Design and synthesis of conformationally constrained tri-substituted ureas as potent antagonists of the human glucagon receptor

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 3, 2007, Pages 587-592

  Liang, Rui ^a   Abrardo, Lauren ^a   Brady, Edward J ^a   Candelore, Mari Rios ^a   Ding, Victor ^a   Saperstein, Richard ^a   Tota, Laurie M ^a   Wright, Michael ^a   Mock, Steve ^a   Tamvakopolous, Constantin ^a   Tong, Sharon ^a   Zheng, Song ^a   Zhang, Bei B ^a   Tata, James R ^a   Parmee, Emma R ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Diabetes; Glucagon; Glucagon receptor; Glucagon receptor antagonist; Glucose; Hyperglycemia

Indexed keywords

GLUCAGON RECEPTOR; HORMONE RECEPTOR BLOCKING AGENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG SYNTHESIS; EVALUATION; GLUCOSE BLOOD LEVEL; IC 50; LIPID DIET; MOUSE; NONHUMAN; RECEPTOR BINDING; SUBSTITUTION REACTION;

ANIMALS; BLOOD GLUCOSE; CHO CELLS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CRICETINAE; CRICETULUS; CYCLIC AMP; DIETARY FATS; DRUG DESIGN; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON; HALF-LIFE; HUMANS; HYPERGLYCEMIA; INDICATORS AND REAGENTS; MICE; MICE, TRANSGENIC; MOLECULAR CONFORMATION; RECEPTORS, GLUCAGON; UREA;

MUS; MUS MUSCULUS;

EID: 33846225690     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.11.014     Document Type: Article

References (32)

1. Zhang B.B., and Moller D.B. Curr. Opin. Chem. Biol. 4 (2000) 461
2. Jiang G., and Zhang B.B. Am. J. Physiol. 284 (2003) E671
3. Sloop K.W., and Michael M.D. Drugs Future 29 (2004) 835
4. Unger R.H. Metabolism 27 (1978) 1691
5. Brand C.L., Rolin B., Jorgensen P.N., Svendsen I., Kristensen J.S., and Holst J.J. Diabetologia 37 (1994) 985
6. Brand C.L., Jorgensen P.N., Knigge U., Warberg J., Svendsen I., Kristensen J.S., and Holst J.J. Am. J. Physiol. 269 (1995) E469
7. Brand C.L., Jorgensen P.N., Svendsen I., and Holst J.J. Diabetes 45 (1996) 1076
8. Brand C.L., Hansen B., Groneman S., Boysen M., and Holst J.J. Diabetes 49 (2000) A81
9. Liang Y., Osborne M.C., Monia B.P., Bhanot S., Gaarde W.A., Reed C., She P., Jetton T.L., and Demarest K.T. Diabetes 53 (2004) 410
10. Sloop K.W., Cao J.X.-C., Siesky A.M., Zhang H.Y., Bodenmiller D.M., Cox A.L., Jacobs S.J., Moyers J.S., Owens R.A., Showalter A.D., Brenner M.B., Raap A., Gromada J., Berridge B.R., Monteith D.K.B., Porksen N., McKay R.A., Monia B.P., Bhanot S., Watts L.M., and Michael M.D. J. Clin. Invest. 113 (2004) 1571
11. Petersen K.F., and Sullivan J.T. Diabetologia 44 (2001) 2018
12. Ling A. Drugs Future 27 (2002) 987
13. Ling A.L., and Wasserman J.I. Expert Opin. Ther. Patents 13 (2003) 15
14. Kurukulasuriya R., and Link J.T. Expert Opin. Ther. Patents 15 (2005) 1739
15. Madsen P., Knudsen L.B., Wiberg F.C., and Carr R.D. J. Med. Chem. 41 (1998) 5150
16. De Laszlo S.E., Hacker C., Li B., Kim D., MacCoss M., Mantlo N., Pivnichny J.V., Colwell L., Koch G.E., Cascieri M.A., and Hagmann W.K. Bioorg. Med. Chem. Lett. 9 (1999) 641
17. Chang L.L., Sidler K.L., Cascieri M.A., De Laszlo S., Koch G., Li B., MacCoss M., Mantlo N., O'Keefe S., Pang M., Rolando A., and Hagmann W.K. Bioorg. Med. Chem. Lett. 11 (2001) 2549
18. Ladouceur G.H., Cook J.H., Hertzog D.L., Jones J.H., Hundertmark T., Korpusik M., Lease T.G., Livingston J.N., MacDougall M.L., Osterhout M.H., Phelan K., Romero R.H., Schoen W.R., Shao C., and Smith R.A. Bioorg. Med. Chem. Lett. 12 (2002) 3421
19. Madsen P., Ling A., Plewe M., Sams C.K., Knudsen L.B., Sidelmann U.G., Ynddal L., Brand C.L., Andersen B., Murphy D., Teng M., Truesdale L., Kiel D., May J., Kuki A., Shi S., Johnson M.D., Teston K.A., Feng J., Lakis J., Anderes K., Gregor V., and Lau J. J. Med. Chem. 45 (2002) 5755
20. Kurukulasuriya R., Sorensen B.K., Link J.T., Patel J.R., Jae H.-S., Winn M.X., Rohde J.R., Grihalde N.D., Lin C.W., Ogiela C.A., Adler A.L., and Collins C.A. Bioorg. Med. Chem. Lett. 14 (2004) 2047
21. Ling, A.; Plewe, M. B.; Truesdale, L. K.; Lau, J.; Madsen, P.; Sams, C.; Behrens, C.; Vagner, J.; Christensen, I. T.; Lundt, B. F.; Sidelmann, U. G.; Thøgersen, H. WO 00/69810, 2000.
22. Jørgensen, A. S.; Christensen, I. T.; Kodra, J. T.; Madsen, P.; Behrens, C.; Sams, C.; Lau, J. WO 02/00612 A1, 2002.
23. Qureshi S.A., Candelore M.R., Xie D., Yang X., Tota L.M., Ding V.D.-H., Li Z., Bansal A., Miller C., Cohen S.M., Jiang G., Brady E., Saperstein R., Duffy J.L., Tata J.R., Chapman K.T., Moller D.E., and Zhang B.B. Diabetes 53 (2004) 3267
24. Shen D.-M., Zhang F., Brady E.J., Candelore M.R., Yang Q.D., Ding V.D.-H., Dragovic J., Feeney W.P., Jiang G., McCann P.E., Mock S., Qureshi S.A., Saperstein R., Shen X., Tamvakopoulos C., Tong X., Tota L.M., Wright M.J., Yang X., Zheng S., Chapman K.T., Zhang B.B., Tata J.R., and Parmee E.R. Bioorg. Med. Chem. Lett. 15 (2005) 4564
25. The following patent also disclosed structures such as these. Kurukulasuriya, R.; Link, J. T.; Patel, J. R.; Sorensen, B. K. US 2004/0209928 A1, 2004.
26. 6-Hydroxy-1-chromanone 13 was readily prepared in 2 steps:. Koch K., and Biggers M.S. J. Org. Chem. 59 (1994) 1216
27. Mayo K.E., Miller L.J., Bataille D., Dalle S., Goke B., Thorens B., and Drucker D.J. Pharmacol. Rev. 55 (2003) 167
28. 3O-aniline or 4-cyclohexyl-aniline was affected by decaborane.
29. Compounds 25-27 were prepared through acylation of intermediate 9, which was resolved on chiral HPLC as the t-BOC-protected carbamate.
30. +) was high (>1000-fold).
31. Dallas-Yang Q., Shen X., Strowski M., Brady E., Saperstein R., Gibson R.E., Szalkowski D., Qureshi S.A., Candelore M.R., Fenyk-Melody J.E., Parmee E.R., Zhang B.B., and Jiang G. Eur. J. Pharmacol. 501 (2004) 225
32. Brady E.J., McCann P., Saperstein R., Candelore M., Jiang G., Liu F., Woods J., Zycband E., Zhang F., Shen D.-M., Parmee E.R., and Zhang B.B. Diabetes V55 (2006) P.A141