Discovery of cyclic guanidines as potent, orally active, human glucagon receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 23, 2011, Pages 7131-7136

  Sinz, Christopher ^a   Chang, Jiang ^a   Lins, Ashley Rouse ^a   Brady, Ed ^a   Candelore, Mari ^a   Dallas Yang, Qing ^a   Ding, Victor ^a   Jiang, Guoqiang ^a   Lin, Zhen ^a   Mock, Steven ^a   Qureshi, Sajjad ^a   Salituro, Gino ^a   Saperstein, Richard ^a   Shang, Jackie ^a   Szalkowski, Deborah ^a   Tota, Laurie ^a   Vincent, Stella ^a   Wright, Michael ^a   Xu, Shiyao ^a   Yang, Xiaodong ^a   Zhang, Bei ^a   Tata, James ^a   Kim, Ronald ^a   Parmee, Emma ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Antagonist; Diabetes; Glucagon; Guanidine

Indexed keywords

GLUCAGON RECEPTOR; GLUCOSE; GUANIDINE DERIVATIVE; RECEPTOR BLOCKING AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; DEALKYLATION; DIABETES MELLITUS; DRUG RECEPTOR BINDING; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; RAT;

ADMINISTRATION, ORAL; ANIMALS; BLOOD GLUCOSE; CYCLIZATION; DIABETES MELLITUS, TYPE 2; DISEASE MODELS, ANIMAL; DOGS; DRUG DISCOVERY; GUANIDINES; HUMANS; HYPOGLYCEMIC AGENTS; INHIBITORY CONCENTRATION 50; MOLECULAR STRUCTURE; RATS; RECEPTORS, GLUCAGON; STRUCTURE-ACTIVITY RELATIONSHIP;

MURINAE; RODENTIA;

EID: 80255127461     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.09.085     Document Type: Article

References (15)

1. Inhibition of hepatic glucose production as an approach to type 2 diabetes has been reviewed: R. Kurukulasuriya, J.T. Link, Z. Pei, J.J. Rohde, S.J. Richards, A.J. Souers, and B.G. Szczepankiewicz Curr. Med. Chem. 10 2002 99
2. R. Kurukulasuriya, J.T. Link, D. Madar, Z. Pei, S.J. Richards, J.J. Rohde, A.J. Souers, and B.G. Szczepankiewicz Curr. Med. Chem. 10 2002 123
3. For a recent review of glucagon antagonism for type 2 diabetes, see: S. Ali, and D.J. Drucker Am. J. Physiol. Endocrinol. Metab. 296 2009 E415
4. For a review of small molecule glucagon antagonists, see: K.W. Sloop, M.D. Michael, and J.S. Moyers Expert Opin. Ther. Targets 9 2005 593
5. Y. Liang, M.C. Osborne, B.P. Monia, S. Bhanot, W.A. Gaarde, C. Reed, P. She, T.L. Jetton, and K.T. Demarest Diabetes 53 2004 410
6. K.W. Sloop, J.X.-C. Cao, A.M. Siesky, H.Y. Zhang, D.M. Boenmiller, A.L. Cox, S.J. Jacos, J.S. Moyers, R.A. Owens, A.D. Showalter, M.B. Brenner, A. Raap, J. Gromada, B.R. Berridge, D.K.B. Moneteith, N. Porksen, R.A. McKay, B.P. Monia, S. Bhanot, L.M. Watts, and M. Doson J. Clin. Invest. 113 2004 1571
7. Some aspects of this work have recently been presented: Kim, R.; Chang, J.; Lins, A. R; Sinz, C. J.; Beconi, M.; Brady, E. J.; Candelore, M. R.; Ding, V.; Jiang, G.; Lin, Z.; Qureshi, S.; Salituro, G.; Saperstein, R.; Shang, J.; Tota, L.; Wright, M.; Yang, X.; Tata, J.; Zhang, B.; Parmee, E. Abstracts of Papers, 232nd National Meeting of the American Chemical Society: San Francisco, CA, 2006; American Chemical Society: Washington, DC, 2009; MEDI-294
8. R.M. Kim, J. Chang, A.R. Lins, E. Brady, M.R. Candelore, Q. Dallas-Yang, V. Ding, J. Dragovic, S. Iliff, G. Jiang, S. Mock, S. Qureshi, R. Saperstein, D. Szalkowski, C. Tamvakopoulos, L. Tota, M. Wright, X. Yang, J.R. Tata, K. Chapman, B.B. Zhang, and E.R. Parmee Bioorg. Med. Chem. Lett. 18 2008 3701
9. P. Madsen, J.T. Kodra, C. Behrens, E. Nishimura, C.B. Jeppesen, L. Pridal, B. Andersen, L.B. Knudsen, C. Valcare-Aspegren, M. Guldbrandt, I.T. Christensen, A.S. Jørgensen, L. Ynddal, C.L. Brand, M.A. Bagger, and J. Lau J. Med. Chem. 52 2009 2989
10. K.F. Petersen, and J.T. Sullivan Diabetologia 44 2001 2018
11. S.A. Qureshi, M.R. Candelore, D. Xie, X. Yang, L.M. Tota, V.D.-H. Ding, Z. Li, A. Bansal, C. Miller, S. Cohen, G. Jiang, E. Brady, R. Saperstein, J.L. Duffy, J.R. Tata, K.T. Chapman, D.E. Moller, and B. Zhang Diabetes 53 2004 3267
12. L.-L. Shiao, M.A. Cascieri, M. Trumbauer, H. Chen, and K.A. Sullivan Transgenic Res. 8 1999 295
13. Q. Dallas-Yang, X. Shen, M. Strowski, E. Brady, R. Saperstein, R.E. Gibson, D. Szalkowski, M.R. Candelore, J.E. Fenyk-Melody, E.R. Parmee, B.B. Zhang, and G. Jiang Eur. J. Pharmacol. 501 2004 225
14. K.E. Torraca, X. Huang, C.A. Parrish, and S.L. Buchwald J. Am. Chem. Soc. 123 2001 10770
15. 35S]-radiolabeled MK-499 from HEK cells stably expressing hERG: J.J. Lynch Jr., A.A. Wallace, R.F. Stupienski III, E.P. Baskin, C.M. Beare, S.D. Appleby, J.J. Salata, N.K. Jurkiewicz, M.C. Sanguinetti, R.B. Stein, J.R. Gehret, T. Kothestein, D.A. Claremon, J.M. Elliott, J.W. Butcher, D.C. Remy, and J.J. Baldwin J. Pharmacol. Exp. Ther. 269 1994 541