New fluorinated pyrrolidine and azetidine amides as dipeptidyl peptidase IV inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 21, 2005, Pages 4770-4773

  Hulin, Bernard ^a   Cabral, Shawn ^a   Lopaze, Michael G ^a   Van Volkenburg, Maria A ^a   Andrews, Kim M ^a   Parker, Janice C ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Cyclohexylglycine; Difluoroazetidine; Difluoropyrrolidine; Dipeptidyl peptidase IV; DPP IV; Fluoroazetidine; Tetrafluoropyrrolidine

Indexed keywords

AZETIDINE DERIVATIVE; CYCLOHEXANE DERIVATIVE; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; FLUORINE DERIVATIVE; GLYCINE DERIVATIVE; ORAL ANTIDIABETIC AGENT; PYRROLIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; DRUG ACTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN;

ADENOSINE DEAMINASE; AMIDES; ANIMALS; ANTIGENS, CD26; AZETIDINES; DIABETES MELLITUS, TYPE 2; DISEASE MODELS, ANIMAL; FLUORINE; GLUCOSE TOLERANCE TEST; GLYCOPROTEINS; INHIBITORY CONCENTRATION 50; MICE; PYRROLIDINES; SERINE PROTEINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 25144476018     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.07.026     Document Type: Article

References (34)

1. D.J. Drucker Exp. Opin. Investig. Drugs 12 2003 87
2. K. Augustyns, P. Van der Veken, and A. Haemers Exp. Opin. Ther. Patents 13 2003 499
3. A.E. Weber J. Med. Chem. 47 2004 4135
4. B. Ahren, and O. Schmitz Horm. Metab. Res. 36 2004 867
5. C.F. Deacon Diabetes 53 2004 2181
6. J.J. Holst, and C.F. Deacon Curr. Opin. Pharmacol. 4 2004 589
7. C.H.S. McIntosh, H.-U. Demuth, J.A. Pospisilik, and R. Pederson Regul. Pept. 128 2005 159
8. E.M. Sinclair, and D.J. Drucker Diabetes 12 2005 146
9. T. Mentlein Exp. Opin. Investig. Drugs 14 2005 57
10. E.B. Villhauer, J.A. Brinkman, G.B. Naderi, B.F. Burkey, B.E. Dunning, and K. Prasad J. Med. Chem. 46 2003 2774
11. B. Ahren, N.M. Landin-Olsson, P.-A. Jansson, and M. Svensson J. Clin. Endocrinol. Metab. 89 2004 2078
12. D. Barlocco Curr. Opin. Investig. Drugs 5 2004 1094
13. B. Ahren, D. Mills, R. Gomis, A. Schweizer, and E. Standl Diabetes Care 27 2004 2874
14. Weber, A. E.; Kim, D.; Beconi, M.; Eiermann, G.; Fisher, M.; He, H.; Hickey, G.; Jaspal, S.; Leiting, B.; Lyons, K.; Marsilio, F.; McCann, P.; Moller, D. E.; Patel, R.; Petrov, A.; Pryor, K.; Sinha Roy, R.; Wu, J. K.; Wyvratt, M.; Zhang, B. B.; Thornberry, N. A. Abstract 633-P, American Diabetes Association 64th Scientific Session: Orlando, FL, June 4-8, 2004.
15. D. Kim, L. Wang, M. Beconi, G.J. Eiermann, M.H. Fisher, H. He, G.J. Hickey, J.E. Kowalchick, B. Leiting, K. Lyons, F. Marsilio, M.E. McCann, R.A. Patel, A. Petrov, G. Scapin, S.B. Patel, R.S. Roy, J.K. Wu, M.J. Wyvratt, B.B. Zhang, L. Zhu, N.A. Thornberry, and A.E. Weber J. Med. Chem. 48 2005 141
16. C.F. Deacon, T.E. Hughes, and J.J. Holst Diabetes 47 1998 764
17. B. Ahren, J.J. Holst, H. Martensson, and B. Balkan Eur. J. Pharmacol. 404 2000 239
18. R.A. Pederson, H.A. White, D. Schlenzig, R.P. Pauly, C.H.S. McIntosh, and H.-U. Demuth Diabetes 47 1998 1253
19. K.J.L. Augustyns, A.M. Lambeir, M. Borloo, I. De Meester, I. Vedernikova, G. Vanhoof, D. Hendriks, S. Scharpe, and A. Haemers Eur. J. Med. Chem. 32 1997 301
20. Hulin, B.; Parker, J. C. PCT Int. Appl. WO 2003/101958.
21. C.G. Caldwell, P. Chen, J. He, E.R. Parmee, B. Leiting, F. Marsilio, R.A. Patel, J.K. Wu, G.J. Eiermann, A. Petrov, H. He, K.A. Lyons, N.A. Thornberry, and A.E. Weber Bioorg. Med. Chem. Lett. 14 2004 1265
22. D.R. Magnin, J.A. Robl, R.B. Sulsky, D.J. Augeri, Y. Huang, L.M. Simpkins, P.C. Taunk, D.A. Betebenner, J.G. Robertson, B.E. Abboa-Offei, A. Wang, M. Cap, L. Xin, L. Tao, D.F. Sitkoff, M.F. Malley, J.Z. Gougoutas, A. Khanna, Q. Huang, S.-P. Han, A. Rex, R.A. Parker, and L.G. Hamann J. Med. Chem. 47 2004 2587
23. Hulin, B. U. S. Patent 6,812,350, 2004.
24. See also: Li, W.; Oliver, E., Jr.; Rojas, C.; Lautar, S.; Thomas, B.; Belyakov, S. Abstracts of Papers, 229th National Meeting of the American Chemical Society, San Diego, CA, March 13-18, 2005; American Chemical Society: Washington, DC, 2005; MEDI 207.
25. G. Giardina, G. Dondio, and M. Grugni Synlett 1995 55
26. Carling, W. R.; Mitchinson, A.; Russell, M. G. N.; Street, L. J. PCT Int. Appl. WO 200047582.
27. M.T. Chaudhry, G.A. Powers, R. Stephens, and J.C. Tatlow J. Chem. Soc. 1964 874
28. R.D. Roberts, and T.A. Spencer Tetrahedron Lett. 1978 2557
29. S. Scharpe, I. DeMeester, G. Vanhof, D. Hendriks, M. van Sande, K. Van Camp, and A. Yaron Clin. Chem. 34 1988 2299
30. Y. Cheng, and W.H. Prusoff Biochem. Pharmacol. 22 1973 3099
31. H.B. Rasmussen, S. Branner, F.C. Wiberg, and N. Wagtmann Nat. Struct. Biol. 10 2003 19
32. 20 could play a substantial role in the subtle effects observed here. For a review on fluorine effects in Medicinal Chemistry see: H.-J. Boehm, D. Banner, S. Bendels, M. Kansy, B. Kuhn, K. Mueller, U. Obst-Sander, and M. Stahl ChemBioChem 5 2004 637
33. J.D. Dunitz, and R. Taylor Chem. Eur. J. 3 1997 89
34. F. Hof, D.M. Scofield, B. Schweizer, and F. Diederich Angew. Chem. Int. Ed. 43 2004 5056