Discovery of aminoheterocycles as potent and brain penetrant prolylcarboxypeptidase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 4, 2012, Pages 1727-1730

  Wu, Zhicai ^a   Yang, Cangming ^a   Graham, Thomas H ^a   Verras, Andreas ^a   Chabin, Renee M ^a   Xu, Suoyu ^a   Tong, Xinchun ^a   Xie, Dan ^a   Lassman, Mike E ^a   Bhatt, Urmi R ^a   Garcia Calvo, Margarita M ^a   Shen, Zhu ^a   Chen, Qing ^a   Bleasby, Kelly ^a   Sinharoy, Ranabir ^a   Hale, Jeffrey J ^a   Tata, James R ^a   Pinto, Shirly ^a   Colletti, Steven L ^a   Shen, Dong Ming ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Aminoheterocycles; Inhibitors; PrCP; Prolylcarboxypeptidase

Indexed keywords

ENZYME INHIBITOR; HETEROCYCLIC COMPOUND; PROLINE CARBOXYPEPTIDASE INHIBITOR; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BRAIN; CONTROLLED STUDY; DRUG ACTIVITY; DRUG PENETRATION; DRUG POTENCY; HUMAN; MOUSE; NONHUMAN; PLASMA; STRUCTURE ACTIVITY RELATION;

MUS;

EID: 84862819431     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.12.098     Document Type: Article

References (21)

1. (a) Yang, H. Y. T.; Erdos, E. G.; Chiang, T. S. Nature 1968, 218, 1224
2. (b) Yang, H. Y. T.; Erdos, E. G.; Chiang, T. S.; Jenssen, T. A.; Rodgers, J. G. Biochem. Pharmcol. 1970, 19, 1201
3. (c) Odya, C. E.; Marinkovic, D. V.; Hammon, K. J.; Stewart, T. A.; Erdos, E. G. J. Biol. Chem. 1978, 253, 5927
4. (d) Skidgel, R. A.; Erdos, E. G. Immun. Rev. 1998, 161, 129.
5. (a) Shariat-Madar, Z.; Mhdi, F.; Schmaier, A. H. J. Biol. Chem. 2002, 277, 17962
6. (b) Moreira, C. R.; Schmaier, A. H.; Mahdi, F.; da Motta, G.; Nader, H. B.; Shariat-Madar, Z. FEBS Lett. 2002, 523, 167
7. (c) Shariat-Madar, Z.; Mhdi, F.; Schmaier, A. H. Blood 2004, 103, 4554.
8. (a) Kumamoto, K.; Stewart, T. A.; Johnson, A. R.; Erdos, E. G. J. Clin. Invest. 1981, 67, 210
9. (b) Skidgel, R. A.; Wickstrom, E.; Kumamoto, K.; Erdos, E. G. Anal. Biochem. 1981, 13, 196.
10. Wallingford, N.; Perround, B.; Gao, Q.; Coppola, A.; Gyengesi, E.; Liu, Z. W.; Gao, X. B.; Diament, A.; Haus, K. A.; Shariat-Madar, Z.; Hahdi, F.; Wardlaw, S. L.; Schmaier, A. H.; Warden, C. H.; Diano, S. J. Clin. Invest. 2009, 119, 2291.
11. (a) Mallela, J.; Yang, J.; Shariat-Madar, Z. Int. J. Biochem. Cell Biol. 2009, 41, 477
12. (b) Wang, L.; Feny, Y.; Zhang, Y.; Zhou, H.; Jiang, S.; Niu, T.; Wei, J. L.; Xu, X.; Xu, X. P.; Wang, X. Am. J. Obstet. Gynecol. 2006, 195, 162.
13. Shariat-Madar, B.; Kolte, D.; Verlangiert, A.; Shariat-Madar, Z. Diabetes, Metab. Syndr. Obes.: Targets Ther. 2010, 3, 67.
14. Diament, A. L.; Warden, C. H. Int. J. Obes. 2004, 28, 199.
15. (a) Zhou, C.; Garcia-Calvo, M.; Pinto, S.; Lombardo, M.; Feng, Z.; Bender, K.; Pryor, K. D.; Bhatt, U. R.; Chabin, R. M.; Geissler, W. M.; Shen, Z.; Tong, X.; Zhang, Z.; Wong, K. K.; Roy, R. S.; Chapman, K. T.; Yang, L.; Xiong, Y. J. Med. Chem. 2010, 53, 7251
16. (b) Shen, H. C.; Ding, F.-X.; Zhou, C.; Xiong, Y.; Verras, A.; Chabin, R. M.; Xu, S.; Tong, X.; Xie, D.; Lassman, M. E.; Bhatt, U. R.; Garcia-Calvo, M.; Geissler, W. M.; Shen, Z.; Chen, D.; Sinha, R. R.; Hale, J. J.; Tata, J. R.; Pinto, S.; Shen, D.; Colletti, S. L. Bioorg. Med. Chem. Lett. 2011, 21, 1299
17. (c) Graham, T.; Shen, H. C; Liu, W.; Xiong, Y.; Verras, A.; Bleasby, K.; Bhatt, U. R.; Chabin, R. M.; Chen, D.; Chen, Q.; Garcia-Calvo, M.; Geissler, W. M.; He, H.; Lassman, M. E.; Shen, Z.; Tong, X.; Xie, D.; Xu, S.; Colletti, S. L.; Hale, J.; Tata, J. R.; Pinto, S.; Shen, D. Bioorg. Med. Chem. Lett. 2012, 22, 659.
18. (a) Seelig, A. Eur. J. Biochem. 1998, 251, 252
19. (b) Gatlik-Landwojtowicz, E.; Aanismaa, P.; Seelig, A. Biochemistry 2006, 45, 3020
20. (c) Turunen, B. J.; Ge, H.; Oyetunji, J.; Desino, K. E.; Vasandani, V.; Guthe, S.; Himes, R. H.; Audus, K. L.; Seelig, A.; Georg, G. I. Bioorg. Med. Chem. Lett. 2008, 18, 5971
21. (d) Lawrence, D. S.; Copper, J. E.; Smith, C. D. J. Med. Chem. 2001, 44, 594.