Discovery of novel spirocyclic inhibitors of fatty acid amide hydrolase (FAAH). Part 1: Identification of 7-azaspiro[3.5]nonane and 1-oxa-8-azaspiro[4. 5]decane as lead scaffolds

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 21, 2011, Pages 6538-6544

  Meyers, Marvin J ^a,b   Long, Scott A ^a   Pelc, Matthew J ^a   Wang, Jane L ^a   Bowen, Scott J ^a   Walker, Mark C ^a   Schweitzer, Barbara A ^a   Madsen, Heather M ^a   Tenbrink, Ruth E ^a   McDonald, Joseph ^a   Smith, Sarah E ^a   Foltin, Susan ^a   Beidler, David ^a   Thorarensen, Atli ^a,b  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^b SAINT LOUIS UNIVERSITY   (United States)

Author keywords

Endocannabinoid; FAAH; Fatty acid amide hydrolase; Pain

Indexed keywords

1 OXA 8 AZASPIRO[4.5]DECANE; 7 AZASPIRO[3.5]NONANE; FATTY ACID AMIDASE; FATTY ACID AMIDASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG BINDING; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; STRUCTURE ACTIVITY RELATION;

EID: 80054778775     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.08.055     Document Type: Article

References (22)

1. Ahn, K.; McKinney, M. K.; Cravatt, B. F. Chem. Rev. 2008, 108, 1687.
2. Lambert, D. M.; Fowler, C. J. J. Med. Chem. 2005, 48, 5059;
3. Pacher, P.; Batkai, S.; Kunos, G. Pharmacol. Rev. 2006, 58, 389;
4. Di Marzo, V. Nat. Rev. Drug Disc. 2008, 7, 438.
5. Otrubova, K.; Ezzili, C.; Boger, D. L. Bioorg. Med. Chem. Lett. 2011, 21, 4674;
6. Seierstad, M.; Breitenbucher, J. G. J. Med. Chem. 2008, 51, 7327
7. Boger, D. L.; Miyauchi, H.; Du, W.; Hardouin, C.; Fecik, R. A.; Cheng, H.; Hwang, I.; Hedrick, M. P.; Leung, D.; Acevedo, O.; Guimaraes, C. R. W.; Jorgensen, W. L.; Cravatt, B. F. J. Med. Chem. 2005, 48, 1849.
8. Wang, X.; Sarris, K.; Kage, K.; Zhang, D.; Brown, S. P.; Kolasa, T.; Surowy, C.; El Kouhen, O. F.; Muchmore, S. W.; Brioni, J. D.; Stewart, A. O. J. Med. Chem. 2009, 52, 170.
9. Kathuria, S.; Gaetani, S.; Fegley, D.; Valino, F.; Duranti, A.; Tontini, A.; Mor, M.; Tarzia, G.; La Rana, G.; Calignano, A.; Giustino, A.; Tattoli, M.; Palmery, M.; Cuomo, V.; Piomelli, D. Nat. Med. 2003, 9, 76.
10. Matsumoto, T.; Kori, M.; Miyazaki, J.; Kiyota, Y. WO 2006054652A1, 2006.
11. Ahn, K.; Johnson, D. S.; Fitzgerald, L. R.; Liimatta, M.; Arendse, A.; Stevenson, T.; Lund, E. T.; Nugent, R. A.; Nomanbhoy, T. K.; Alexander, J. P.; Cravatt, B. F. Biochemistry 2007, 46, 13019;
12. Mileni, M.; Johnson, D. S.; Wang, Z.; Everdeen, D. S.; Liimatta, M.; Pabst, B.; Bhattacharya, K.; Nugent, R. A.; Kamtekar, S.; Cravatt, B. F.; Ahn, K.; Stevens, R. C. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 12820;
13. Johnson, D. S.; Ahn, K.; Kesten, S.; Lazerwith, S. E.; Song, Y.; Morris, M.; Fay, L.; Gregory, T.; Stiff, C.; Dunbar, J. B.; Liimatta, M.; Beidler, D.; Smith, S.; Nomanbhoy, T. K.; Cravatt, B. F. Bioorg. Med. Chem. Lett. 2009, 19, 2865.
14. Wang, J. L.; Bowen, S. J.; Schweitzer, B. A.; Madsen, H. M.; McDonald, J.; Pelc, M. J.; Tenbrink, R. E.; Beidler, D.; Thorarensen, A. Bioorg. Med. Chem. Lett. 2009, 19, 5970.
15. Johnson, D. S.; Stiff, C.; Lazerwith, S. E.; Kesten, S. R.; Fay, L. K.; Morris, M.; Beidler, D.; Liimatta, M. B.; Smith, S. E.; Dudley, D. T.; Sadagopan, N.; Bhattachar, S. N.; Kesten, S. J.; Nomanbhoy, T. K.; Cravatt, B. F.; Ahn, K. ACS Med. Chem. Lett. 2011, 2, 91.
16. Meyers, M. J.; Long, S. A.; Pelc, M. J.; Wang, J. L.; Bowen, S. J.; Schweitzer, B. A.; Wilcox, M. V.; McDonald, J.; Smith, S. E.; Foltin, S.; Rumsey, J.; Yang, Y.-S.; Walker, M. C.; Kamtekar, S.; Beidler, D.; Thorarensen, A. Bioorg. Med. Chem. Lett. The subsequent manuscript in this issue.
17. Ahn, K.; Johnson, D. S.; Mileni, M.; Beidler, D.; Long, J. Z.; McKinney, M. K.; Weerpana, E.; Sadagopan, N.; Liimatta, M.; Smith, S. E.; Lazerwith, S.; Stiff, C.; Kamtekar, S.; Bhattacharya, K.; Zhang, Y.; Swaney, S.; Becelaere, K. V.; Stevens, R. C.; Cravatt, B. F. Chem. Biol. 2009, 16, 411.
18. Intermediate 12 was prepared as described in Meyers, M. J.; Muizebelt, I.; van Wiltenburg, J.; Brown, D. L.; Thorarensen, A. Org. Lett. 2009, 11, 3523.
19. Intermediate 15 was prepared as described in Meyers, M. J.; Schweitzer, B. A.; Pelc, M.; Wang, J. L.; Long, S. A.; Thorarensen, A. WO2010/049841, 2010.
20. Intermediate 18 was prepared as described in Long, S. A.; Wang, J. L.; Meyers, M. J.; Pelc, M., Schweitzer, B. A.; Thorarensen, A. WO2010/058318, 2010.
21. Cravatt, B. F.; Wright, A. T.; Kozarich, J. W. Annu. Rev. Biochem. 2008, 77, 383
22. Liu, Y.; Patricelli, M. P.; Cravatt, B. F. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 14694.