Synthesis, SAR study, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase (FAAH) inhibitors

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 1, 2013, Pages 28-41

  Kono, Mitsunori ^a   Matsumoto, Takahiro ^a   Kawamura, Toru ^a   Nishimura, Atsushi ^a   Kiyota, Yoshihiro ^a   Oki, Hideyuki ^a   Miyazaki, Junichi ^a   Igaki, Shigeru ^a   Behnke, Craig A ^b   Shimojo, Masato ^a   Kori, Masakuni ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b Takeda San Diego Inc   (United States)

Author keywords

Arachidonoylethanolamide; Fatty acid amide hydrolase inhibitors; Piperazine ureas; Thiadiazole derivatives; Thiazole derivatives

Indexed keywords

1 (2 FLUOROPHENYL) 2 THIOCYANATOETHANONE; 1 (2,4 DIFLUOROPHENYL) 2 THIOCYANATOETHANONE; 1 (3 FLUOROPHENYL) 2 THIOCYANATOETHANONE; 1 (4 FLUOROPHENYL) 2 THIOCYANATOETHANONE; 1 PHENYL 2 THIOCYANATOETHANONE; 2 BROMO 4 PHENYLTHIAZOLE; 3 PHENYL 5 (PIPERAZIN 1 YL) 1,2,4 THIADIAZOLE; 4 (2 FLUOROPHENYL) 2 (PIPERAZIN 1 YL)THIAZOLE; 4 (3 FLUOROPHENYL) 2 (PIPERAZIN 1 YL)THIAZOLE; 4 PHENYL 2 (PIPERAZIN 1 YL)THIAZOLE; 5 CHLORO 3 (2 FLUOROPHENYL) 1,2,4 THIADIAZOLE; 5 CHLORO 3 (3 FLUOROPHENYL) 1,2,4 THIADIAZOLE; 5 CHLORO 3 (4 FLUOROPHENYL) 1,2,4 THIADIAZOLE; 5 CHLORO 3 PHENYL 1,2,4 THIDIAZOLE; ETHYL 4 (4 PHENYLTHIOPHEN 2 YL)PIPERAZINE 1 CARBOXYLATE; FATTY ACID AMIDASE; FATTY ACID AMIDASE INHIBITOR; N (3,4 DIMETHYLISOXAZOL 5 YL) 4 [3 (3 FLUOROPHENYL) 1,2,4 THIADIAZOL 5 YL]PIPERAZINE 1 CARBOXAMIDE; N (3,4 DIMETHYLISOXAZOL 5 YL) 4 [3 (4 FLUOROPHENYL) 1,2,4 THIADIAZOL 5 YL]PIPERAZINE 1 CARBOXAMIDE; N (BENZO[D]ISOXAZOL 3 YL) 4 (3 PHENYL 1,2,4 OXADIAZOL 5 YL)PIPERAZINE 1 CARBOXAMIDE; N (BENZO[D]ISOXAZOL 3 YL) 4 (4 PHENYLTHIAZOL 2 YL)PIPERIDINE 1 CARBOXAMIDE; PIPERAZINE UREA DERIVATIVE; TERT BUTYL 4 (3 PHENYL 1,2,4 OXADIAZOL 5 YL)PIPERAZINE 1 CARBOXYLATE; TERT BUTYL 4 (4 PHENYLTHIAZOL 2 YL)PIPERAZINE 1 CARBOXYLATE; TERT BUTYL 4 [4 (2 FLUOROPHENYL)THIAZOL 2 YL]PIPERAZINE 1 CARBOXYLATE; TERT BUTYL 4 [4 (2,4 DIFLUOROPHENYL)THIAZOL 2 YL]PIPERAZINE 1 CARBOXYLATE; TERT BUTYL 4 [4 (3 FLUOROPHENYL)THIAZOL 2 YL]PIPERAZINE 1 CARBOXYLATE; TERT BUTYL 4 [4 (4 FLUOROPHENYL)THIAZOL 2 YL]PIPERAZINE 1 CARBOXYLATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; UREA DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINOCICEPTION; AREA UNDER THE CURVE; ARTICLE; BLOOD BRAIN BARRIER; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BRAIN LEVEL; DRUG PENETRATION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; EXPERIMENTAL RAT; IN VITRO STUDY; IN VIVO STUDY; MEMBRANE PERMEABILITY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; WRITHING TEST;

AMIDOHYDROLASES; ANALGESICS; ANIMALS; HUMANS; MICE; MOLECULAR DOCKING SIMULATION; PAIN; PIPERAZINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; UREA;

MUS;

EID: 84870899579     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2012.11.006     Document Type: Article

References (54)

1. B.F. Cravatt, D.K. Giang, S.P. Mayfield, D.L. Bogar, R.A. Lerner, and N.B. Gilula Nature 384 1996 83
2. D.K. Giang, and B.F. Cravatt Proc. Natl. Acad. Sci. U.S.A. 94 1997 2238
3. D.G. Deutsch, N. Ueda, and N. Yamamoto Prostaglandins Leukot. Essent. Fatty Acids 66 2002 201
4. M.P. Patricelli, and B.F. Cravatt Vitam. Horm. 62 2001 95
5. M. Egertova, B.F. Cravatt, and M.R. Elphick J. Neurosci. 119 2003 481
6. D.L. Boger, R.A. Fecik, J.E. Patterson, H. Miyauchi, M.P. Patricelli, and B.F. Cravatt Bioorg. Med. Chem. Lett. 10 2000 2613
7. C. Ezzili, K. Otrubova, and D.L. Boger Bioorg. Med. Chem. Lett. 20 2010 5959
8. W.A. Devane, L. Hanus, A. Breuer, R.G. Pertwee, L.A. Stevenson, G. Griffin, D. Gibson, A. Mandelbaum, A. Etinger, and R. Mechoulam J. Neurosci. 258 1992 1946
9. B.R. Martin, R. Mechoulam, and R.K. Razdan Life Sci. 65 1999 573
10. V. Di Marzo, T. Bisogno, L. De Petrocellis, D. Melck, and B.R. Martin Curr. Med. Chem. 6 1999 721
11. H.H.O. Schmid, P.C. Schmid, and V. Natarajan Prog. Lipid Res. 29 1990 1
12. D.L. Boger, S.J. Henriksen, and B.F. Cravatt Curr. Pharm. Des. 4 1998 303
13. B.F. Cravatt, R.A. Lerner, and D.L. Boger J. Am. Chem. Soc. 118 1996 580
14. B.F. Cravatt, O. Prospero-Garcia, G. Suizdak, N.B. Gilula, S.J. Henriksen, D.L. Boger, and R.A. Lerner J. Neurosci. 268 1995 1506
15. R.A. Lerner, G. Siuzdak, O. Prospero-Garcia, S.J. Henriksen, D.L. Boger, and B.F. Cravatt Proc. Natl. Acad. Sci. U.S.A. 91 1994 9505
16. F. Rodriguez de Fonseca, M. Navarro, R. Gomez, L. Escuredo, F. Nava, J. Fu, E. Murillo-Rodriguez, A. Giuffrida, J. Lo Verme, S. Gaetani, S. Kathuria, C. Gall, and D. Piomelli Nature 414 2001 219
17. S.K. Goparaju, N. Ueda, K. Taniguchi, and S. Yamamoto Biochem. Pharmacol. 57 1999 417
18. J.M. Walker, S.M. Huang, N.M. Strangman, K. Tsou, and M.C. Sanudo-Pena Proc. Natl. Acad. Sci. U.S.A. 96 1999 12198
19. D.M. Lambert, and C.J. Fowler J. Med. Chem. 48 2005 5059
20. P. Pacher, S. Batkai, and G. Kunos Pharmacol. Rev. 58 2006 389
21. V. Di Marzo Nat. Rev. Drug Disc. 7 2008 438
22. C. Thabuis, F. Destaillats, D. Tissot-Favre, and J.C. Martin Lip Technol. 19 2007 225
23. B.F. Cravatt, K. Demarest, M.P. Patricelli, M.H. Bracey, D.K. Giang, B.R. Martin, and A.H. Lichtman Proc. Natl. Acad. Sci. U.S.A. 98 2001 9371
24. B. Angela, E. Clement, H. Gregory, H.L. Aron, and F.C. Benjamin J. Neurosci. 23 2003 3916
25. A.H. Lichtman, C.C. Shelton, T. Advani, and B.F. Cravatt Pain 109 2004 319
26. L.A. Matsuda, S.J. Lolait, M.J. Brownstein, A.C. Young, and T.I. Bonner Nature 346 1990 561
27. J.D. Richardson, L. Aanonsen, and K.M. Hargreaves Eur. J. Pharmacol. 345 1998 145
28. V. Di Marzo, L. De Petrocellis, F. Fezza, A. Ligresti, and T. Bisogno Prostaglandins Leukot. Essent. Fatty Acids 66 2002 377
29. K.D. Patel, J.S. Davison, Q.J. Pittman, and K.A. Sharkey Curr. Med. Chem. 14 2010 1393
30. C. Benito, R.M. Tolón, M.R. Pazos, E. Núñez, A.L. Castillo, and J. Romero Br. J. Pharmacol. 2 2008 277
31. F.A. Moreira, M. Grieb, and B. Lutz Best Pract. Res. Clin. Endocrinol. Metab. 12 2009 1647
32. M. Karst, and S. Wippermann Expert Opin. Invest. Drugs 2 2009 125
33. S. Kathuria, S. Gaetani, D. Fegley, F. Valino, A. Duranti, A. Tontini, M. Mor, G. Tarzia, G.L. Rana, A. Calignano, A. Giustino, M. Tattoli, M. Palmery, V. Cuomo, and D. Piomelli Nat. Med. 9 2003 76
34. Abouab-Dellah, A.; Burnier, P.; Hoornaert, C.; Jeunesse, J.; Puech, F. Patent WO2004/099176, 2004; US2006/0089344, 2006.
35. K. Ahn, D.S. Johnson, L.R. Fitzgerald, M. Liimatta, A. Arendse, T. Stevenson, E.T. Lund, R.A. Nugent, T.K. Nomanbhoy, J.P. Alexander, and B.F. Cravatt Biochemistry 46 2007 13019
36. J.P. Alexander, and B.F. Cravatt J. Am. Chem. Soc. 128 2006 9699
37. D.L. Boger, H. Miyauchi, W. Du, C. Hardouin, R.A. Fecik, H. Cheng, I. Hwang, M.P. Hedrick, D. Leung, O. Acevedo, C.R.W. Guimaraes, W.L. Jorgensen, and B.F. Cravatt J. Med. Chem. 48 2005 1849
38. J.P. Alexander, and B.F. Cravatt Chem. Biol. 12 2005 1179
39. M. Mileni, J. Garfunkle, J.K. DeMartino, B.F. Cravatt, D.L. Boger, and R.C. Stevens J. Am. Chem. Soc. 30 2009 10497
40. M. Mileni, J. Garfunkle, C. Ezzili, F.S. Kimball, B.F. Cravatt, R.C. Stevens, and D.L. Boger J. Med. Chem. 1 2010 230
41. Compound 1 is reported as JNJ1661010: J.M. Keith, R. Apodaca, W. Xiao, M. Seierstad, K. Pattabiraman, J. Wu, M. Webb, M.J. Karbarz, S. Brown, S. Wilson, B. Scott, C.S. Tham, L. Luo, J. Palmer, M. Wennerholm, S. Chaplan, and J.G. Breitenbucher Bioorg. Med. Chem. Lett. 18 2008 4838
42. Our FAAH inhibitors are disclosed in our patent: Matsumoto, T.; Kori, M.; Miyazaki, J.; Kiyota, Y. Patent WO2006/054652, 2006; EP1813606, 2007; US2008/0312226, 2008.
43. Similar urea-type compounds have been reported: J.M. Meyers, A.S. Long, J.M. Pelc, L.J. Wang, J.S. Bowen, C.M. Walker, A.B. Schweitzer, M.H. Madsen, E.R. Tenbrink, J. McDonald, E.S. Smith, S. Foltin, F. Beidler, and A. Thorarensen Bioorg. Med. Chem. Lett. 21 2011 6538
44. J.M. Meyers, A.S. Long, J.M. Pelc, L.J. Wang, J.S. Bowen, A.B. Schweitzer, C.M. Wilcox, J. McDonald, E.S. Smith, S. Foltin, J. Rumsey, S.Y. Yang, C.M. Walker, S. Kamtekar, F. Beidler, and A. Thorarensen Bioorg. Med. Chem. Lett. 21 2011 6545
45. D.S. Johnson, K. Ahn, S. Kesten, S.E. Lazerwith, Y. Song, M. Morris, L. Fay, T. Gregory, C. Stiff, J.B. Dunbar, M. Liimatta, D. Beidler, S. Smith, T.K. Nomanbhoy, and B.F. Cravatt Bioorg. Med. Chem. Lett. 19 2009 2865
46. M.H. Bracey, M.A. Hanson, K.R. Masuda, R.C. Stevens, and B.F. Cravatt J. Neurosci. 298 2002 1793
47. Goerdeler Chem. Ber. 90 1957 182
48. D. Frederic, C. Guy, P. Nicole, B. Didier, and H. Jean-Pierre Bioorg. Med. Chem. Lett. 14 2004 1119 1122
49. H. Beyer, and G. Ruhlig Chem. Ber. 89 1956 107
50. B.W. Thomas, and B.R.J. David Tetrahedron Lett. 27 1967 2555
51. P.M. Patricelli, A.H. Lashuel, K.D. Giang, W.J. Kelly, and B.F. Cravatt Biochemistry 37 1998 15177
52. Z. Otwinowski, and W. Minor Methods Enzymol. 276 1997 307
53. G.N. Murshudov, A.A. Vagin, and E.J. Dodson Acta Crystallogr. 53 1997 240
54. D.E. McRee J. Struct. Biol. 125 1999 156