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

Journal of Medicinal Chemistry

Volumn 41, Issue 9, 1998, Pages 1382-1391

  Hirschmann, Ralph ^a   Hynes Jr , John ^a,c   Cichy Knight, Maria A ^a,d   Van Rijn, Rachel D ^a   Sprengeler, Paul A ^a,e   Spoors, P Grant ^a,d   Shakespeare, William C ^a,f   Pietranico Cole, Sherrie ^a,g   Barbosa, Joseph ^a   Liu, Josephine ^a   Yao, Wenqing ^a,h   Rohrer, Susan ^b   Smith III, Amos B ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d GLAXOSMITHKLINE   (United Kingdom)

^e Arris Pharmaceutical Corporation   (United States)

^f ARIAD PHARMACEUTICALS INC   (United States)

^g HOFFMANN LA ROCHE INC   (United States)

^h DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLO(PROLYLPHENYLALANYL DEXTRO TRYPTOPHYLLYSYLTHREONYLPHENYLALANYL); GLUCOSE; IBUTAMOREN; MANNOSE; RECEPTOR SUBTYPE; SOMATOSTATIN DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CHO CELL; DIASTEREOISOMER; DRUG DESIGN; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PEPTIDE ANALYSIS; RECEPTOR AFFINITY; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL LINE; CHO CELLS; CRICETINAE; ETHERS; GLUCOSIDES; HUMANS; LIGANDS; LYSINE; MICE; MODELS, MOLECULAR; MOLECULAR MIMICRY; MONOSACCHARIDES; PEPTIDE FRAGMENTS; PITUITARY GLAND; RECEPTORS, CELL SURFACE; RECEPTORS, NEUROKININ-1; RECEPTORS, SOMATOSTATIN; SOMATOSTATIN; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 15444347630     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9800346     Document Type: Article

References (85)

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34. Indeed the parenteral peptidal drug octreotide has been approved for clinical use; see: (a) Bauer, W.; Briner, U.; Doepfner, W.; Haller, R.; Huguenin, R.; Marbach, P.; Petcher, T. J.; Pless, J. SMS 201-995: a very potent and selective octapeptide analogue of Somatostatin with prolonged action. Life Sci. 1982, 31, 1133-1140. (b) Lamberts, S. W.; van der Lely, A.-J.; de Herder, W. W.; Hofland, L. J. Octreotide. N. Engl. J. Med. 1996, 334, 246-254. (c) Sassolas, G. Medical therapy with somatostatin analogues for acromegaly. Eur. J. Endocrinol. 1995, 133, 675-677.
35. Indeed the parenteral peptidal drug octreotide has been approved for clinical use; see: (a) Bauer, W.; Briner, U.; Doepfner, W.; Haller, R.; Huguenin, R.; Marbach, P.; Petcher, T. J.; Pless, J. SMS 201-995: a very potent and selective octapeptide analogue of Somatostatin with prolonged action. Life Sci. 1982, 31, 1133-1140. (b) Lamberts, S. W.; van der Lely, A.-J.; de Herder, W. W.; Hofland, L. J. Octreotide. N. Engl. J. Med. 1996, 334, 246-254. (c) Sassolas, G. Medical therapy with somatostatin analogues for acromegaly. Eur. J. Endocrinol. 1995, 133, 675-677.
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40. Freidinger, R., Merck Research Laboratories, private communication.
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42. These results are consistent with the work of Goodman and Veber; see: (a) He, Y.-B.; Huang, Z.; Raynor, K.; Reisine, T.; Goodman, M. Syntheses and Conformations of Somatostatin-Related Cyclic Hexapeptides Incorporating Specific α- and β-Methylated Residues. J. Am. Chem. Soc. 1993, 115, 8066-8072. (b) Huang, Z.; Pröbstl, A.; Spencer, J. R.; Yamazaki, T.; Goodman, M. Cyclic hexapeptide analogs of somatostatin containing bridge modifications. Syntheses and conformational analyses. Int. J. Pept. Protein Res. 1993, 42, 352-365. (c) Huang, Z.; He, Y,-B.; Raynor, K.; Tallent, M.; Reisine, T.; Goodman, M. Main Chain and Side Chain Chiral Methylated Somatostatin Analogs: Syntheses and Conformational Analyses. J. Am. Chem. Soc. 1992, 114, 9390-9401. (d) Brady, S. F.; Paleveda, Jr., W. J.; Arison, B. H.; Saperstein, R.; Brady, E. J.; Raynor, K.; Reisine, T.; Veber, D. F.; Freidinger, R. M. Approaches to Peptidomimetics which serve as Surrogates for the cis Amide Bond: Novel Disulfide-Constrained Bicychc Hexapeptide Analogs of Somatostatin. Tetrahedron 1993, 49, 3449-3466.
43. These results are consistent with the work of Goodman and Veber; see: (a) He, Y.-B.; Huang, Z.; Raynor, K.; Reisine, T.; Goodman, M. Syntheses and Conformations of Somatostatin-Related Cyclic Hexapeptides Incorporating Specific α- and β-Methylated Residues. J. Am. Chem. Soc. 1993, 115, 8066-8072. (b) Huang, Z.; Pröbstl, A.; Spencer, J. R.; Yamazaki, T.; Goodman, M. Cyclic hexapeptide analogs of somatostatin containing bridge modifications. Syntheses and conformational analyses. Int. J. Pept. Protein Res. 1993, 42, 352-365. (c) Huang, Z.; He, Y,-B.; Raynor, K.; Tallent, M.; Reisine, T.; Goodman, M. Main Chain and Side Chain Chiral Methylated Somatostatin Analogs: Syntheses and Conformational Analyses. J. Am. Chem. Soc. 1992, 114, 9390-9401. (d) Brady, S. F.; Paleveda, Jr., W. J.; Arison, B. H.; Saperstein, R.; Brady, E. J.; Raynor, K.; Reisine, T.; Veber, D. F.; Freidinger, R. M. Approaches to Peptidomimetics which serve as Surrogates for the cis Amide Bond: Novel Disulfide-Constrained Bicychc Hexapeptide Analogs of Somatostatin. Tetrahedron 1993, 49, 3449-3466.
44. These results are consistent with the work of Goodman and Veber; see: (a) He, Y.-B.; Huang, Z.; Raynor, K.; Reisine, T.; Goodman, M. Syntheses and Conformations of Somatostatin-Related Cyclic Hexapeptides Incorporating Specific α- and β-Methylated Residues. J. Am. Chem. Soc. 1993, 115, 8066-8072. (b) Huang, Z.; Pröbstl, A.; Spencer, J. R.; Yamazaki, T.; Goodman, M. Cyclic hexapeptide analogs of somatostatin containing bridge modifications. Syntheses and conformational analyses. Int. J. Pept. Protein Res. 1993, 42, 352-365. (c) Huang, Z.; He, Y,-B.; Raynor, K.; Tallent, M.; Reisine, T.; Goodman, M. Main Chain and Side Chain Chiral Methylated Somatostatin Analogs: Syntheses and Conformational Analyses. J. Am. Chem. Soc. 1992, 114, 9390-9401. (d) Brady, S. F.; Paleveda, Jr., W. J.; Arison, B. H.; Saperstein, R.; Brady, E. J.; Raynor, K.; Reisine, T.; Veber, D. F.; Freidinger, R. M. Approaches to Peptidomimetics which serve as Surrogates for the cis Amide Bond: Novel Disulfide-Constrained Bicychc Hexapeptide Analogs of Somatostatin. Tetrahedron 1993, 49, 3449-3466.
45. These results are consistent with the work of Goodman and Veber; see: (a) He, Y.-B.; Huang, Z.; Raynor, K.; Reisine, T.; Goodman, M. Syntheses and Conformations of Somatostatin-Related Cyclic Hexapeptides Incorporating Specific α- and β-Methylated Residues. J. Am. Chem. Soc. 1993, 115, 8066-8072. (b) Huang, Z.; Pröbstl, A.; Spencer, J. R.; Yamazaki, T.; Goodman, M. Cyclic hexapeptide analogs of somatostatin containing bridge modifications. Syntheses and conformational analyses. Int. J. Pept. Protein Res. 1993, 42, 352-365. (c) Huang, Z.; He, Y,-B.; Raynor, K.; Tallent, M.; Reisine, T.; Goodman, M. Main Chain and Side Chain Chiral Methylated Somatostatin Analogs: Syntheses and Conformational Analyses. J. Am. Chem. Soc. 1992, 114, 9390-9401. (d) Brady, S. F.; Paleveda, Jr., W. J.; Arison, B. H.; Saperstein, R.; Brady, E. J.; Raynor, K.; Reisine, T.; Veber, D. F.; Freidinger, R. M. Approaches to Peptidomimetics which serve as Surrogates for the cis Amide Bond: Novel Disulfide-Constrained Bicychc Hexapeptide Analogs of Somatostatin. Tetrahedron 1993, 49, 3449-3466.
46. 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.
47. 3 antagonist cRGDFV albeit with limited success: Nicolaou, K. C.; Trujillo, J. I.; Chibale, K. Design, Synthesis and Biological Evaluation of CarbohydrateBased Mimetics of cRGDFV. Tetrahedron 1997, 53, 8751-8778. See also: Le Diguarher, T.; Boudon, A.; Elwell, C.; Paterson, D. E.; Billington, D. C. Synthesis Of Potential Peptidomimetics Based On Highly Substituted Glucose And Allose Scaffolds. Bioorg. Med. Chem. Lett. 1996, 6, 1983-1988.
48. 3 antagonist cRGDFV albeit with limited success: Nicolaou, K. C.; Trujillo, J. I.; Chibale, K. Design, Synthesis and Biological Evaluation of CarbohydrateBased Mimetics of cRGDFV. Tetrahedron 1997, 53, 8751-8778. See also: Le Diguarher, T.; Boudon, A.; Elwell, C.; Paterson, D. E.; Billington, D. C. Synthesis Of Potential Peptidomimetics Based On Highly Substituted Glucose And Allose Scaffolds. Bioorg. Med. Chem. Lett. 1996, 6, 1983-1988.
49. 3 antagonist cRGDFV albeit with limited success: Nicolaou, K. C.; Trujillo, J. I.; Chibale, K. Design, Synthesis and Biological Evaluation of CarbohydrateBased Mimetics of cRGDFV. Tetrahedron 1997, 53, 8751-8778. See also: Le Diguarher, T.; Boudon, A.; Elwell, C.; Paterson, D. E.; Billington, D. C. Synthesis Of Potential Peptidomimetics Based On Highly Substituted Glucose And Allose Scaffolds. Bioorg. Med. Chem. Lett. 1996, 6, 1983-1988.
50. Kessler and collaborators have employed a monosaccharide residue to constrain the β-turn of SRIF in its bioactive conformation: von Roedern, E. G.; Lohof, E.; Hessler, G.; Hoffmann, M.; Kessler, H. Synthesis and Conformational Analysis of Linear and Cyclic Peptides Containing Sugar Amino Acids. J. Am. Chem. Soc. 1996, 118, 10156-10167. Wessel et al. have demonstrated the use of 6-guanadinopyranoses as arginine mimetics for the inhibition of thrombin: Wessel, H. P.; Banner, D.; Gubernator, K.; Hilpert, K.; Müller, K.; Tschopp, T. 6-Guanadinopyranoses: Novel Carbohydrate-Based Peptidomimetics. Angew. Chem., Int. Ed. Engl. 1997, 36, 751-752.
51. Kessler and collaborators have employed a monosaccharide residue to constrain the β-turn of SRIF in its bioactive conformation: von Roedern, E. G.; Lohof, E.; Hessler, G.; Hoffmann, M.; Kessler, H. Synthesis and Conformational Analysis of Linear and Cyclic Peptides Containing Sugar Amino Acids. J. Am. Chem. Soc. 1996, 118, 10156-10167. Wessel et al. have demonstrated the use of 6-guanadinopyranoses as arginine mimetics for the inhibition of thrombin: Wessel, H. P.; Banner, D.; Gubernator, K.; Hilpert, K.; Müller, K.; Tschopp, T. 6-Guanadinopyranoses: Novel Carbohydrate-Based Peptidomimetics. Angew. Chem., Int. Ed. Engl. 1997, 36, 751-752.
52. Mattos, C.; Ringe, D. Multiple Binding Modes. In 3-D QSAR in Drug Design. Theory, Methods and Applications; Kubinyi, H., Ed.; ESCOM: Leiden, 1993; pp 226-254.
53. Similarly, Bäckbro et al. showed that cyclic sulfamides do not bind HIV-1 protease in the same mode as closely related cyclic ureas, and Smith et al. made a similar observation for pyrrolinone based inhibitors and their peptidal counterparts. It is also relevant that Strader et al. showed that a mutant β2 adrenergic receptor in which Asp 113 was replaced by Glu recognizes several β-blockers as partial agonists; see: (a) Bäckbro, K.; Löwgren, S.; Österlund, K.; Atepo, J.; Unge, T.; Kultén, 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. (b) Smith, A. B., III; Hirschmann, R.; Pasternak, A.; Yao, W.; Sprengeler, P. A. An Orally Bioavailable Pyrrolinone Inhibitor of HIV-1 Protease: Computational Analysis and X-Ray Crystal Structure of the Enzyme Complex. J. Med. Chem. 1997, 40, 2440-2444. (c) Strader, C. D.; Candelore, M. R.; Hill, W. S.; Dixon, R. A. F.; Sigal, I. S. A Single Amino Acid Substitution in the β-Adrenergic Receptor Promotes Partial Agonist Activity from Antagonists. J. Biol. Chem. 1989, 264, 16470-16477.
54. Similarly, Bäckbro et al. showed that cyclic sulfamides do not bind HIV-1 protease in the same mode as closely related cyclic ureas, and Smith et al. made a similar observation for pyrrolinone based inhibitors and their peptidal counterparts. It is also relevant that Strader et al. showed that a mutant β2 adrenergic receptor in which Asp 113 was replaced by Glu recognizes several β-blockers as partial agonists; see: (a) Bäckbro, K.; Löwgren, S.; Österlund, K.; Atepo, J.; Unge, T.; Kultén, 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. (b) Smith, A. B., III; Hirschmann, R.; Pasternak, A.; Yao, W.; Sprengeler, P. A. An Orally Bioavailable Pyrrolinone Inhibitor of HIV-1 Protease: Computational Analysis and X-Ray Crystal Structure of the Enzyme Complex. J. Med. Chem. 1997, 40, 2440-2444. (c) Strader, C. D.; Candelore, M. R.; Hill, W. S.; Dixon, R. A. F.; Sigal, I. S. A Single Amino Acid Substitution in the β-Adrenergic Receptor Promotes Partial Agonist Activity from Antagonists. J. Biol. Chem. 1989, 264, 16470-16477.
55. Similarly, Bäckbro et al. showed that cyclic sulfamides do not bind HIV-1 protease in the same mode as closely related cyclic ureas, and Smith et al. made a similar observation for pyrrolinone based inhibitors and their peptidal counterparts. It is also relevant that Strader et al. showed that a mutant β2 adrenergic receptor in which Asp 113 was replaced by Glu recognizes several β-blockers as partial agonists; see: (a) Bäckbro, K.; Löwgren, S.; Österlund, K.; Atepo, J.; Unge, T.; Kultén, 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. (b) Smith, A. B., III; Hirschmann, R.; Pasternak, A.; Yao, W.; Sprengeler, P. A. An Orally Bioavailable Pyrrolinone Inhibitor of HIV-1 Protease: Computational Analysis and X-Ray Crystal Structure of the Enzyme Complex. J. Med. Chem. 1997, 40, 2440-2444. (c) Strader, C. D.; Candelore, M. R.; Hill, W. S.; Dixon, R. A. F.; Sigal, I. S. A Single Amino Acid Substitution in the β-Adrenergic Receptor Promotes Partial Agonist Activity from Antagonists. J. Biol. Chem. 1989, 264, 16470-16477.
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82. 50 of 27 nM at the NK-1 receptor.
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84. 13C NMR spectra were obtained with a Brucker AMX2-500 spectrometer. Chemical shifts are reported in δ values relative to internal chloroform (δ = 7.24 for proton spectra and δ= 77.0 for carbon spectra) or internal methanol (δ 3.30 for proton spectra and δ 49.0 for carbon spectra) Infrared spectra were determined using a Perkin-Elmer model 283B spectrophotometer using polystyrene as an external standard. High-resolution mass spectra were measured on a VG 70/70 Micromass or VG ZAB-E spectrometer. Optical rotations were measured on a Perkin-Elmer model 241 polarimeter. Microanalyses were performed at Robertson Microlit Laboratoires, Madison, NJ, or at the University of Pennsylvania. Somatostatin, leupeptin, aprotinin, and pepstatin were purchased from Sigma. Bacitracin was obtained from Bachem, and radiolabeled somatostatin-14 was purchased from Amersham.
85. Cascieri, M. A.; Ber, E.; Fong, T. M.; Sadowski, S.; Bansal, A.; Swain, C.; Seward, E.; Frances, B.; Bums, D.; Strader, C. D. Characterization of the Binding of a Potent, Selective, Radioio-dinated Antagonist to the Human Neurokinin-1 Receptor. Mol. Pharmacol. 1992, 42, 458-463.