Biphenyl-3-yl alkylcarbamates as fatty acid amide hydrolase (FAAH) inhibitors: Steric effects of N-alkyl chain on rat plasma and liver stability

European Journal of Medicinal Chemistry

Volumn 46, Issue 9, 2011, Pages 4466-4473

  Vacondio, Federica ^a   Silva, Claudia ^a   Lodola, Alessio ^a   Carmi, Caterina ^a   Rivara, Silvia ^a   Duranti, Andrea ^b   Tontini, Andrea ^b   Sanchini, Silvano ^b   Clapper, Jason R ^c   Piomelli, Daniele ^c,d   Tarzia, Giorgio ^b   Mor, Marco ^a  

^a UNIVERSITY OF PARMA   (Italy)

^b UNIVERSITY OF URBINO   (Italy)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

Author keywords

Alkylcarbamates; FAAH inhibitors; Liquid chromatography; Rat plasma; SPR; Stability

Indexed keywords

ALKYL GROUP; CARBAMIC ACID DERIVATIVE; CYCLOHEXYLCARBAMIC ACID 3' CARBAMOYLBIPHENYL 3 YL ESTER; ESTERASE; FATTY ACID AMIDASE INHIBITOR; NITROGEN; SOLVENT; UNCLASSIFIED DRUG; URB 694; URB 937;

ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; DRUG BLOOD LEVEL; DRUG DEGRADATION; DRUG EFFECT; DRUG POTENCY; DRUG STRUCTURE; ENZYME STABILITY; FRACTIONATION; HYDROLYSIS; IN VITRO STUDY; LIPOPHILICITY; LIVER; MALE; NONHUMAN; PHYSICAL CHEMISTRY; RAT; STRUCTURE ACTIVITY RELATION;

AMIDOHYDROLASES; ANIMALS; AREA UNDER CURVE; BLOOD; CARBAMATES; ENZYME INHIBITORS; LIVER; MALE; RATS; RATS, WISTAR;

EID: 80052918371     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2011.07.021     Document Type: Article

References (59)

1. F. Desarnaud, H. Cadas, and D. Piomelli Anandamide amidohydrolase activity in rat brain microsomes. Identification and partial characterization J. Biol. Chem. 270 1995 6030 6035
2. N. Ueda, Y. Kurahashi, S. Yamamoto, and T. Tokunaga Partial purification and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide J. Biol. Chem. 270 1995 23823 23827
3. C.J. Hillard, D.M. Wilkison, W.S. Edgemond, and W.B. Campbell Characterization of the kinetics and distribution of N-arachidonylethanolamine (anandamide) hydrolysis by rat brain Biochim. Biophys. Acta 1257 1995 249 256
4. B.F. Cravatt, D.K. Giang, S.P. Mayfield, D.L. Boger, R.A. Lerner, and N.B. Gilula Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides Nature 384 1996 83 87
5. B.Q. Wei, T.S. Mikkelsen, M.K. McKinney, E.S. Lander, and B.F. Cravatt A second fatty acid amide hydrolase with variable distribution among placental mammals J. Biol. Chem. 281 2006 36569 36578
6. W.A. Devane, L. Hanuš, A. Breuer, R.G. Pertwee, L.A. Stevenson, G. Griffin, D. Gibson, A. Mandelbaum, A. Etinger, and R. Mechoulam Isolation and structure of a brain constituent that binds to the cannabinoid receptor Science 258 1992 1946 1949
7. F. Rodríguez de Fonseca, M. Navarro, R. Gómez, L. Escuredo, F. Nava, J. Fu, E. Murillo-Rodríguez, A. Giuffrida, J. LoVerme, S. Gaetani, S. Kathuria, C. Gall, and D. Piomelli An anorexic lipid mediator regulated by feeding Nature 414 2001 209 212
8. J. Fu, S. Gaetani, F. Oveisi, J. Lo Verme, A. Serrano, F. Rodríguez De Fonseca, A. Rosengarth, H. Luecke, B. Di Giacomo, G. Tarzia, and D. Piomelli Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α Nature 425 2003 90 93
9. T. Bisogno, S. Maurelli, D. Melck, L. De Petrocellis, and V. Di Marzo Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes J. Biol. Chem. 272 1997 3315 3323
10. C. Solorzano, C. Zhu, N. Battista, G. Astarita, A. Lodola, S. Rivara, M. Mor, R. Russo, M. Maccarrone, F. Antonietti, A. Duranti, A. Tontini, S. Cuzzocrea, G. Tarzia, and D. Piomelli Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation Proc. Natl. Acad. Sci. U.S.A. 106 2009 20966 20971
11. C. Solorzano, F. Antonietti, A. Duranti, A. Tontini, S. Rivara, A. Lodola, F. Vacondio, G. Tarzia, D. Piomelli, and M. Mor Synthesis and structure-activity relationships of N-(2-oxo-3-oxetanyl)amides as N-acylethanolamine-hydrolyzing acid amidase inhibitors J. Med. Chem. 53 2010 5770 5781
12. V. Di Marzo Targeting the endocannabinoid system: to enhance or reduce? Nat. Rev. Drug Discov. 7 2008 438 455
13. H. Deng Recent advances in the discovery and evaluation of fatty acid amide hydrolase inhibitors Exp. Opin. Drug Discov. 5 2010 961 993
14. S.Y. Sit, C.M. Conway, K. Xie, R. Bertekap, C. Bourin, and K.D. Burris Oxime carbamate-discovery of a series of novel FAAH inhibitors Bioorg. Med. Chem. Lett. 20 2010 1272 1277
15. S. Gattinoni, C. De Simone, S. Dallavalle, F. Fezza, R. Nannei, N. Battista, P. Minetti, G. Quattrociocchi, A. Caprioli, F. Borsini, W. Cabri, S. Penco, L. Merlini, and M. Maccarrone A new group of oxime carbamates as reversible inhibitors of fatty acid amide hydrolase Bioorg. Med. Chem. Lett. 20 2010 4406 4411
16. D.J. Gustin, Z. Ma, X. Min, Y. Li, C. Hedberg, C. Guimaraes, A.C. Porter, M. Lindstrom, D. Lester-Zeiner, G. Xu, T.J. Carlson, S. Xiao, C. Meleza, R. Connors, Z. Wang, and F. Kayser Identification of potent, noncovalent fatty acid amide hydrolase (FAAH) inhibitors Bioorg. Med. Chem. Lett. 21 2011 2492 2496
17. D.S. Johnson, C. Stiff, S.E. Lazerwith, S.R. Kesten, L.K. Fay, M. Morris, D. Beidler, M.B. Liimatta, S.E. Smith, D.T. Dudley, N. Sadagopan, S.N. Bhattachar, S.J. Kesten, T.K. Nomanbhoy, B.F. Cravatt, and K. Ahn Discovery of PF-04457845: a highly potent, orally bioavailable, and selective urea FAAH inhibitor ACS Med. Chem. Lett. 2 2011 91 96
18. S. Kathuria, S. Gaetani, D. Fegley, F. Valiño, A. Duranti, A. Tontini, M. Mor, G. Tarzia, G. La Rana, A. Calignano, A. Giustino, M. Tattoli, M. Palmery, V. Cuomo, and D. Piomelli Modulation of anxiety through blockade of anandamide hydrolysis Nat. Med. 9 2003 76 81
19. G. Tarzia, A. Duranti, A. Tontini, G. Piersanti, M. Mor, S. Rivara, P.V. Plazzi, C. Park, S. Kathuria, and D. Piomelli Design, synthesis, and structure-activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitors J. Med. Chem. 46 2003 2352 2360
20. M. Mor, S. Rivara, A. Lodola, P.V. Plazzi, G. Tarzia, A. Duranti, A. Tontini, G. Piersanti, S. Kathuria, and D. Piomelli Cyclohexylcarbamic acid 3'- or 4'-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies J. Med. Chem. 47 2004 4998 5008
21. D. Piomelli, G. Tarzia, A. Duranti, A. Tontini, M. Mor, T.R. Compton, O. Dasse, E.P. Monaghan, J.A. Parrott, and D. Putman Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597) CNS Drug Rev. 12 2006 21 38
22. G. Tarzia, A. Duranti, G. Gatti, G. Piersanti, A. Tontini, S. Rivara, A. Lodola, P.V. Plazzi, M. Mor, S. Kathuria, and D. Piomelli Synthesis and structure-activity relationships of FAAH inhibitors: cyclohexylcarbamic acid biphenyl esters with chemical modulation at the proximal phenyl ring ChemMedChem 1 2006 130 139
23. F. Vacondio, C. Silva, A. Lodola, A. Fioni, S. Rivara, A. Duranti, A. Tontini, S. Sanchini, J.R. Clapper, D. Piomelli, M. Mor, and G. Tarzia Structure-property relationships of a class of carbamate-based fatty acid amide hydrolase (FAAH) inhibitors: chemical and biological stability ChemMedChem 4 2009 1495 1504
24. J.R. Clapper, F. Vacondio, A.R. King, A. Duranti, A. Tontini, C. Silva, S. Sanchini, G. Tarzia, M. Mor, and D. Piomelli A second generation of carbamate-based fatty acid amide hydrolase inhibitors with improved activity in vivo ChemMedChem 4 2009 1505 1513
25. J.R. Clapper, G. Moreno-Sanz, R. Russo, F. Vacondio, A. Duranti, A. Tontini, S. Sanchini, N.R. Sciolino, J.M. Spradley, A.G. Hohmann, A. Calignano, M. Mor, G. Tarzia, and D. Piomelli Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism Nat. Neurosci. 13 2010 1265 1270
26. G. Gobbi, F.R. Bambico, R. Mangieri, M. Bortolato, P. Campolongo, M. Solinas, T. Cassano, M.G. Morgese, G. Debonnel, A. Duranti, A. Tontini, G. Tarzia, M. Mor, V. Trezza, S.R. Goldberg, V. Cuomo, and D. Piomelli Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis Proc. Natl. Acad. Sci. U.S.A. 102 2005 18620 18625
27. M. Bortolato, R.A. Mangieri, J. Fu, J.H. Kim, O. Arguello, A. Duranti, A. Tontini, M. Mor, G. Tarzia, and D. Piomelli Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress Biol. Psychiatry 62 2007 1103 1110
28. R. Russo, J. LoVerme, G. La Rana, T.R. Compton, J. Parrott, A. Duranti, A. Tontini, M. Mor, G. Tarzia, A. Calignano, and D. Piomelli The fatty acid amide hydrolase inhibitor URB597 (cyclohexylcarbamic acid 3'-carbamoylbiphenyl- 3-yl ester) reduces neuropathic pain after oral administration in mice J. Pharmacol. Exp. Ther. 322 2007 236 242
29. E. Basso, A. Duranti, M. Mor, D. Piomelli, A. Tontini, G. Tarzia, and P. Traldi Tandem mass spectrometric data-FAAH inhibitory activity relationships of some carbamic acid O-aryl esters J. Mass Spectrom. 39 2004 1450 1455
30. J.P. Alexander, and B.F. Cravatt Mechanism of carbamate inactivation of FAAH: implications for the design of covalent inhibitors and in vivo functional probes for enzymes Chem. Biol. 12 2005 1179 1187
31. A. Lodola, M. Mor, S. Rivara, C. Christov, G. Tarzia, D. Piomelli, and A.J. Mulholland Identification of productive inhibitor binding orientation in fatty acid amide hydrolase (FAAH) by QM/MM mechanistic modelling Chem. Commun. 2008 214 216
32. A. Lodola, L. Capoferri, S. Rivara, E. Chudyk, J. Sirirak, E. Dyguda-Kazimierowicz, W.A. Sokalski, M. Mileni, G. Tarzia, D. Piomelli, M. Mor, and A.J. Mulholland Understanding the role of carbamate reactivity in fatty acid amide hydrolase inhibition by QM/MM mechanistic modelling Chem. Commun. 2011 2517 2519
33. D. Zhang, A. Saraf, T. Kolasa, P. Bhatia, G.Z. Zheng, M. Patel, G.S. Lannoye, P. Richardson, A. Stewart, J.C. Rogers, J.D. Brioni, and C.S. Surowy Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets Neuropharmacology 52 2007 1095 1105
34. M. Mileni, J. Garfunkle, J.K. Demartino, B.F. Cravatt, D.L. Boger, and R.C. Stevens Binding and inactivation mechanism of a humanized fatty acid amide hydrolase by α-ketoheterocycle inhibitors revealed from cocrystal structures J. Am. Chem. Soc. 131 2009 10497 10506
35. M. Mileni, S. Kamtekar, D.C. Wood, T.E. Benson, B.F. Cravatt, and R.C. Stevens Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation J. Mol. Biol. 400 2010 743 754
36. M. Mileni, J. Garfunkle, C. Ezzili, F.S. Kimball, B.F. Cravatt, R.C. Stevens, and D.L. Boger X-ray crystallographic analysis of α- ketoheterocycle inhibitors bound to a humanized variant of fatty acid amide hydrolase J. Med. Chem. 53 2010 230 240
37. X. Min, S.T. Thibault, A.C. Porter, D.J. Gustin, T.J. Carlson, H. Xu, M. Lindstrom, G. Xu, C. Uyeda, Z. Ma, Y. Li, F. Kayser, N.P.C. Walker, and Z. Wang Discovery and molecular basis of potent noncovalent inhibitors of fatty acid amide hydrolase (FAAH) Proc. Natl. Acad. Sci. U. S. A. 108 2011 7379 7384
38. M. Mor, A. Lodola, S. Rivara, F. Vacondio, A. Duranti, A. Tontini, S. Sanchini, G. Piersanti, J.R. Clapper, A.R. King, G. Tarzia, and D. Piomelli Synthesis and quantitative structure-activity relationship of fatty acid amide hydrolase inhibitors: modulation at the N-portion of biphenyl-3-yl alkylcarbamates J. Med. Chem. 51 2008 3487 3498
39. A. Williams, and K.T. Douglas Elimination-addition mechanisms of acyl transfer reactions Chem. Rev. 75 1975 627 649
40. P. Adams, and F.A. Baron Esters of carbamic acid Chem. Rev. 65 1965 567 602
41. I. Christenson Alkaline hydrolysis of some carbamic acid esters Acta Chem. Scand. 18 1964 904 922
42. A.F. Hegarty, and L.N. Frost Elimination-addition mechanism for the hydrolysis of carbamates. Trapping of an isocyanate intermediate by an o-amino-group J. Chem. Soc. Perkin Trans. 2 1973 1719 1728
43. B. Testa, and S.D. Krämer The Biochemistry of Drug Metabolism: Principles, Redox Reactions, Hydrolyses 2008 Helvetica Chimica Acta Zurich pp. 201-248
44. F. Vacondio, C. Silva, M. Mor, and B. Testa Qualitative structure-metabolism relationships in the hydrolysis of carbamates Drug Metab. Rev. 42 2010 551 589
45. 3 receptor Chem. Biodivers. 5 2008 140 152
46. R.E. Fessey, R.P. Austin, P. Barton, A.M. Davis, and M.C. Wenlock The role of plasma protein binding in drug discovery B. Testa, S.D. Krämer, H. Wunderli-Allenspach, G. Folkers, Pharmacokinetic profiling in drug research 2006 VHCA Zurich 137 139
47. A. Verloop, and J. Tipker Physical basis of sterimol and related steric constants D. Hadzi, B. Jerman-Blazic, Pharmacochemistry Library, QSAR in Drug Design and Toxicology vol. 10 1987 Elsevier Amsterdam 97 102
48. P. Buchwald Structure-metabolism relationships: steric effects and the enzymatic hydrolysis of carboxylic esters Mini Rev. Med. Chem. 1 2001 101 111
49. P. Buchwald, and N. Bodor Quantitative structure-metabolism relationships: steric and nonsteric effects in the enzymatic hydrolysis of noncongener carboxylic esters J. Med. Chem. 42 1999 5160 5168
50. M. Hirota, K. Sakakibara, T. Yuzuri, and S. Kuroda Evaluation of the steric substituent effect by Ωs: reinvestigation of the reaction dependency of the steric substituent constant J. Phys. Org. Chem. 14 2001 788 793
51. B. Testa, H. van de Waterbeemd, G. Folkers, and R. Guy Pharmacokinetic optimization in drug research 2001 Helvetica Chimica Acta Zurich pp. 231-234
52. C.M. Masimirembwa, U. Bredberg, and T.B. Andersson Metabolic stability for drug discovery and development: pharmacokinetic and biochemical challenges Clin. Pharmacokinet. 42 2003 515 528
53. M.M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal. Biochem. 72 1976 248 254
54. MacroModel, version 9.7 2009 Schrödinger, LLC New York, NY
55. G.A. Kaminski, R.A. Friesner, J. Tirado-Rives, and W.L. Jorgensen Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides J. Phys. Chem. B. 105 2001 6474 6487
56. A. Ghosh, C. Sendrovic Rapp, and R.A. Friesner Generalized born model based on a surface integral formulation J. Phys. Chem. B. 102 1998 10983 10990
57. Maestro, version 9.0 2009 Schrödinger, LLC New York, NY
58. Qikprop, version 3.2 2009 Schrödinger, LLC New York, NY
59. Molecular Operating Environment (MOE 2008.10), C. C. G., Inc., 1255 University St. Montreal, Quebec, Canada H3B 3X3.