1,2,3-Trisubstituted Cyclopropanes as Conformationally Restricted Peptide Isosteres: Application to the Design and Synthesis of Novel Renin Inhibitors

Journal of Medicinal Chemistry

Volumn 35, Issue 10, 1992, Pages 1710-1721

  Martin, Stephen F ^a   Austin, Richard E ^a   Oalmann, Christopher J ^a   Baker, William R ^b   Condon, Stephen L ^b   deLara, Ed ^b   Rosenberg, Saul H ^b   Spina, Kenneth P ^b   Stein, Herman H ^b   Cohen, Jerome ^b   Kleinert, Hollis D ^b  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^b ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 CYCLOHEXYL 6 METHYL 2 [[N [[3 PHENYL 2 (MORPHOLINOCARBONYL)CYCLOPROPYL]CARBONYL] 3 (4 THIAZOLYL)ALANYL]AMINO] 3,4 HEPTANEDIOL; ANGIOTENSIN; ANTIHYPERTENSIVE AGENT; RENIN; RENIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG CONFORMATION; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; NONHUMAN; PRIORITY JOURNAL; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; BINDING SITES; CYCLOPROPANES; DRUG DESIGN; ENZYME INHIBITORS; MOLECULAR SEQUENCE DATA; OXIDATION-REDUCTION; PROTEIN CONFORMATION; RENIN; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S.;

EID: 0026642037     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00088a005     Document Type: Article

References (74)

1. Farmer, P. S. Bridging the Gap between Bioactive Peptides and Nonpeptides: Some Perspectives in Designs. In Drug Design; Ariens, E. J., Ed.; Academic Press Inc.: New York, 1980; Vol. X, pp 119-143.
2. Hruby, V. J. Conformational Restrictions of Biologically Active Peptides via Amino Acid Side Chain Groups. Life Sciences 1982, 31, 189-199.
3. Spatola, A. F. Peptide Backbone Modifications: A Structure-Activity Analysis of Peptides Containing Amide Bond Surrogates. Conformational Constraints, and Related Backbone Replacements. In Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins; Weinstein, B., Ed; Marcel Dekker, 1983; Vol. 7, pp 267-357.
4. Toniolo, C. Conformationally Restricted Peptides Through Short-Range Cyclizations. Int. J. Peptide Protein Res. 1990, 35, 287-300.
5. Hruby, B. J.; Al-Obeidi, F.; Kazmierski, W. Emerging Approaches in the Molecular Design of Receptor-Selective Peptide Ligands: Conformational, Topographical and Dynamic Considerations. Biochem. J. 1990, 268, 249-262
6. Freidinger, R. M.; Veber, D. F.; Perlow, D. S.; Brooks, J. R.; Saperstein, R. Bioactive Conformation of Luteinizing Hormone-Releasing Hormone: Evidence from a Conformationally Constrained Analog. Science 1980, 210, 656-658.
7. Freidinger, R. M.; Perlow, D. S.; Veber, D. F. Protected Lactam-Bridged Dipeptides for Use as Conformational Constraints in Peptides. J. Org. Chem. 1982, 47, 104-109.
8. Kemp, D. S.; McNamara, P. Amino Acid Derivatives That Stabilize Secondary Structures of Polypeptides II. The Most Stable Conformation of Peptides Containing 3-Amino-2-piperidone-6-carboxylic Acid (Acp). Tetrahedron Lett. 1982, 23, 3761-3164
9. Krstenansky, J. L.; Baranowski, R. L.; Currie, B. L. A New Approach to Conformationally Restricted Peptide Analogs: Rigid 5-Bends. 1. Enkephalin as an Example. Biochem. Biophys. Res. Commun. 1982, 109, 1368-1374
10. Thorsett, E. D.; Harris, E. E.; Aster, S.; Peterson, E. R.; Taub, D.; Patchett, A. A. Dipeptide Mimics. Conformationally Restricted Inhibitors of Angiotensin-Converting Enzyme. Biochem. Biophys. Res. Commun. 1983, 111, 166-171.
11. Kemp, D. S.; McNamara, P. E. Conformationally Restricted Cyclic Nonapeptides Derived from L-Cysteine and LL-3-Amino-2-piperidone-6-carboxylic Acid (LL-Acp), a Potent 5-Tum-Inducing Dipeptide Analogue. J. Org. Chem. 1985, 50, 5834-5838
12. Nagai, U.; Sato, K. Synthesis of a Bicyclic Dipeptide with the Shape of β-Turn Central Part. Tetrahedron Lett. 1985, 26, 647-650
13. Feigel, M. 2,8-Dimethyl-4-(carboxymethyl)-6-(aminomethyl)phenoxathiin S-Dioxide: An Organic Substitute for the 5-Turn in Peptides? J. Am. Chem. Soc. 1986, 108, 181-182.
14. Zydowsky, T. H.; Dellaria, J. F., Jr.; Nellans, H. N. Efficient and Versatile Synthesis of Dipeptide Isosteres Containing γ- or β-Lactams. J. Org. Chem. 1988, 53, 5607-5616
15. Thaisrivongs, S.; Pals, D. T.; Turner, S. T.; Kroll, L. T. Conformationally Constrained Renin Inhibitory Peptides: 7-Lactam-Bridged Dipeptide Isostere as Conformational Restriction. J. Med. Chem. 1988, 31, 1369-1376
16. Yu, K.-L.; Rajakumar, G.; Srivastava, L. K.; Mishra, R. K.; Johnson, R. L. Dopamine Receptor Modulation by Conformationally Constrained Analogues of Pro-Leu-Gly-NH2. J. Med. Chem. 1988, 31, 1430-1436
17. Kahn, M.; Wilke, S.; Chen, B.; Fujita, K. Nonpeptide Mimetics of 5-turns: A facile Oxidative Intramolecular Cycloaddition of an Azodicarbonyl System. J. Am. Chem. Soc. 1988, 110, 1638-1639
18. Kemp, D. S.; Carter, J. S. Amino Acid Derivatives that Stabilize Secondary Structures of Polypeptides. 4. Practical Synthesis of 4-Alkylamino-3-cyano-6-azabicyclo[3.2.1]oct-3-enes (Ben Derivatives) as 7-Turn Templates. J. Org. Chem. 1989, 54, 109-115
19. Wolf, J.-P.; Rapoport, H. Conformationally Constrained Peptides. Chirospecific Synthesis of 4-Alkyl-Substituted 7-Lactam-Bridged Dipeptides from γ-Aspartic Acid. J. Org. Chem. 1989, 54, 3164-3173
20. Kahn, M.; Bertenshaw, S. The Incorporation of 5-Turn Prosthetic Units into Merrifield Solid Phase Peptide Synthesis. Tetrahedron Lett. 1989, 30, 2317-2320
21. Garvey, D. S.; May, P. D.; Nadzan, A. M. 3,4-Disubstituted 7-Lactam Rings as Conformationally Constained Mimics of Peptide Derivatives Containing Aspartic Acid or Norleucine. J. Org. Chem. 1990, 55, 936-940
22. Ernest, I.; Kalvoda, J.; Rihs, G.; Mutter, M. Three Novel Mimics for the Construction of Sterically Constrained Protein Turn Models. Tetrahedron Lett. 1990, 31, 4011-4014.
23. Ede, N. J.; Rae, I. D.; Hearn, M. T. W. Synthesis of a New Protected Lactam-Bridged Dipeptide. Tetrahedron Lett. 1990, 31, 6071-6074
24. Holladay, M. W.; Nadzan, A. M. Synthesis of α-Benzyl γ-Lactam, α-Benzyl γ-Lactam, and γ-Benzylproline Derivatives as Conformationally Restricted Analogues of Phenylalaninamide. J. Org. Chem. 1991, 56, 3900-3905.
25. Hinds, M. G.; Welsh, J. H.; Brennand, D. M.; Fisher, J.; Glennie, M. J.; Richards, N. G. J.; Turner, D. L.; Robinson, J. A. Synthesis, Conformational Properties, and Antibody Recognition of Peptides Containing β-Turn Mimetics Based on α-Alkylproline Derivatives. J. Med. Chem. 1991, 34, 1777-1789
26. Kahn, M.; Devens, B. The Design and Synthesis of a Nonpeptide Mimic of an Immunosuppressing Peptide. Tetrahedron Lett. 1986, 27, 4841-4844
27. Flynn, G. A.; Giroux, E. L.; Dage, R. C. An Acyl-Iminium Ion Cyclization Route to a Novel Conformationally Restricted Dipeptide Mimic: Applications to Angiotensin-Converting Enzyme Inhibition. J. Am. Chem. Soc. 1987, 109, 7914-7915.
28. Kahn, M.; Chen, B.; Zieske, P. The Design and Synthesis of a Nonpeptide Mimic of Erabutoxin. Heterocycles 1987, 25, 29-31
29. Olson, G. L.; Voss, M. W.; Hill, D. W.; Kahn, M.; Madison, V. S.; Cook, C. M. Design and Synthesis of a Protein β-Turn Mimetic. J. Am. Chem. Soc. 1990, 112, 323-333.
30. Kazmierski, W. M.; Yamamuia, H. I.; Hruby, V. J. Topographic Design of Peptide Neurotransmitters and Hormones on Stable Backbone Templates: Relation of Conformation and Dynamics to Bioactivity. J. Am, Chem. Soc. 1991, 113, 2275
31. Shimamoto, K.; Ishida, M.; Shinozaki, H.; Ohfune, Y, Synthesis of Four Diastereomeric L-2-(Carboxycyclopropyl)glycines. Conformationally Constrained 1-Glutamate Analogues. J. Org. Chem. 1991, 56, 4167-4176
32. Martin, S. F.; Austin, R. E.; Oalmann, C. J. Stereoselective Synthesis of 1,2,3-Trisubstituted Cyclopropanes as Novel Dipeptide Isosteres. Tetrahedron Lett. 1990, 31, 4731-4734
33. Melnick, M. J.; Bisaha, S. N.; Gammill, R. B. Conformationally Restricted P-Pt’ Transition State Analogues. Synthesis of 1(R), 3(R) [1(,S), 2(S)] 3-[3-Cyclohexyl-2-[(Boc)amino]-l-hydroxypropyl]-2,2-dimethylcyclopropane Carboxylic Acids. Tetrahedron Lett. 1990, 31, 961-964
34. Stammer, C. H. Cyclopropane Amino Acids (2,3-and 3,4-Methanoamino Acids). Tetrahedron 1990, 46, 2231-2254
35. Jupp, R, A.; Dunn, B. M.; Jacobs, J. W.; Vlasuk, G.; Arcuri, K. E.; Veber, D. F.; Perlow, D. S.; Payne, L. S.; Boger, J.; de Laszlo, S.; Chakravarty, P. K.; Ten Broeke, J.; Hangauer, D. G.; Ondeyka, D.; Greenlee, W. J.; Kay, J. The Selectivity of Statine-Based Inhibitors Against Various Human Aspartic Proteinases. Biochem. J. 1990, 265, 871-878
36. Foundling, S. I.; Cooper, J.; Watson, F. E.; Cleasby, A.; Pearl, L. H.; Sibanda, B. L.; Hemmings, A.; Wood, S. P.; Blundell, T. L.; Valler, M. J.; Norey, C. G.; Kay, J.; Boger, J.; Dunn, B. M.; Leckie, B. J.; Jones, D. M.; Atrash, B.; Hallett, A.; Szelke, M. High Resolution X-ray Analyses of Renin Inhibitor-Aspartic Proteinase Complexes. Nature 1987, 327, 349-352.
37. Blundell, T. L.; Cooper, J.; Foundling, S. I.; Jones, D. M.; Atrash, B.; Szelke, M. On the Rational Design of Renin Inhibitors: X-ray Studies of Aspartic Proteinases Complexed with Transition-State Analogues. Biochemistry 1987, 26, 5585-5590.
38. Cooper, J. B.; Foundling, S. I.; Blundell, T. L.; Boger, J.; Jupp, R. A.; Kay, J. X-ray Studies of Aspartic Proteinase-Statine Inhibitor Complexes. Biochemistry 1989, 28, 8596-8603
39. Suguna, K.; Padlan, E. A.; Smith, C. W.; Carlson, W. D.; Davies, D. R. Binding of a Reduced Peptide Inhibitor to the Aspartic Proteinase from Rhizopus Chinensis: Implications for a Mechanism of Action. Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 7009-7013
40. James, M. N. G.; Sielecki, A. R., Aspartic Proteinases and Their Catalytic Pathway. Biological Macromolecules and Assemblies; Jurnak, F. A., McPherson, A., Eds.; Wiley: New York, 1987, Vol. 3, pp 413-482.
41. Miller, M.; Schneider, J.; Sathyanarayana, B. K.; Toth, M. V.; Marshall, G. R.; Clawson, L.; Selk, L.; Kent, S. B. H.; Wlodawer, A. Structure of Complex of Synthetic HIV-1 Protease with a Substrate-Based Inhibitor at 2.3 A Resolution. Science 1989, 246, 1149-1152
42. Miller, M.; Swain, A. L.; Jaskolski, M.; Sathyanarayana, B. K.; Marshall, G. R.; Rich, D. H.; Kent, S. B. H.; Wlodawer, A. X-ray Analysis of HIV-1 Protease and Its Complexes with Inhibitors. Retroviral Proteases; Control of Maturation and Morphogenesis; Pearl, L., Ed; Macmillan Press: New York, 1990; pp 93-106
43. Erickson, J.; Neidhart, D. J.; VanDrie, J.; Kempf, D. J.; Wang, X. C.; Norbeck, D. W.; Plattner, J. J.; Rittenhouse, J. W.; Turon, M.; Wideburg, N.; Kohlbrenner, W. E.; Simmer, R.; Helfrich, R.; Paul, D. A.; Knigge, M. Design, Activity, and 2.8 A Crystal Structure of a C2 Symmetric Inhibitor Complexed to HIV-1 Protease. Science 1990, 249, 527-533
44. Swain, A. L.; Miller, M. M.; Green, J.; Rich, D. H.; Schneider, J.; Kent, S. B. H.; Wlodawer, A. X-ray Crystallographic Structure of a Complex Between a Synthetic Protease of Human Immunodeficiency Virus 1 and a Substrate-Based Hydroxyethylamine Inhibitor. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 8805-8809.
45. Jaskolski, M.; Tomasselli, A. G.; Sawyer, T. K.; Staples, D. G.; Heinrikson, R. L.; Schneider, J.; Kent, S. B. H.; Wlodawer, A. Structure at 2.5-A Resolution of Chemically Synthesized Human Immunodeficiency Virus Type 1 Protease Complexed with a Hydroxyethylene-Based Inhibitor. Biochemistry 1991, 30, 1600-1609
46. Watenpaugh, K. D.; Einspahr, H. M.; Finzel, B. C. ; Clancy, L. L.; Mulichak, A. M.; Holland, D. R.; Muchmore, S. W.; Poorman, R. A.; Hui, J. O.; Heinrikson, R. L.; Murakami, K.; Shoda, A.; Maggiora, L. L.; Sawer, T. K. Pept. Chem. Biol., Proc. 12th Am. Pept. Symp 1991, (June 16-21)
47. Peach, M. J. Renin-Angiotensin System: Biochemistry and Mechanisms of Action. Physiol. Rev. 1977, 57, 313
48. Ondetti, M. A.; Cushman, D. W. Enzymes of the Renin-Angiotensin System and Their Inhibitors. Ann. Rev. Biochem. 1982, 51, 283-308
49. Kleinert, H. D. Renin Inhibitors: Discovery and Development, An Overview and Perspective. Am. J. Hypertension 1989, 2, 800-808
50. Ocain, T. D.; Abou-Gharbia, M. Renin-Angiotensin System (RAS) Dependent Antihypertensive Agents: I. Renin Inhibitors. Drugs of the Future 1991, 16, 37-51
51. Kleinert, H. D.; Baker, W. R.; Stein, H. H. Renin Inhibitors. Adv. Pharm. 1991, 22, 207-250
52. Ondetti, M. A.; Cushman, D. W. Inhibition of the Reninangiotensin System. A New Approach to the Therapy of Hypertension. J. Med. Chem. 1981, 24, 355-361.
53. Thaisrivongs, S. Renin Inhibitors: A Promising New Class of Antihypertensive Agents. Drug News Perspect. 1988, 1, 11-16
54. Luly, J. R.; BaMaung, N.; Soderquist, J.; Fung, A. K. L.; Stein, H.; Kleinert, H. D.; Marcotte, P. A.; Egan, D. A.; Bopp, B.; Merits, L.; Bolis, G.; Greer, J.; Perun, T. J.; Plattner, J. J. Renin Inhibitors. Dipeptide Analogues of Angiotensinogen Utilizing a Dihydroxyethylene Transition-State Mimic at the Scissle Bond to Impart Greater Inhibitory Potency. J. Med. Chem. 1988, 31, 2264-2276.
55. Plattner, J. J.; Marcotte, P. A.; Kleinert, H. D.; Stein, H. H.; Greer, J.; Bolis, G.; Fung, A. K. L.; Bopp, B. A.; Luly, J. R.; Sham, H. L.; Kempf, D. J.; Rosenberg, S. H.; Dellaria, J. F.; De, B.; Merits, I.; Perun, T. J. Renin Inhibitors. Dipeptide Analogues of Angiotensinogen Utilizing a Structurally Modified Phenylalanine Residue to Impart Proteolytic Stability. J. Med. Chem. 1988, 31, 2277-2288
56. Glassman, H. N.; Kleinert, H. D.; Boger, R. S.; Moyse, D. M.; Griffiths, A. M.; Luther, R. R. Clinical Pharmacology of Enalkiren, a Novel Dipeptide Renin Inhibitor. J. Cardiovasc. Pharmacol. 1990, 16 (Suppl. 4), S76-S81
57. Rosenberg, S. H.; Kleinert, H. D.; Stein, H. H.; Martin, D. L.; Chekal, M. A.; Cohen, J.; Egan, D. A.; Tricarico, K. A.; Baker, W. R. Design of a Well-Absorbed Renin Inhibitor. J. Med. Chem. 1991, 34, 469-471
58. Nakagawa, N.; Mori, K. Synthesis of (3S,4S)-4-Methyl-3-heptanol and Its (3S,4R)-Isomer Employing Asymmetric Epoxidation Coupled with Regioselective Cleavage of Epoxides with Trimethylaluminum. Agric. Biol. Chem. 1984, 48, 2505-2510
59. Brown, C. A.; Ahuja, V. K. “P-2 Nickel” Catalyst with Ethylenediamine, a Novel System for Highly Stereospecific Reduction of Alkynes to cis-Olefins. J. Chem. Soc., Chem. Commun. 1973, 553-554.
60. Hatch, L. F.; Alexander, H. E. Preparation of cis-and trans-Cinnamyl Chloride. J. Am. Chem. Soc. 1950, 72, 5643-5645
61. Blankley, C. J.; Sauter, F. J.; House, H. O. Crotyl Diazoacetate (Acetic acid, diazo-, frans-2-butenyl ester). Organic Syntheses; John Wiley: New York, 1973; Coll. Vol. V, pp 258-263
62. Corey, E. J.; Myers, A. G. Efficient Synthesis and Intramolecular Cyclopropanation of Unsaturated Diazoacetic Esters. Tetrahedron Lett. 1984, 23, 3559-3562
63. Doyle, M. P.; Pieters, R. J.; Martin, S. F.; Austin, R. E.; Oalmann, C. J.; Muller, P. High Enantioselectivity in the Intramolecular Cyclopropanation of Allyl Diazoacetates Using a Novel Rhodium(II) Catalyst. J. Am. Chem. Soc. 1991, 113, 1423-1424
64. Jakovac, I. J.; Jones, J. B. Determination of Enantiomeric Purity of Chiral Lactones. A General Method Using Nuclear Magnetic Resonance. J. Org. Chem. 1979, 44, 2165-2168
65. Lynch, V. M.; Austin, R. E.; Martin, S. F.; George, T. The Determination of the Absolute Configuration of a Novel Dipeptide Isostere. Acta Crystallogr. 1991, C47, 1345-1347
66. Basha, A.; Lipton, M.; Weinreb, S. M. A Mild, General Method for Conversion of Esters to Amides. Tetrahedron Lett. 1977, 4171-4174
67. Hsiao, C. N.; Leanna, M. R.; Bhagavatula, L.; de Lara, E.; Zydowsky, T. M.; Horrom, B. W.; Morton, H. E. Synthesis of N-(tert-butoxycarbonyl)-3-(4-thiazoyl)-L-alanine. Synth. Commun. 1990, 20, 3507-3517
68. Luly, J. R.; Hsiao, C. N.; BaMaung, N.; Plattner, J. J. A Convenient Stereoselective Synthesis of 1,2,3-Aminodiols from α-Amino Acids. J. Org. Chem. 1988, 53, 6108-6112
69. Sham, H. L.; Stein, H.; Rempel, C. A.; Cohen, J.; Plattner, J. J. Highly Potent and Specific Inhibitors of Human Renin. FEBS Lett. 1987, 220, 299-301
70. Bolis, G.; Fung, A. K. L.; Greer, J.; Kleinert, J. D.; Marcotte, P. A.; Perun, T. J.; Plattner, J. J.; Stein, H. H. Renin Inhibitors. Dipeptide Analogues of Angiotensinogen Incorporating Transition-State, Nonpeptidic Replacements at the Scissile Bond. J. Med. Chem. 1987, 30, 1729-1737
71. Bock, M. G.; DiPardo, R. M.; Evans, B. E.; Rittle, K. E.; Boger, J.; Poe, M.; LaMont, B. I.; Lynch, R. J.; Ulm, E. H.; Vlasuk, G. P.; Greenlee, W. J.; Veber, D. F. Renin Inhibitors. Statine-Containing Tetrapeptides with Varied Hydrophobic Carboxy Termini. J. Med. Chem. 1987, 30, 1853-1857
72. Williams, P. D.; Perlow, D. S.; Payne, L. S.; Holloway, M. K.; Siegl, P. K. S.; Schorn, T. W.; Lynch, R. J.; Doyle, J. J.; Strouse, J. F.; Vlasuk, G. P.; Hoogsteen, K.; Springer, J. P.; Bush, B. L.; Halgren, T. A.; Richards, A. D.; Kay, J.; Veber, D. F. Renin Inhibitors Containing Conformationally Restricted P4-Py Dipeptide Mimics. J. Med. Chem. 1991, 34, 887-900
73. Hutchins, C.; Greer, J. Comparative Modeling of Proteins in the Design of Novel Renin Inhibitors. Crit. Rev. Biochem. Mol. Biol, 1991, 26, 77-127
74. Still, W. C.; Kahn, M.; Mitra, A. Rapid Chromatographic Technique for Preparative Separations with Moderate Resolution. J. Org. Chem. 1978, 43, 2923-2925