involvement in the mechanism of action of hallucinogenic agents, Life Sci. 35 (25), 2505-2511 (1984).
34. Glennon, R.A., Central serotonin receptors as targets for drug research, J. Med. Chem. 30 (1), 1-12 (1987).
35. Teitler, M., Leonhardt, S., Appel, N.M., DeSouza, E.B. and Glennon, R., Receptor pharmacology of MDMA and related hallucinogens, Ann. N. Y. Acad. Sci. 600 (15), 626-639 (1990).
36. 3H]MDL 100.907, Naunyn Schmiedebergs Arch. Pharmacol. 356 (4), 446-454 (1997).
37. Boehm, H.-J., Klebe, G. and Kubinyi, H., In: Wirkstoffdesign, Heidelberg; Berlin; Oxford: Spektrum, Akad. Verl.: p 384 (1996).
38. Zbinden, P., Dobler, M., Folkers, G. and Vedani, A., PrGen: Pseudoreceptor modeling using receptor-mediated ligand alignment and pharmacophore equilibration, Quant. Struct.-Act. Relat. 17, 122-130 (1998).
39. Kennard, O., Giacovazzo, C., Horn, A.S., Mongiorgi, R. and Riva di Sanseverino, L., Crystal and molecular structure of the psychotropic drug 2-(4-ethyl-2,5-dimetoxyphenyl)-1-methylethylamine (4-ethyl-2,5-dimethoxyamphetamine), J. Chem. Soc. Perkin Trans. II. 10, 1160-1163 (1974).
40. Falkenberg, G., The crystal and molecular structure of bufotenine, 5-hydroxy-(N,N)-dimethyltryptamine, Acta Cryst. B 28, 3219-3228 (1972).
41. Cambridge Crystallographic Database Crystallographic Data Centre, University Chemical Laboratory, Cambridge, U.K.
42. SYBYL Version 6.3, Theory Manual, Tripos Inc. 1699, S. Hanley Road, St. Louis, Missouri; 1996.
43. Oberlender, R., Pfaff, R.C., Johnson, M.P., Huang, X. and Nichols, D.E., Stereoselective LSD-like activity in d-lysergic acid amides of (R)- and (S)-2-aminobutane, J. Med. Chem. 35 (2), 203-211 (1992).
44. Clark, M., Cramer III, R.D. and Van Opdenbosch, N., Validation of the General Purpose Tripos 5.2 Force Field, J. Comput. Chem. 10, 982-1012 (1989).
45. 2-Rezeptor, Dissertation, Freie Universität Berlin, Berlin 1990.
46. Mohamadi, F., Richards, N.G.J., Guida, W.C., Liskamp, R., Lipton, M., Caufield, C., Chang, G., Hendrickson, T. and Still, W.C., MacroModel - An integrated software system for modeling organic and bioorganic molecules using molecular mechanics, J. Comput. Chem. 11, 440-467 (1990).
47. Cramer, C.J. and Truhlar, D.G., AM1-SM2 and PM3-SM3 parameterized SCF solvation models for free energies in aqueous solution, J. Comp.-Aided Molec. Design, 6, 629-666 (1992). Distributed by QCPE, University of Indiana, Bloomington, Indiana, USA (Program 606).
48. Blaney, J.M., Weiner, P.K., Dearing, A., Kollman, P.A., Jorgensen, E.C., Oatley, S.J., Burridge, J.M. and Blake, J.F., Molecular mechanics simulation of protein-ligand interactions: binding to a thyroid analogues to prealbumin, J. Am. Chem. Soc. 104, 6424-6434 (1982).
49. Vedani, A., Zbinden, P., Snyder, J.P. and Greenidge, P.A., Pseudoreceptor modeling: The construction of three-dimensional receptor surrogates, J. Am. Chem. Soc. 117, 4987-4994 (1995).
50. Vedani, A. and Huhta, D.W., A new force field for modeling metalloproteins, J. Am. Chem. Soc. 112, 4759-4767 (1990).
51. Searle, M.S. and Williams, D.H., The cost of conformational order: entropy changes in molecular associations, J. Am. Chem. Soc. 114, 10690-10697 (1992).
52. Still, W.C., Templzyk, A., Hawley, R.C. and Hendrickson, T., Semianalytical treatment of solvation for molecular mechanics and dynamics, J. Am. Chem. Soc. 112, 6127-6129 (1990).
53. Nichols, D.E., Pfister, W.R. and Yim, G.K.W., LSD and phenethylamine hallucinogens: new structural analogy and implications for receptor geometry, Life Sci. 22 (24), 2165-2170 (1978).
54. 2A agonists, Pharm. Pharmacol. Lett. 3, 260-263 (1994).
55. 2 receptor: identification of amino acids necessary for ligand binding and receptor activation, Mol. Pharmacol. 43 (6), 931-940 (1993).
56. 2A receptor, J. Med. Chem. 41 (26), 5148-5149 (1998).
57. Monte, A.P., Structure-activity relationships of hallucinogens: design, synthesis, and pharmacological evaluation of a series of conformationally restricted phenethylamines, thesis, Purdue University, 1995.
58. 2, J. Med. Chem. 39, 2953-2961 (1996).
59. Monte, A.P., Marona-Lewicka, D., Lewis, M.M., Mailman, R.B., Wainscott, D.B., Nelson, D.L. and Nichols, D.E., Substituted naphthofurans as hallucinogenic phenethylamine-ergoline hybrid molecules with unexpected muscarinic antagonist activity, J. Med. Chem. 41 (12), 2134-2145 (1998).
60. Nichols, D.E., Snyder, S.E., Oberlender, R., Johnson, M.P. and Huang, X., 2,3-Dihydrobenzofuran analogues of hallucinogenic phenethylamines, J. Med. Chem. 34, 276-281 (1991).
61. 2A/2C agonist, J. Med. Chem. 37 (25), 4346-4351 (1994).
62. Shulgin, A. and Shulgin, A., PIHKAL. A chemical love story, Transform Press, Berkeley 1991.