2752
L. Zhang et al. / Bioorg. Med. Chem. Lett. 22 (2012) 2748–2752
10. Webster, S. P.; Pallin, T. D. Expert Opin. Ther. Pat. 2007, 17, 1407.
11. Hughes, K. A.; Webster, S. P.; Walker, B. R. Expert Opin. Investig. Drugs 2008, 17,
481.
12. Boyle, C. D.; Kowalski, T. J. Expert Opin. Ther. Pat. 2009, 19, 801.
13. Rosenstock, J.; Banarer, S.; Fonseca, V. A.; Inzucchi, S. E.; Sun, W.; Yao, W.;
Hollis, G.; Flores, R.; Levy, R.; Williams, W. V.; Seckl, J. R.; Huber, R. Diabetes
Care 2010, 33, 1516.
identified as a highly advanced lead and further optimization of its
PK profile and selectivity toward 11b-HSD2 is currently under
progress.
Acknowledgment
14. Feig, P. U.; Shah, S.; Hermanowski-Vosatka, A.; Plotkin, D.; Springer, M. S.;
Donahue, S.; Thach, C.; Klein, E. J.; Lai, E.; Kaufman, K. D. Diabetes Obes. Metab.
2011, 13, 498.
15. Zhang, X.; Zhou, Z.; Yang, H.; Chen, J.; Feng, Y.; Du, L.; Leng, Y.; Shen, J. Bioorg.
Med. Chem. Lett. 2009, 19, 4455.
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (30901838).
16. Zhang, X.; Zhou, Y.; Shen, Y.; Du, L.; Chen, J.; Leng, Y.; Shen, J. Acta Pharmacol.
Sin. 2009, 30, 1344.
Supplementary data
17. For general procedures and characterization data, see the Supplementary data.
18. Mundt, S.; Solly, K.; Thieringer, R.; Hermanowski-Vosatka, A. Assay Drug Dev.
Technol. 2005, 3, 367.
19. Wang, H.; Ruan, Z.; Li, J. J.; Simpkins, L. M.; Smirk, R. A.; Wu, S. C.; Hutchins, R.
D.; Nirschl, D. S.; Van Kirk, K.; Cooper, C. B.; Sutton, J. C.; Ma, Z.; Golla, R.;
Seethala, R.; Salyan, M. E. K.; Nayeem, A.; Krystek, S. R., Jr.; Sheriff, S.; Camac, D.
M.; Morin, P. E.; Carpenter, B.; Robl, J. A.; Zahler, R.; Gordon, D. A.; Hamann, L.
G. Bioorg. Med. Chem. Lett. 2008, 18, 3168.
20. Barf, T.; Vallgårda, J.; Emond, R.; Häggström, C.; Kurz, G.; Nygren, A.; Larwood,
V.; Mosialou, E.; Axelsson, K.; Olsson, R.; Engblom, L.; Edling, N.; Rönquist-Nii,
Y.; Öhman, B.; Alberts, P.; Abrahmsén, L. J. Med. Chem. 2002, 45, 3813.
21. Leeson, P. D.; Springthorpe, B. Nat. Rev. Drug Disc. 2007, 6, 881.
22. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Adv. Drug Delivery Rev.
1997, 23, 3.
23. Christopher, A. L. Drug Discovery Today: Technol. 2004, 1, 337.
24. ClogP calculation based on Pipeline Pilot Webport.
25. White, P. C.; Mune, T.; Rogerson, F. M.; Kayes, K. M.; Agarwal, A. K. Pediatr. Res.
1997, 41, 25.
Supplementary data associated with this article can be found, in
References and notes
1. Tomlinson, J. W.; Walker, E. A.; Bujalska, I. J.; Draper, N.; Lavery, G. G.; Cooper,
M. S.; Hewison, M.; Stewart, P. M. Endocr. Rev. 2004, 25, 831.
2. Wang, M. Nutr. Metab. 2005, 2, 3.
3. Wang, M. Drug Dev. Res. 2006, 67, 567.
4. Stulnig, T. M.; Waldhäusl, W. Diabetologia 2004, 47, 1.
5. Oppermann, U. C. T.; Persson, B.; Jörnvall, H. Eur. J. Biochem. 1997, 249, 355.
6. Seckl, J. R.; Chapman, K. E. Eur. J. Biochem. 1997, 249, 361.
7. Kotelevtsev, Y.; Holmes, M.; Burchell, A.; Houston, P.; Schmoll, D.; Jamieson, P.;
Best, R.; Brown, R.; Edwards, C.; Seckl, J.; Mullins, J. Proc. Natl. Acad. Sci. U.S.A.
1997, 94, 14924.
8. Masuzaki, H.; Paterson, J.; Shinyama, H.; Morton, N. M.; Mullins, J. J.; Seckl, J. R.;
Flier, J. S. Science 2001, 294, 2166.
9. Masuzaki, H.; Yamamoto, H.; Kenyon, C.; Elmquist, J.; Morton, N.; Paterson, J.;
Shinyama, H.; Sharp, M.; Fleming, S.; Mullins, J.; Seckl, J.; Flier, J. J. Clin. Invest.
2003, 112, 83.