Novel ligands lacking a positive charge for the δ- and μ-opioid receptors

Journal of Medicinal Chemistry

Volumn 43, Issue 4, 2000, Pages 551-559

  Schiller, Peter W ^a   Berezowska, Irena ^a   Nguyen, Thi M D ^a   Schmidt, Ralf ^a,d   Lemieux, Carole ^a   Chung, Nga N ^a   Falcone Hindley, Margaret L ^b   Yao, Wenqing ^b,e   Liu, Josephine ^b   Iwama, Seiji ^b,c   Smith III, Amos B ^b   Hirschmann, Ralph F ^b  

^a CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c Osaka Prefecture University   (Japan)

^d ASTRAZENECA   (United Kingdom)

^e DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLO(PROLYLPHENYLALANYL DEXTRO TRYPTOPHYL 4 FLUOROPHENYLALANYLTHREONYLPHENYLALANYL); CYCLO(PROLYLPHENYLALANYL DEXTRO TRYPTOPHYLLYSYLTHREONYLPHENYLALANYL); DELTA OPIATE RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; MU OPIATE RECEPTOR; NEUROKININ 1 RECEPTOR; NEUROKININ 1 RECEPTOR ANTAGONIST; SOMATOSTATIN DERIVATIVE; SOMATOSTATIN RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BRAIN; DRUG RECEPTOR BINDING; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIGAND BINDING; MEMBRANE BINDING; NONHUMAN; PEPTIDE SYNTHESIS; RAT;

ANIMALS; BINDING, COMPETITIVE; BRAIN; GUINEA PIGS; ILEUM; LIGANDS; MALE; MICE; MUSCLE CONTRACTION; MUSCLE, SMOOTH; NARCOTIC ANTAGONISTS; OLIGOPEPTIDES; PEPTIDES, CYCLIC; RADIOLIGAND ASSAY; RATS; RECEPTORS, NEUROKININ-1; RECEPTORS, OPIOID, MU; STRUCTURE-ACTIVITY RELATIONSHIP; VAS DEFERENS;

EID: 0034000876     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990461z     Document Type: Article

References (64)

1. 2; TFA, trifluoroacetic acid; THF, tetrahydrofuran; U69,593, (5α,7α,8β)-(-)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5] dec-8-yl]benzeneacetamide.
2. Bikker, J. A.; Trumpp-Kallmeyer, S.; Humblet, C. G-Protein Coupled Receptors: Models, Mutagenesis, and Drug Design. J. Med. Chem. 1998, 41, 2911-2927.
3. (a) Gilman, A. G. G-Proteins: Transducers of Receptor-Generated Signals. Annu. Rev. Biochem. 1987, 56, 615-649.
4. (b) Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M.; Modeling of G-Protein Coupled Receptors: Application to Dopamine, Adrenaline, Seratonin, and Mammalian Opsin Receptors. J. Med. Chem. 1992, 35, 3448-3462.
5. Strader, C. D.; Fong, T. M.; Candelore, M. R.; Cascieri, M. A.; Weinberg, D.; Bayne, M. Adrenergic Receptors as Models for the Family of G-Protein Coupled Receptors. Pharmacol. Commun. 1995, 6, 195-202.
6. Strader, C. D.; Sigal, I. S.; Register, R. B.; Candelore, M. R.; Rands, E.; Dixon, R. A. F. Identification of Residues Required for Ligand Binding to the β Adrenergic Receptor. Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 4384-4387.
7. Strader, C. D.; Sigal, I. S.; Candelore, M. R.; Rands, E.; Hill, W. S.; Dixon, R. A. F. Conserved Aspartic Acid Residues 79 and 113 of the β Adrenergic Receptor have Different Roles in Receptor Function. J. Biol. Chem. 1988, 263, 10267-10271.
8. Strader, C. D.; Gaffney, Y.; Sugg, E. E.; Candelore, M. M.; Keys, R., Patchett, A. A.; Dixon, R. A. F. Allele-Specific Activation of Genetically Engineered Receptors. J. Biol. Chem. 1991, 266, 5-8.
9. Rees, D. C.; Hunter, J. C. Opioid Receptors. In Comprehensive Medicinal Chemistry; Emmet, J. C., Ed.; Pergamon Press: New York, 1990; pp 805-846.
10. Morgan, B. A.; Smith, C. F. C.; Waterfield, A. A.; Hughes, J.; Kosterlitz, H. W. Structure-Activity Relationships of Methionine-Enkephalin. J. Pharm. Pharmacol. 1976, 28, 660-661.
11. Büscher, H. H.; Hill, R. C.; Römer, D.; Cardinaux, F.; Closs, A.; Hauser, D.; Pless, J. Evidence for Analgesic Activity of Enkephalin in the Mouse. Nature (London) 1976, 261, 423-425.
12. Ling, N.; Guillemin, R. Morphinomimetic Activity of Synthetic Fragments of β-Lipotropin and Analogues. Proc. Natl. Acad. Sci. U.S.A. 1976, 73, 3308-3310.
13. Lemaire, S.; Belleau, B.; Jolicoeur, F. B. Agonist and Antagonist Opioid Activity of Axial and Equatorial Conformations of S-methyl- and S-Allyl-Morphinans. Eur. J. Pharmacol. 1994, 258, 111-118.
14. Rónai, A. Z.; Botyánszki, J.; Hepp, J.; Medzihradszky, K. A Novel Opioid Structure Which Accepts Protonated as well as Non-Protonated Nitrogen: A Family of Pure, Delta Receptor Selective Antagonists. Life Sci. 1992, 50, 1371-1378.
15. (a) Rónai, A. Z.; Magyar, A.; Medzihradszky, K. Kinetic Parameters of Antagonism by the Delta Opioid Receptor Selective Peptide Boc-Tyr-Pro-Gly-Phe-Leu-Thr Against Selective and Non-Selective Agonists in the Mouse Vas Deferens. Neuropeptides 1993, 25, 127-129.
16. 1 Analogues. Arch. Int. Pharmacodyn. 1995, 330, 361-369.
17. Balboni, G.; Guerrini, R.; Salvadori, S.; Tomatis, R.; Bryant, S. D.; Bianchi, C.; Attila, M.; Lazarus, L. H. Opioid Diketopiperazines: Synthesis and Activity of a Prototypic Class of Opioid Antagonists. Biol. Chem. 1997, 378, 19-29.
18. Evans, C. J.; Keith, D. E., Jr.; Morrison, H.; Magendzo, K.; Edwards, R. H. Cloning of a Delta Opioid Receptor by Functional Expression. Science 1992, 258, 1952-1955.
19. Kieffer, B. L.; Befort, K.; Gaveriaux-Ruff, C.; Hirth, C. G. The δ-Opioid Receptor: Isolation of a c-DNA by Expression Cloning and Pharmacological Characterization. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 12048-12052.
20. Kong, H.; Raynor, K.; Yasuda, K.; Moe, S. T.; Portoghese, P. S.; Bell, G. I.; Reisine, T. A Single Residue, Aspartic Acid 95, in the Delta Opioid Receptor Specifies Selective High Affinity Agonist Binding. J. Biol. Chem. 1993, 268, 23055-23058.
21. Befort, K.; Tabbara, L.; Bausch, S.; Chavkin, C.; Evans, C.; Kieffer, B. The Conserved Aspartate Residue in the Third Putative Transmembrane Domain of the δ-Opioid Receptor Is not the Anionic Counterpart for Cationic Opiate Binding but Is a Constituent of the Receptor Binding Site. Mol. Pharmacol. 1996, 49, 216-223.
22. This residue's importance is still controversial (P. Portoghese, private communication).
23. A term introduced by: Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Freidinger, R. M.; Whitter, W. I.; Lundell, G. F.; Veber, D. F.; Anderson, P. S.; Chang, R. S. L.; Lotti, V. J.; Cerino, D. J.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirshfield, J. Methods for Drug Discovery: Development of Potent, Selective, Orally Effective Cholecystokinin Antagonists. J Med. Chem. 1988, 31, 2235-2246.
24. Hirschmann, R.; Hynes, J., Jr.; Cichy-Knight, M. A.; van Rijn, R. D.; Sprengeler, P. A.; Spoors, P. G.; Shakespeare, W. C.; Pietranico-Cole, S.; Barbosa, J.; Liu, J.; Yao, W. Q.; Rohrer, S.; Smith, A. B., III. Modulation of Receptor and Receptor Subtype Affinities using Diastereomeric and Enantiomeric Monosaccharide Scaffolds as a Means to Structural and Biological Diversity. A New Route to Ether Synthesis. J. Med. Chem. 1998, 41, 1382-1391.
25. Hoffsommer, R. D.; Taub, D.; Wendler, N. L. Coupling Reactions in the Synthesis of Amitriptyline. J. Med. Chem. 1965, 8, 555-556.
26. Hirschmann, R.; Yao, W.; Cascieri, M. A.; Strader, C. D.; Maechler, L.; Cichy-Knight, M. A.; Hynes, J., Jr.; van Rijn, R. D.; Sprengeler, P. A.; Smith, A. B., III. Synthesis of Potent Cyclic Hexapeptide NK-1 Antagonists. Use of a Minilibrary in Transforming a Peptidal Somatostatin Receptor Ligand into an NK-1 Receptor Ligand via a Polyvalent Peptidomimetic. J. Med. Chem. 1996, 39, 2441-2448.
27. Veber, D. F.; Freidinger, R. M.; Perlow, D. S.; Paleveda, W. J., Jr.; Holly, F. W.; Strachan, R. G.; Nutt, R. F.; Arison, B. H.; Homnick, C.; Randall, W. C.; Glitzer, M. S.; Saperstein, R.; Hirschmann, R. A Potent Cyclic Hexapeptide Analogue of Somatostatin. Nature (London) 1981, 292, 55-58.
28. Schmidt, R.; Vogel, D.; Mrestani-Klaus, C.; Brandt, W.; Neubert, K.; Chung, N. N.; Lemieux, C.; Schiller, P. W. Cyclic β-Casomorphin Analogues with Mixed μ Agonist/δ Antagonist Properties: Synthesis, Pharmacological Characterization and Conformational Aspects. J. Med. Chem. 1994, 37, 1136-1144.
29. Applied Biosystems Inc., Publication No. 35; FastMoc 0.25 and 0.1 μmol on the model 431A.
30. (a) Hirschmann, R.; Yao, W.; Arison, B.; Maechler, L.; Rosegay, A.; Sprengeler, P. A.; Smith, A. B., III. Synthesis of the First Tricyclic Homodetic Peptide. Use of Coordinated Orthogonal Deprotection to Achieve Directed Closure. Tetrahedron 1998, 54, 7179-7202.
31. (b) Hirschmann, R.; Yao, W.; Arison, B.; Maechler, L.; Rosegay, A.; Sprengeler, P. A.; Smith, A. B., III. The First Synthesis of a Tricyclic Homodetic Peptide Employing Coordinated Ring Closure. Tetrahedron Lett. 1996, 37, 5637-5640.
32. Hünig, S.; Schwarz, H. Farbe und Konstitution IV. Farbstoffe mit gekreuzten Absorptionsystemen II. Liebigs Ann. Chem. 1956, 599, 131-139.
33. Schiller, P. W.; Nguyen, T. M.-D.; Chung, N. N.; Lemieux, C. Dermorphin Analogues Carrying an Increased Positive Net Charge in Their "Message" Domain Display Extremely High μ-Opioid Receptor Selectivity. J. Med. Chem. 1989, 32, 698-703.
34. Schiller, P. W.; Weltrowska, G.; Nguyen, T. M.-D.; Wilkes, B. C.; Chung, N. N.; Lemieux, C. TIPP[ψ]: A Highly Potent and Stable Pseudopeptide δ Opioid Receptor Antagonist with Extraordinary δ Selectivity, J. Med. Chem. 1993, 36, 3182-3187.
35. For a mini-review, see: Schiller, P. W.; Weltrowska, G.; Schmidt, R.; Berezowska, B. C.; Nguyen, T. M.-D.; Lemieux, C.; Chung, N. N.; Carpenter, K. A.; Wilkes, B. C. Subtleties of Structure-Agonist vs Antagonist Relationships of Opioid Peptides and Peptidiomimetics. J. Recept. Sign. Trans. Res. 1999, 19, 573-588.
36. See, for example: (a) Bäckbro, K.; Löwgren, S.; Österlund, K.; Atepo, J.; Unge, T.; Hultén, J.; Bonham, N. M.; Schaal, W.; Karlén, A.; Hallberg, A. Unexpected Binding Mode of a Cyclic Sulfamide HIV-1 Protease Inhibitor. J. Med. Chem. 1997, 40, 898-902.
37. (b)Smith, A. B., III; Hirschmann, R.; Pasternak, A.; Yao, W.; Sprengler, P. A. An Orally Bioavailable Pyrrolinone Inhibitor of HFV-1 Protease: Computational Analysis and X- ray Crystal Structure of the Enzyme Complex. J. Med. Chem. 1997, 40, 2440-2444.
38. (c) Allen, K. N.; Bellamacina, C. R.; Ding, X.; Jeffery, C. J.; Mattos, C.; Petsko, G. A.; Ringe, D. An Experimental Approach to Mapping the Binding Surfaces of Crystalline Proteins. J. Phys. Chem. 1996, 100, 2605-2611.
39. (d) Mattos, C.; Rasmussen, B.; Ding, X.; Petsko, G. A.; Ringe, D. Analgous Inhibitors of Elastase Do Not Always Bind Analogously. Nature, Struct. Biol. 1994, 1, 55-58.
40. (e) Mattos, C.; Ringe, D. Multiple Binding Modes. In Drug Design Theory; Methods and Applications; Kubingi, H., Ed.; Escom: Leiden, 1993; pp 225-254.
41. (f) Rich, D. H.; Boparai, A. S.; Bernatowicz, M. S. Synthesis of a 3-Oxo-4-(S)-Amino Acid Analogue of Pepstatin. A New Inhibitor of Carboxyl Proteases. Biochem. Biophys. Res. Commun. 1982, 104, 1127-1133.
42. 8-mimicking side chain binds somatostatin receptors via an atypical binding mode.
43. (a) Clinton, R. O.; Manson, A. J.; Stonner, F. W.; Beyler, A. L.; Potts, G. O.; Arnold, A. Steriodal [3,2-c] Pyrazoles. J. Am. Chem. Soc. 1959, 81, 1513.
44. (b) Clinton, R. O.; Manson, A. J.; Stonner, F. W.; Neuman, H. C.; Christiansen, R. G.; Clark, R. L.; Ackerman, J. H.; Page, D. F.; Dean, J. W.; Dickinson, W. B.; Carabateas, C. Steroidal [3,2-c] Pyrazoles. II. Androstanes, 19-Norandrostanes and their Unsaturated Analogues. J. Am. Chem. Soc. 1961, 83, 1478.
45. Hirschmann, R.; Buchschacher, P.; Steinberg, N. G.; Fried, J. H.; Ellis, R.; Kent, G. J.; Tishler, M. Synthesis and Structure of Steroidal Pregn-4-eno- and 5a-Pregnano[3,2-c]-Pyrazoles. A Novel Class of Potent Antiinflammatory Steroids. J. Am. Chem. Soc. 1964, 36, 1520.
46. 2-Adrenergic Receptor. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 12322-12327.
47. (a) Burley, S. K.; Petsko, G. A. Weakly Polar Interactions in Proteins. Adv. Protein Chem. 1988, 39, 125-189.
48. (b) Levitt, M.; Perutz, M. F. Aromatic Rings Act as Hydrogen Bond Acceptors. J. Mol. Biol. 1988, 201, 751-754.
49. Fukuda, K.; Kato, S.; Mori, K. Location of Regions of the Opioid Receptor Involved in Selective Agonist Binding. J. Biol. Chem. 1995, 270, 6702-6209.
50. (a) Befort, K.; Zilliox, C.; Filliol, D.; Yue, S. Y.; Kieffer, B. L. Constitutive Activation of the δ Opioid Receptor by Mutations in Transmembrane Domains III and VII. J. Biol. Chem. 1999, 274, 18574-18581.
51. (b) Befort, K.; Tabbara, L.; Kling, D.; Maigret, B.; Kieffer, B. L. The Role of Aromatic Transmembrane Residues of the δ Opioid Receptor in Ligand Recognition. J. Biol. Chem. 1996, 271, 10161-10168.
52. Schiller, P. W.; DiMaio, J. Aspects of Conformational Restriction in Biologically Active Peptides. In Peptides: Structure and Function; Hruby, V. J., Rich, D. H., Eds.; Pierce Chemical Co.: Rockford, IL, 1983; pp 269-278.
53. Terenius, L. Somatostatin and ACTH are Peptides with Partial Antagonist-Like Selectivity for Opiate Receptors. Eur. J. Pharmacol. 1976, 38, 211.
54. (a) Pelton, J. T.; Kazmierski, W.; Gulya, K.; Yamamura, H. I.; Hruby, V. J. Design and Synthesis of Conformationally Constrained Somatostatin Analogs with High Potency and Specificity for μ Opioid Receptors. J. Med. Chem. 1986, 29, 2370-2375.
55. (b) Kazmierski, W.; Wire, W. S.; Lui, G. K.; Knapp, R. J.; Shook, J. E.; Burks, T. F.; Yamamura, H. I.; Hruby, V. J. Design and Synthesis of Somatostatin Analogues with Topographical Properties that Lead to Highly Potent and Specific μ Opioid Receptor Antagonists with Greatly Reduced Binding at Somatostatin Receptors. J. Med. Chem. 1988, 31, 2170-2177.
56. (c) Bonner, G. G.; Davis, P.; Stropova, D.; Ferguson, R.; Yamamura, H. I.; Porreca, F.; Hruby, V. J. Opioid Peptides: Simultaneous δ Agonism/μ Antagonism in Somatostatin Analogues. Peptides 1997, 18, 93-100.
57. Hirschmann, R.; Nicolaou, K. C.; Pietranico, S.; Leahy, E. M.; Salvino, J.; Arison, B.; Cichy, M. A.; Spoors, P. G.; Shakespeare, W. C.; Sprengeler, P. A.; Hamley, R.; Smith, A. B., III; Reisine, T.; Raynor, K.; Maechler, L.; Donaldson, C.; Vale, W.; Freidinger, R. M.; Cascieri, M. R.; Strader, C. D. De Novo Design and Synthesis of Somatostatin Non-Peptide Peptidomimetics Utilizing β-D-Glucose as a Novel Scaffolding. J. Am. Chem. Soc. 1993, 115, 12550-12568.
58. Dugos, J. H.; Yonan, E. E.; Scares, M. G.; Goodmonson, O. J.; Getman, D. P.; Periana, R. A.; Beck, G. R. A Convenient Asymmetric Synthesis of the Unnatural Amino Acid 2,6-Dimethyl-L-tyrosine. Synthesis 1992, 741-743.
59. Paton, W. D. M. The Action of Morphine and Related Substances on Contraction and on Acetylcholine Output of Coaxially Stimulated Guinea Pig Ileum. Br. J. Pharmacol. 1957, 12, 119-127.
60. Schiller, P. W.; Lipton, A.; Horrobin, D. F.; Bodanszky, M. Unsulfated C-terminal 7-Peptide of Cholecystokinin: A New Ligand of the Opiate Receptor. Biochem. Biophys. Res. Commun. 1978, 85, 1332-1338.
61. DiMaio, J.; Nguyen, T. M.-D.; Lemieux, C.; Schiller, P. W. Synthesis and Pharmacological Characterization In Vitro of Cyclic Enkephalin Analogues: Effects of Conformational Constraints on Opiate Receptor Selectivity. J. Med. Chem. 1982, 25, 1432-1438.
62. Kosterlitz, H. W.; Watt, A. J. Kinetic Parameters of Narcotic Agonists and Antagonists with Particular Reference to N-Allylnoroxymorphone (Naloxone). Br. J. Pharmacol. 1968, 33, 266-276.
63. McKnight, A. T.; Corbett, A. D.; Kosterlitz, H. W. Increase in Potencies of Opioid Peptides after Peptidase Inhibition. Eur. J. Pharmacol. 1983, 86, 393-402.
64. 50) of an Enzymatic Reaction. Biochem. Pharmacol. 1973, 22, 3099-3102.