Synthesis and biological evaluation of bicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 12, 2010, Pages 3521-3525

  Cho, Tang Peng ^a   Gang, Lin Zhi ^a   Long, Yang Fang ^a   Yang, Wang ^a   Qian, Wang ^a   Lei, Zhang ^a   Jing, Luo Jing ^a   Ying, Feng ^b   Ke, Yan Pang ^a,b   Ying, Leng ^b   Jun, Feng ^a  

^a Shanghai Hengrui Pharmaceuticals Co Ltd   (China)

^b SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

Bicyclo 3.3.0 octane derivatives; Dipeptidyl peptidase 4; Inhibitors; Oral glucose tolerance tests; Type 2 diabetes

Indexed keywords

ANTIDIABETIC AGENT; BICYCLO[3.3.0]OCTANE DERIVATIVE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLAVUS; GLUCOSE; SAXAGLIPTIN; SITAGLIPTIN; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFICACY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; GLUCOSE BLOOD LEVEL; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST;

ANIMALS; BICYCLO COMPOUNDS; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; GLUCOSE TOLERANCE TEST; MICE; MICE, INBRED STRAINS; OCTANES;

EID: 77954213588     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.04.138     Document Type: Article

References (20)

1. P. Zimmet, K.G.M.M. Alberti, and J. Shaw Nature 414 2001 782
2. J.F. Gautier, S. Fetita, E. Sobngwi, and C. Salaün-Martin Diabetes Metab. 31 2005 233
3. M.A. Nauck, D. Wollschläger, J. Werner, J.J. Holst, C. Ørskov, W. Creutzfeldt, and B. Willms Diabetologia 39 1996 1546
4. M.A. Nauck Acta Diabetol. 3 1998 :117
5. E. Sebokova, A.D. Christ, M. Boehringer, and J. Mizrahi Curr. Top. Med. Chem. 7 2007 547
6. H.B. Rasmussen, S. Branner, F.C. Wiberg, and N. Wagtmann Nat. Struct. Biol. 10 2003 19
7. K.L. Longenecker, K.D. Stewart, D.J. Madar, C.G. Jakob, E.H. Fry, S. Wilk, C.W. Lin, S.J. Ballaron, M.A. Stashko, T.H. Lubben, H. Yong, D. Pireh, Z. Pei, F. Basha, P.E. Wiedeman, T.W. von Geldern, J.M. Trevillyan, and V.S. Stoll Biochemistry 45 2006 7474
8. L. Qiao, C.A. Baumann, C.S. Crysler, N.S. Ninan, M.C. Abad, J.C. Spurlino, R.L. DesJarlais, J. Kervinen, M.P. Neeper, S.S. Bayoumy, R. Williams, I.C. Deckman, M. Dasgupta, R.L. Reed, N.D. Huebert, B.E. Tomczuk, and K.J. Moriarty Bioorg. Med. Chem. Lett. 16 2006 123
9. 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
10. E.B. Villhauer, J.A. Brinkman, G.B. Naderi, B.F. Burkey, B.E. Dunning, K. Prasad, B.L. Mangold, M.E. Russell, and T.E. Hughes J. Med. Chem. 46 2003 2774
11. D.J. Augeri, J.A. Robl, D.A. Betebenner, D.R. Magnin, A. Khanna, J.G. Robertson, A. Wang, L.M. Simpkins, P. Taunk, Q. Huang, S.-P. Han, B. Abboa-Offei, M. Cap, L. Xin, L. Tao, E. Tozzo, G.E. Welzel, D.M. Egan, J. Marcinkeviciene, S.Y. Chang, S.A. Biller, M.S. Kirby, R.A. Parker, and L.G. Hamann J. Med. Chem. 48 2005 5025
12. J.-U. Peters Curr. Top. Med. Chem. 7 2007 579
13. P.C. Tang, Z.G. Lin, Y. Wang, F.L. Yang, Q. Wang, J.H. Fu, L. Zhang, A.S. Gong, J.J. Luo, J. Dai, G.H. She, D.D. Si, and J. Feng Chin. Chem. Lett. 21 2009 253
14. S.H. Bertz, J.M. Cook, A. Gawish, and U. Weiss Org. Synth. Coll. Vol. 7 1990 50
15. The stereoisomeric ratio was determined by gas chromatography (GC) analysis.
16. +.
17. E.B. Villhauer, J.A. Brinkman, G.B. Naderi, B.E. Dunning, B.L. Mangold, M.D. Mone, M.E. Russell, S.C. Weldon, and T.E. Hughes J. Med. Chem. 45 2002 2362
18. 50 values for DPP-4, DPP-8 and DPP-9 were obtained by chemical Luminescent assay using Glo™ Protease Assay Kit (cat. G 8350). For assay conditions, see: Deng, B. C. (Tang, P. C.); Yang, F. L.; Fan, J.; Feng, H.; Wang, Y.; Yang, T. CN101468988A.
19. G.R. Lankas, B. Leiting, S.R. Roy, G.J. Eiermann, M.G. Beconi, T. Biftu, C.-C. Chan, S. Edmondson, W.P. Feeney, H. He, D.E. Ippolito, D. Kim, K.A. Lyons, H.O. Ok, R.A. Patel, A.N. Petrov, K.A. Pryor, X. Qian, L. Reigle, A. Woods, J.K. Wu, D. Zaller, X. Zhang, L. Zhu, A.E. Weber, and N.A. Thornberry Diabetes 54 2005 2988
20. 0-120min) of blood glucose after challenge was calculated by the trapezoidal rule. All date were expressed as the mean ± SEM. The statistical analysis between two groups was performed using an unpaired Student's t test. P <0.05 was considered to be statistically significance.