Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 7, 2008, Pages 2409-2413

  Edmondson, Scott D ^a   Wei, Lan ^a   Xu, Jinyou ^a   Shang, Jackie ^a   Xu, Shiyao ^a   Pang, Jianmei ^a   Chaudhary, Ashok ^a   Dean, Dennis C ^a   He, Huaibing ^a   Leiting, Barbara ^a   Lyons, Kathryn A ^a   Patel, Reshma A ^a   Patel, Sangita B ^a   Scapin, Giovanna ^a   Wu, Joseph K ^a   Beconi, Maria G ^b   Thornberry, Nancy A ^a   Weber, Ann E ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b ABBOTT LABORATORIES   (United States)

Author keywords

Amide bond bioisostere; Amide bond mimetic; Amide bond mimic; Dipeptidyl peptidase IV; DPP 4; DPP II; Fluoroolefin; Oxadiazole; QPP

Indexed keywords

ALKENE DERIVATIVE; AMIDE; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; DRUG METABOLITE; FLUOROOLEFIN DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHEMICAL BOND; CONTROLLED STUDY; DRUG CLEARANCE; DRUG METABOLISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN TISSUE; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; STEREOCHEMISTRY; X RAY CRYSTALLOGRAPHY;

ALKENES; AMIDES; ANIMALS; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; HYDROCARBONS, FLUORINATED; HYPOGLYCEMIC AGENTS; MICROSOMES, LIVER; MODELS, CHEMICAL; MOLECULAR MIMICRY; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

RATTUS;

EID: 41149089891     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.02.050     Document Type: Article

References (42)

1. Thornberry N.A., and Weber A.E. Curr. Top. Med. Chem. 7 (2007) 557
2. Edmondson, S. D.; Kim, D. Selective dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes: the discovery of JANUVIA™ (sitagliptin). In Methods and Principles in Medicinal Chemistry, Antitargets Vaz, R. J., Klabunde, T. Eds.; Wiley-VCH, 2008; Vol. 38, 401-422.
3. Herman G.A., Stein P.P., Thornberry N.A., and Wagner J.A. Clin. Pharm. Ther. 81 (2007) 761
4. For lead DPP-4 references, see:. Idris I., and Donnelly R. Diab. Obes. Metab. 9 (2007) 153
5. von Geldern T.W., and Trevillyan J.M. Drug Dev. Res. 67 (2006) 627
6. Augustyns K., Van der Veken P., and Haemers A. Expert Opin. Ther. Pat. 15 (2005) 1387
7. For lead GLP-1 references, see:. Holst J.J. Physiol. Rev. 87 (2007) 1409
8. Drucker D.J. Cell Metab. 3 (2006) 153
9. Drucker D.J., and Nauck M.A. The Lancet 368 (2006) 1696
10. During M.J., Cao L., Zuzga D.S., Francis J.S., Fitzsimons H.L., Jiao X., Bland R.J., Klugmann M., Banks W.A., Drucker D.J., and Haile C.N. Nat. Med. 9 (2003) 1173
11. Meece J. Curr. Med. Res. Opin. 23 (2007) 933
12. Ahren B., Landin-Olsson M., Jansson P.-A., Svensson M., Holmes D., and Schweizer A. J. Clin. Endocrin. Metab. 89 (2004) 2078
13. Edmondson S.D., Mastracchio A., Mathvink R.J., He J., Harper B., Park J.-J., Beconi M., Di Salvo J., Eiermann G.J., He H., Leiting B., Leone J.F., Levorse D.A., Lyons K., Patel R.A., Patel S.B., Petrov A., Scapin G., Shang J., Sinha Roy R., Smith A., Wu J.K., Xu S., Zhu B., Thornberry N.A., and Weber A.E. J. Med. Chem. 49 (2006) 3614
14. Xu J., Wei L., Mathvink R.J., Edmondson S.D., Eiermann G.J., He H., Leone J.F., Leiting B., Lyons K.A., Marsilio F., Patel R.A., Patel S.B., Petrov A., Scapin G., Wu J.K., Thornerry N.A., and Weber A.E. Bioorg. Med. Chem. Lett. 16 (2006) 5373
15. For lead references, see:. Legeay J.C., Eynde J.C.V., and Bazureau J.P. Tetrahedron Lett. 48 (2007) 1063
16. Coburn C.A., Stachel S.J., Jones K.G., Steele T.G., Rush D.M., DiMuzio J., Pietrack B.L., Lai M.-T., Huang Q., Lineberger J., Jin L., Munshi S., Holloway M.K., Espeseth A., Simon A., Hazuda D., Graham S.L., and Vacca J.P. Bioorg. Med. Chem. Lett. 16 (2006) 3635
17. Black W.C., Bayly C.I., Davis D.E., Desmarais S., Falgueyret J.-P., Leger S., Li C.S., Masse F., McKay D.J., Palmer J.T., Percival M.D., Robichaud J., Tsou N., and Zamboni R. Bioorg. Med. Chem. Lett. 15 (2005) 4741
18. Venkatesan N., and Kim B.H. Curr. Med. Chem. 9 (2002) 2243
19. Abraham R.J., Ellison S.L.R., Schonholzer P., and Thomas W.A. Tetrahedron 42 (1986) 2101
20. Allmendinger T., Furet P., and Hungerbuhler E. Tetrahedron Lett. 31 (1990) 7297
21. Welch J.T., and Allmendenger T. In: Kazmierski W.M. (Ed). Peptidomimetic Protocols (1999), Humana Press, New Jersey 375-384
22. Allmendenger T., Felder E., and Hungerbuhler E. Tetrahedron Lett. 31 (1990) 7301
23. Boros L., De Corte B., Gimi R.H., Welch J.T., Wu Y., and Handschumacher R.E. Tetrahedron Lett. 35 (1994) 6033
24. Bartlett P.A., and Otake A. J. Org. Chem. 60 (1995) 3107
25. Niida A., Tomita K., Mizumoto M., Tanigaki H., Terada T., Oishi S., Otaka A., Inui K., and Fujii N. Org. Lett. 8 (2006) 613
26. Welch J.T., and Lin J. Tetrahedron 52 (1996) 291
27. Lin J., Toscano P.J., and Welch J.T. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 14020
28. Zhao K., Lim D.S., Funaki T., and Welch J.T. Bioorg. Med. Chem. Lett. 11 (2003) 207
29. Van der Veken P., Kertesz I., Senten K., Haemers A., and Augustyns K. Tetrahedron Lett. 44 (2003) 6231
30. Van der Veken P., Senten K., Kertesz I., De Meester I., Lambeir A.-M., Maes M.-B., Scharpe S., Haemers A., and Augustyns K. J. Med. Chem. 48 (2005) 1768
31. Tang T.P., and Ellman J.A. J. Org. Chem. 67 (2002) 7819
32. Liang G.-B., and Feng D.D. Tetrahedron Lett. 37 (1996) 6627
33. 1H NMR and LC-MS.
34. Suda M. Synthesis 9 (1981) 714
35. 50 determinations for DPP-4 and QPP were carried out as described in:. Leiting B., Pryor K.D., Wu J.K., Marsilio F., Patel R.A., Craik C.S., Ellman J.A., Cummings R.T., and Thornberry N.A. Biochem. J. 371 (2003) 525
36. 50's are an average of n ≥ 2, with standard deviations less than 75% of the average.
37. For a discussion of the relevance of selectivity over DPP8 and DPP9, see:. Lankas G.R., Leiting B., Sinha Roy R., Eiermann G.J., Beconi M.G., Biftu T., Chan C.-C., Edmondson S., Feeney W.P., He H., Ippolito D.E., Kim D., Lyons K.A., Ok H.O., Patel R.A., Petrov A.N., Pryor K.A., Qian X., Reigle L., Woods A., Wu J.K., Zaller D., Zhang X., Zhu L., Weber A.E., and Thornberry N.A. Diabetes 54 (2005) 2988
38. The atomic coordinates for the X-ray structures of DPP-4 in complex with 3 and 31 have been deposited into the RCSB protein data bank under RCSB ID codes rcsb046315 and rscb046317, and under PDB ID codes 3C43 and 3C45, respectively.
39. 50 determinations for hERG was carried out as described in:. Friesen R.W., Ducharme Y., Ball R.G., Blouin M., Boulet L., Cote B., Frenette R., Girard M., Guay D., Huang Z., Jones T.R., Laliberte F., Lynch J.J., Mancini J., Martins E., Masson P., Muise E., Pon D.J., Siegel P.K.S., Styhler A., Tsou N.N., Turner M.J., Young R.N., and Girard Y. J. Med. Chem. 46 (2003) 2017
40. For related work done to identify metabolites on fluoropyrrolidine-derived DPP-4 inhibitors, see:. Xu S., Zhu B., Teffera Y., Pan D.E., Caldwell C.G., Doss G., Stearns R.A., Evans D.C., and Beconi M.G. Drug Metab. Dispos. 33 (2005) 121
41. Evans D.C., Watt A.P., Nicoll-Griffith D.A., and Baillie T.A. Chem. Res. Toxicol. 17 (2004) 3
42. Uetrecht J.P. Chem. Res. Toxicol. 12 (1999) 387