Small-molecule glucagon receptor antagonists

Drugs of the Future

Volumn 27, Issue 10, 2002, Pages 987-993

  Ling, Anthony ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BAY 27 9955; BENZIMIDAZOLE DERIVATIVE; BETA ALANINE UREA; BIPHENYL DERIVATIVE; GLUCAGON RECEPTOR; GLUCOSE; HORMONE RECEPTOR BLOCKING AGENT; HYDRAZIDE DERIVATIVE; IMIDAZOLE DERIVATIVE; MERCAPTOBENZIMIDAZOLE; PYRIDINE DERIVATIVE; PYRROLE DERIVATIVE; PYRROLO[1,2 A]QUINOXALINE; QUINOLINE HYDRAZONE; SMALL MOLECULE GLUCAGON RECEPTOR ANTAGONIST; STYRYLQUINOXALINE; UNCLASSIFIED DRUG;

DIABETES CONTROL; DIABETES MELLITUS; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; GLUCONEOGENESIS; GLUCOSE HOMEOSTASIS; LIVER MICROSOME; PHARMACOPHORE; REVIEW;

EID: 0036820773     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2002.027.10.701362     Document Type: Review

References (32)

1. Unger, R.H. Role of glucagon in the pathogenesis of diabetes: The status of the controversy. Metabolism 1978, 27, 1691-709.
2. Unger, R.H., Orci, L. The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet 1975, 1:14-26.
3. Unger, R.H., Orci, L. Role of glucagon in diabetes. Arch Intern Med 1977, 137:482-91.
4. Azizeh, B.Y., Ahn, J.M., Caspari, R., Shenderovich, M.D., Trivedi, D., Hruby, V.J. The role of phenylalanine at position 6 in glucagon's mechanism of biological action: Multiple replacement analogues of glucagon. J Med Chem 1997, 40:2555-62.
5. 9]glucagon amide, a glucagon antagonist. Peptides 1989, 10:1171-7.
6. Terleckyj, I., Salzig, M., Unson, C., Merrifield, B. The glucagon receptor antagonist ALT3000 lowers fasting hyperglycemia in rat models of diabetes. Diabetes 1996, 45(Suppl. 2): Abst 220A.
7. Brand, C.L., Rolin, B., Jorgensen, P. N., Svendsen, I., Kristensen, J.S., Holst, J.J. Immunoneutralization of endogenous glucagon with monoclonal glucagon antibody normalizes hyperglycemia in moderately streptozotocin-diabetic rats. Diabetologia 1994, 37:985-93.
8. Brand, C.L., Jorgensen, P.N., Svendsen, I., Holst, J.J. Evidence for a major role for glucagon in regulation of plasma glucose in conscious, nondiabetic, and alloxan-induced diabetic rabbits. Diabetes 1996, 45:1076-83.
9. Brand, C.L., Jorgensen, P.N., Knigge, U. et al. Role of glucagon in maintenance of euglycemia in fed and fasted rats. Am J Physiol 1995, 269:E469-77.
10. Whittle, B.A., Skett, P.G. Pharmaceutical compositions and methods for the manufacture thereof. WO 9735598.
11. West, R., Labroo, V., Piggott, J., Smith, R., McKerman, P.A. Glucagon antagonists and methods relating thereto. US 5508304.
12. West, R.R., Labroo, V., Piggott, J.R., Smith, R.A., McKernan, P.A. Method for inhibiting the stimulation of a glucagon-induced response pathway in a warm-blooded animal in need thereof. US 5677334.
13. Spohr, U.D., Malone, M.J., Mantlo, N.B., Zablocki, J.A. Substituted pyrimidinone and pyridone compounds and methods of use. WO 9824780.
14. Ling, A., Plewe, M.B., Truesdale, L.K. et al. Preparation of 3(benzoylamino)propionic acid derivatives as glucagon antagonists/inverse agonists. WO 0069810.
15. Jorgensen, A.S., Kodra, J.T., Madsen, P., Behrens, C., Sams, C., Lau, J. Glucagon antagonists/inverse agonists. WO 0200612.
16. Collins, J.L., Dambek, P.J., Goldstein, S.W., Faraci, W.S. CP99, 711: A non-peptide glucagon receptor antagonist. Bioorg Med Chem Lett 1992, 2:915-8.
17. Guillon, J., Dallemagne, P., Pfeiffer, B. et al. Synthesis of the new pyrrolo[1,2-a] quinoxalines: Potential non-peptide glucagon receptor antagonists. Eur J Med Chem 1998, 33:293-308.
18. Cook, J.H., Doherty, E.M., Ladouceur, G., Livingston, J.N., MacDougall, M.L. Design and synthesis of quinolines as glucagon antagonists. 216th ACS Natl Meet (Aug 23-27, Boston) 1998, Abst MEDI-285.
19. Madsen, P., Knudsen, L.B., Wiberg, F.C., Carr, R.D. Discovery and structure-activity relationship of the first non-peptide competitive human glucagon receptor antagonists. J Med Chem 1998, 41:5150-7.
20. Ling, A., Hong, Y., Gonzalez, J. et al. Identification of alkylidene hydrazides as glucagon receptor antagonists. J Med Chem 2001, 44:3141-9.
21. Ling, A., Plewe, M., Gonzalez, J. et al. Human glucagon receptor antagonists based on alkylidene hydrazides. Bioorg Med Chem Lett 2002, 12:663-6.
22. Lau, J. Gordon Conference, Medicinal Chemistry (Aug 4-9, New London, NH) 2002.
23. Chang, L., Sidler, K.L., Cascieri, M.A. et al. Substituted imidazoles as glucagon receptor antagonists. Biorg Med Chem Lett 2001, 11:2549-53.
24. De Laszlo, S.E., Hacker, C., Li, B. et al. Potent orally absorbed glucagon receptor antagonists. Bioorg Med Chem Lett 1999, 9:641-6.
25. Cascieri, M.A., Koch, G.E., Ber, E. et al. Characterization of a novel, non-peptidyl antagonist of the human glucagon receptor. J Biol Chem 1999, 274:8694-7.
26. Kim, D., Leung, K.P., MacCoss, M. et al. Design and synthesis of pyridyl pyrroles as glucagon receptor antagonists. 217th ACS Natl Meet (March 21-24, Anaheim) 1999, Abst MEDI-067.
27. Ladouceur, G.H., Cook, J.H., Doherty, E.M., Schoen, W.R., MacDougall, M.L., Livingston, J.N. Discovery of 5-hydroxyalkyl4-phenylpridines as a new class of glucagon receptor antagonists. Bioorg Med Chem Lett 2002, 12:461-4.
28. Schmidt, G., Angerbauer, A., Muller-Gliemann, M. et al. Substituted pyridines and biphenyls as anti-hypercholesterinemic, anti-hyperlipoproeinemic and anti-hyperglycemic agents. WO 04528.
29. Livingston, J.N., MacDougall, M., Ladouceur, G., Schoen, W. BAY-27-9955, a novel, non-peptide antagonist of glucagon binding to the glucagon receptor. Diabetes 1999, 48 (Suppl. 1): A199.
30. Bjorge, S., Jones, L., Mays, R., Hilding, H., Brubaker, W. BAY-27-9955: Plasma pharmacokinetics in Sprague-Dawley rats following intravenous and oral administration. Diabetes 1999, 48 (Suppl. 1): A452.
31. Livingston, J.N., Schoen, W.R. Glucagon and glucagon-like peptide-1. Annu Rep Med Chem 1999, 34:189-98.
32. Petersen, K.F., Sullivan J.T. Effects of a novel glucagon receptor antagonist (Bay 27-9955) on glucagon-stimulated glucose production in humans. Diabetologia 2001, 44:2018-24.