Small molecule glucagon receptor antagonists: A patent review (2011-2014)

Expert Opinion on Therapeutic Patents

Volumn 25, Issue 7, 2015, Pages 819-830

  Filipski, Kevin J ^a  

^a PFIZER INC   (United States)

Author keywords

Diabetes; Glucagon; Glucagon receptor; Glucagon receptor antagonist

Indexed keywords

BAY 27 9955; CYCLIC AMP; GCGR; GLUCAGON RECEPTOR; GLUCAGON RECEPTOR ANTAGONIST; HORMONE RECEPTOR BLOCKING AGENT; LGD 6972; LY 2409021; MK 0893; MK 3577; PF 06291874; PICOLINAMIDE; UNCLASSIFIED DRUG; US 20120202834; WO 2011027849; WO 2011037815; WO 2011119541; WO 2012162407; WO 2012162409; WO 2013014569; ANTIDIABETIC AGENT; GLUCOSE BLOOD LEVEL;

BINDING ASSAY; CHEMICAL ANALYSIS; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG INDUSTRY; DRUG MANUFACTURE; DRUG MECHANISM; DRUG STRUCTURE; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; HUMAN; IC50; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; VASCULAR PATENCY; ANIMAL; ANTAGONISTS AND INHIBITORS; DIABETES MELLITUS, TYPE 2; DRUG DESIGN; DRUG EFFECTS; LIVER; METABOLISM; PATENT;

ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; DRUG DESIGN; HUMANS; HYPOGLYCEMIC AGENTS; LIVER; PATENTS AS TOPIC; RECEPTORS, GLUCAGON;

EID: 84934999360     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2015.1032250     Document Type: Review

References (76)

1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87(1):4-14
2. Kaiser D, Oetjen E. Something old, something new and something very old: drugs for treating type 2 diabetes. Br J Pharmacol 2014;171(12):2940-50
3. Tahrani AA, Bailey CJ, Del Prato S, Barnett AH. Management of type 2 diabetes: new and future developments in treatment. Lancet 2011;378(9786):182-97
4. Estall JL, Drucker DJ. Glucagon and glucagon-like peptide receptors as drug targets. Curr Pharm Des 2006;12(14):1731-50
5. Johnson DG, Goebel CU, Hruby VJ, et al. Hyperglycemia of diabetic rats decreased by a glucagon receptor antagonist. Science 1982;215(4536):1115-16
6. Gysin B, Trivedi D, Johnson DG, Hruby VJ. Design and synthesis of glucagon partial agonists and antagonists. Biochemistry 1986;25(25):8278-84
7. Gelling RW, Du XQ, Dichmann DS, et al. Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice. Proc Natl Acad Sci USA 2003;100(3):1438-43
8. Sorensen H, Winzell MS, Brand CL, et al. Glucagon receptor knockout mice display increased insulin sensitivity and impaired beta-cell function. Diabetes 2006;55(12):3463-9
9. Conarello SL, Jiang G, Mu J, et al. Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia. Diabetologia 2007;50(1):142-50
10. Lee Y, Wang M-Y, Du XQ, et al. Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes 2011;60(2):391-7
11. Vuguin PM, Charron MJ. Novel insight into glucagon receptor action: lessons from knockout and transgenic mouse models. Diabetes Obes Metab 2011;13(Suppl 1):144-50
12. Sorensen H, Brand CL, Neschen S, et al. Immunoneutralization of endogenous glucagon reduces hepatic glucose output and improves long-term glycemic control in diabetic ob/ob mice. Diabetes 2006;55(10):2843-8
13. Brand CL, Rolin B, Jorgensen PN, et al. Immunoneutralization of endogenous glucagon with monoclonal glucagon antibody normalizes hyperglycaemia in moderately streptozotocin-diabetic rats. Diabetologia 1994;37(10):985-93
14. Liang Y, Osborne MC, Monia BP, et al. Reduction in glucagon receptor expression by an antisense oligonucleotide ameliorates diabetic syndrome in db/db mice. Diabetes 2004;53(2):410-17
15. Sloop KW, Cao JX, Siesky AM, et al. Hepatic and glucagon-like peptide-1-mediated reversal of diabetes by glucagon receptor antisense oligonucleotide inhibitors. J Clin Invest 2004;113(11):1571-81
16. Collins JL, Dambek PJ, Goldstein SW, Faraci WS. CP-99, 711: a nonpeptide glucagon receptor antagonist. Bioorg Med Chem Lett 1992;2(9):915-18.
17. Madsen P, Brand CL, Holst JJ, Knudsen B. Advances in non-peptide glucagon receptor antagonists. Curr Pharm Des 1999;5(9):683-91
18. DeMong DE, Miller MW. Glucagon receptor antagonists in development. In: Jones RM, editor. New therapeutic strategies for type 2 diabetes: small molecule approaches. The Royal Society of Chemistry; Cambridge, UK: 2012. p. 429-63
19. DeMong DE, Miller MW, Lachowicz JE. Glucagon receptor antagonists for type II diabetes. Annu Rep Med Chem 2008;43:119-37
20. Ling A. Small-molecule glucagon receptor antagonists. Drugs Future 2002;27(10):987-93
21. Ling AL, Wasserman JI. Approaches to glucagon receptor antagonists. Expert Opin Ther Pat 2003;13(1):15-22
22. Kurukulasuriya R, Link J. Progress towards glucagon receptor antagonist therapy for type 2 diabetes. Expert Opin Ther Pat 2005;15(12):1739-49
23. Shen DM, Lin S, Parmee ER. A survey of small molecule glucagon receptor antagonists from recent patents (2006-2010). Expert Opin Ther Pat 2011;21(8):1211-40
24. Dainippon Sumitomo Pharma Co., Ltd. Preparation of 3-substituted-2-furancarboxylic acid hydrazide derivatives as glucagon receptor antagonists. WO2011007722; 2011
25. Dainippon Sumitomo Pharma Co., Ltd. Preparation of 3-(4-aminophenyl)-2-furancarboxylic acid hydrazide derivatives as glucagon receptor antagonists and pharmaceutically acceptable salts thereof. WO2010131669; 2010
26. Hasegawa F, Niidome K, Migihashi C, et al. Discovery of furan-2-carbohydrazides as orally active glucagon receptor antagonists. Bioorg Med Chem Lett 2014;24(17):4266-70
27. Lau J, Behrens C, Sidelmann UG, et al. New beta-alanine derivatives are orally available glucagon receptor antagonists. J Med Chem 2007;50(1):113-28
28. Janssen Pharmaceutica NV. Preparation of biphenylcarboxamidopropanoic acid derivatives for use as glucagon receptor antagonists. WO2012162409; 2012
29. Janssen Pharmaceutica NV. Preparation of picolinamido propanoic acid derivatives useful as glucagon receptor antagonists. WO2012162407; 2012
30. Janssen Pharmaceutica NV. Picolinamido-propanoic acid derivatives useful as glucagon receptor antagonists. US8748624; 2014
31. Madsen P, Ling A, Plewe M, et al. Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent and orally available 3-cyano-4-hydroxybenzoic acid [1-(2, 3, 5, 6-tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide. J Med Chem 2002;45(26):5755-75
32. Lau J, Behrens C, Sidelmann UG, et al. New beta-alanine derivatives are orally available glucagon receptor antagonists. J Med Chem 2007;50(1):113-28
33. Pfizer, Inc. Preparation of heterocyclecontaining compounds as glucagon receptor modulators for therapy. WO2012085745; 2012
34. Pfizer, Inc. Glucagon receptor modulators. US8809342; 2014
35. Pfizer, Inc. Preparation of 3-[4-(heterocyclyl-substituted)-benzamido] propanoic acids as glucagon receptor modulators. US20120202834; 2012.
36. Guzman-Perez A, Pfefferkorn JA, Lee EC, et al. The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus. Bioorg Med Chem Lett 2013;23(10):3051-8
37. Pfizer, Inc. Glucagon receptor modulators. US8859591; 2014
38. Pfizer, Inc. Glucagon receptor modulators. US8507533; 2013
39. Pfizer, Inc. Preparation of quinolinyl glucagon receptor modulators. WO2013014569; 2013
40. Schering Corp. Pyrrolidines as glucagon receptor antagonists and their preparation and use for the treatment and prevention of type 2 diabetes and related diseases. WO2011037815; 2011
41. Merck & Co., Inc. Processes for preparation of a substituted pyrazole useful as a glucagon receptor antagonist. WO2007015999; 2007
42. Merck Sharp & Dohme Corp. Pyrrolidines as glucagon receptor antagonists, compositions, and methods for their use. US8735604; 2014
43. Schering Corp. Spiro-imidazolone derivatives as glucagon receptor antagonists and their preparation and use for the treatment and prevention of type 2 diabetes and related conditions. WO2011119541; 2011
44. Schering Corp. Spiro-imidazolone derivatives as glucagon receptor antagonists and their preparation and use for treatment and prevention of type 2 diabetes and related conditions. WO2011119559; 2011
45. Schering Corp. Preparation of spiroimidazolone derivatives as glucagon receptor antagonists for treatment of diabetes. WO2010039789; 2010
46. Takeda Pharmaceutical Co. Ltd. Preparation of heterocyclic compounds as glucagon antagonists. WO2011027849; 2011
47. Takeda Pharmaceutical Co. Ltd. Preparation of (heterocyclylmethyl)amine compounds as glucagon receptor antagonists. WO2009110520; 2009
48. Takeda Pharmaceutical Co. Ltd. Preparation of aromatic ring compounds as glucagon antagonists. WO2013147026; 2013
49. Petersen KF, Sullivan JT. Effects of a novel glucagon receptor antagonist (Bay 27-9955) on glucagon-stimulated glucose production in humans. Diabetologia 2001;44(11):2018-24.
50. Xiong Y, Guo J, Candelore MR, et al. Discovery of a novel glucagon receptor antagonist N-[(4-{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-beta-alanine (MK-0893) for the treatment of type II diabetes. J Med Chem 2012;55(13):6137-48.
51. Engel SS, Reitman ML, Xu L, et al. Glycemic and lipid effects of the shortacting glucagon receptor antagonist MK-3577 in patients with type 2 diabetes. Diabetes 2012;61(Suppl 1):A266.
52. Peng JZ, Denney WS, Musser BJ, et al. A semi-mechanistic model for the effects of a novel glucagon receptor antagonist on glucagon and the interaction between glucose, glucagon, and insulin applied to adaptive phase II design. AAPS J 2014;16(6):1259-70
53. Chung JYL, Steinhuebel D, Krska SW, et al. Asymmetric synthesis of a glucagon receptor antagonist via friedel-crafts alkylation of indole with chiral alphaphenyl benzyl cation. Org Process Res Dev 2012;16(11):1832-45
54. Merck Sharp & Dohme Corp. Preparation and crystalline polymorphic forms of an antidiabetic indole betaalanine derivative. WO2010080971; 2010.
55. Merck pipeline as of November 4, 2009. Available from: www.merck.com/research/pipeline/Merck%20October% 202009%20Combined%20Pipeline.pdf [Last accessed 7 January 2015]
56. Merck pipeline as of February 12, 2010. Available from: www.merck.com/research/pipeline/pipeline-feb-2010.pdf [Last accessed 7 January 2015]
57. Merck pipeline as of April 30, 2010. Available from: www.merck.com/research/pipeline/pipeline-may-2010.pdf [Last accessed 7 January 2015]
58. Merck pipeline as of July 30, 2010. Available from: www.merck.com/research/pipeline/pipeline-july-2010.pdf [Last accessed 7 January 2015]
59. Kazda C, Headlee S, Ding Y, et al. The glucagon receptor antagonist LY2409021 significantly lowers HbA1c and is well tolerated in patients with T2DM: a 24 week phase 2 study. Diabetes 2013;62(Suppl 1):A29.
60. DeFronzo RA, Triplitt CL, Abdul-Ghani M, Cersosimo E. Novel agents for the treatment of type 2 diabetes. Diabetes Spectr 2014;27(2):100-12
61. Lilly clinical development pipeline as of January 23, 2015. Available from: http://www.lilly.com/SiteCollectionDocuments/Pipeline/Clinical%20Development% 20Pipeline/index.html#PhaseII [Last accessed 13 March 2015]
62. Pfizer pipeline as of November 6, 2014. Available from: www.pfizer.com/research/science-and-technology/product-pipeline [Last accessed 7 January 2015]
63. Pfizer pipeline as of February 27, 2015. Available from: http://www.pfizer.com/research/science-and-technology/product-pipeline [Last accessed 13 March 2015]
64. Pfizer phase 2 clinical trial. Available from: https://clinicaltrials.gov/ct2/show/NCT02175121?term=PF-06291874&rank=3 [Last accessed 13 March 2015]
65. Ligand diabetes portfolio. Available from: www.ligand.com/diabetes-portfolio [Last accessed 7 January 2015]
66. Ligand single dose clinical trial. Available from: www.clinicaltrials.gov/ct2/results? term=NCT01919684&Search=Search [Last accessed 7 January 2015]
67. Vajda EG, Plotkin DJ, Logan D, et al. Pharmacokinetics of the glucagon receptor antagonist LGD-6972. Diabetes 2014;63(Suppl 1):A290
68. Ligand phase 1 escalating dose. Available from: www.clinicaltrials.gov/ct2/results? term=NCT02250222&Search=Search [Last accessed 7 January 2015]
69. Ligand-Metabasis merger press release. Available from: investor.ligand.com/Investors/News-and-Events/Press-Releases/Press-Release-Details/2009/Ligand-to-Acquire-Metabasis-for-Cashand-Contingent-Value-Rights/default.aspx [Last accessed 7 January 2015]
70. Isis description of GCGRRx. Available from: www.isispharm.com/Pipeline/Therapeutic-Areas/Metabolic-Disease. htm#ISIS-GCGR [Last accessed 7 January 2015]
71. Isis Pharmaceuticals pipeline. Available from: www.isispharm.com/Pipeline/index. htm [Last accessed 7 January 2015]
72. Isis press release June 16, 2014. Available from: ir.isispharm.com/phoenix.zhtml? c=222170&p=irolnewsArticle& ID=1939938 [Last accessed 7 January 2015].
73. Mu J, Qureshi SA, Brady EJ, et al. Anti-diabetic efficacy and impact on amino acid metabolism of GRA1, a novel small-molecule glucagon receptor antagonist. PLoS ONE 2012;7(11):e49572
74. Han S, Akiyama TE, Previs SF, et al. Effects of small interfering RNAmediated hepatic glucagon receptor inhibition on lipid metabolism in db/db mice. J Lipid Res 2013;54(10):2615-22
75. Siu FY, He M, de Graaf C, et al. Structure of the human glucagon class B G-protein-coupled receptor. Nature 2013;499(7459):444-9
76. Grover S, Dhanjal JK, Goyal S, et al. Computational identification of novel natural inhibitors of glucagon receptor for checking type II diabetes mellitus. BMC Bioinformatics 2014;15(Suppl 16):S13