Targeting soluble epoxide hydrolase for inflammation and pain - an overview of pharmacology and the inhibitors

Inflammation and Allergy - Drug Targets

Volumn 11, Issue 2, 2012, Pages 143-158

  Pillarisetti, Sivaram ^a   Khanna, Ish ^a  

^a Kareus Therapeutics SA   (Swaziland)

Author keywords

Arthritis; Atherosclerosis; Cardiovascular; Colitis; Diabetes; Inflammation; Pain

Indexed keywords

1 ADAMANTAN 3 [5 [2 (2 ETHYLETHOXY)ETHOXY]PENTYL]UREA; 1 [3 (MORPHOLINE) 4 CARBONYLPHENYL] 3 (4 TRIFLUOROMETHYLPHENYL)UREA; 12 (3 ADAMANTAN 1 YLUREIDO) DODECANOIC ACID BUTYL ESTER; 4 [4 (3 ADAMANTAN 1 YLUREIDO)CYCLOHEXYLOXY]BENZOIC ACID; ANALGESIC AGENT; ANTIHYPERTENSIVE AGENT; ANTIINFLAMMATORY AGENT; AR 9281; ARACHIDONIC ACID; CARDIOVASCULAR AGENT; CYCLIC AMP; CYTOCHROME P450; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; EPOXIDE HYDROLASE; EPOXIDE HYDROLASE INHIBITOR; EPOXYICOSATRIENOIC ACID; G PROTEIN COUPLED RECEPTOR; HYDROLASE INHIBITOR; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1ALPHA; METHOTREXATE; MORPHINE; NONSTEROID ANTIINFLAMMATORY AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROSTAGLANDIN E2; STEROID; TRANSCRIPTION FACTOR RELA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1;

ANALGESIC ACTIVITY; ANTIHYPERTENSIVE ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ARACHIDONIC ACID METABOLISM; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR EFFECT; CARDIOVASCULAR SYSTEM; CATALYSIS; CELL MIGRATION; CHRONIC INFLAMMATION; CIGARETTE SMOKING; COLITIS; CRYSTAL STRUCTURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DESIGN; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME STRUCTURE; EPOXIDATION; HIGH THROUGHPUT SCREENING; HUMAN; HYDROLYSIS; HYPERALGESIA; HYPERTENSION; LIPID DEGRADATION; MEDIATOR RELEASE; METABOLIC DISORDER; NEPHRITIS; NEUROPATHIC PAIN; NONHUMAN; PAIN; PHARMACOLOGICAL BLOCKING; PNEUMONIA; RESTENOSIS; REVIEW; RHEUMATOID ARTHRITIS; SMOOTH MUSCLE FIBER; THROMBOCYTE AGGREGATION; VASCULAR SMOOTH MUSCLE;

EID: 84857740699     PISSN: 18715281     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152812800392823     Document Type: Review

References (103)

1. Harizi, H.; Corcuff, J.B.; Gualde, N. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol. Med., 2008, 14, 461-469.
2. Spector, A.A. Arachidonic acid cytochrome P450 epoxygenase pathway. J. Lipid Res., 2009, (50Suppl), S52-S56.
3. Pfister, S.L.; Gauthier, K.M.; Campbell, W.B. Vascular pharmacology of epoxyeicosatrienoic acids. Adv. Pharmacol., 2010, 60, 27-59.
4. Imig, J.D.; Hammock, B.D. Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat. Rev. Drug Discov., 2009, 8, 794-805.
5. Revermann, M. Pharmacological inhibition of the soluble epoxide hydrolase-from mouse to man. Curr. Opin. Pharmacol., 2010, 10, 173-178.
6. Node, K.; Huo, Y.; Ruan, X.; Yang, B.; Spiecker, M.; Ley, K.; Zeldin, D.C.; Liao, J.K. Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science, 1999, 285, 1276-1279.
7. Fang, X.; Moore, S.A.; Stoll, L.L.; Rich, G.; Kaduce, T.L.; Weintraub, N.L.; Spector, A.A. 14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells. Am. J. Physiol., 1998, 275, H2113-2121.
8. Pratt, P.F.; Rosolowsky, M.; Campbell, W.B. Effects of epoxyeicosatrienoic acids on polymorphonuclear leukocyte function. Life Sci., 2002, 70, 2521-2533.
9. Morin, C.; Sirois, M.; Echavé, V.; Albadine, R.; Rousseau, E. 17,18-epoxyeicosatetraenoic acid targets PPARγ and p38 mitogenactivated protein kinase to mediate its anti-inflammatory effects in the lung: role of soluble epoxide hydrolase. Am. J. Respir. Cell Mol. Biol., 2010, 43, 564-575.
10. Seki, K.; Hirai, A.; Noda, M.; Tamura, Y.; Kato, I.; Yoshida, S. Epoxyeicosatrienoic acid stimulates ADP-ribosylation of a 52 kDa protein in rat liver cytosol. Biochem. J., 1992, 281, 185-190.
11. Node, K.; Ruan, X.L.; Dai, J.; Yang, S.X.; Graham, L.; Zeldin, D.C.; Liao, J.K. Activation of Galpha s mediates induction of tissue-type plasminogen activator gene transcription by epoxyeicosatrienoic acids. J. Biol. Chem., 2001, 276, 15983-15989.
12. Wong, P.Y.; Lai, P.S.; Shen, S.Y.; Belosludtsev, Y.Y.; Falck, J.R. Post-receptor signal transduction and regulation of 14[R], 15[S]-epoxyeicosatrienoic acid [14,15-EET] binding in U-937 cells. J. Lipid Mediat. Cell Signal., 1997, 16, 155-169.
13. Ollivier, V.; Parry, G.C.; Cobb, R.R.; de Prost, D.; Mackman, N. Elevated cyclic AMP inhibits NF-kappaB-mediated transcription in human monocytic cells and endothelial cells. J. Biol. Chem., 1996, 271, 20828-20835.
14. Boswell-Smith, V.; Spina, D.; Page, C.P. Phosphodiesterase inhibitors. Br. J. Pharmacol., 2006, 147 (Suppl 1), S252-257.
15. Liu, Y.; Zhang, Y.; Schmelzer, K.; Lee, T.S.; Fang, X.; Zhu, Y.; Spector, A.A.; Gill, S.; Morisseau, C.; Hammock, B.D.; Shyy, J.Y. The antiinflammatory effect of laminar flow: the role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase. Proc. Natl. Acad. Sci. U S A., 2005, 102, 16747-16752.
16. Farmer, S.R. Regulation of PPARgamma activity during adipogenesis. Int J Obes [Lond]., 2005, 29 (Suppl 1), S13-6.
17. Chen, Y.; Falck, J.R.; Manthati, V.L.; Jat, J.L.; Campbell, W.B. 20-Iodo-14,15-epoxyeicosa-8[Z]-enoyl-3-azidophenylsulfonamide: photoaffinity labeling of a 14,15-epoxyeicosatrienoic acid receptor. Biochemistry, 2011, 50, 3840-3848.
18. Yang, C.; Kwan, Y.W.; Au, A.L.; Poon, C.C.; Zhang, Q.; Chan, S.W.; Lee, S.M.; Leung, G.P. 14,15-Epoxyeicosatrienoic acid induces vasorelaxation through the prostaglandin EP[2] receptors in rat mesenteric artery. Prostaglandins Other Lipid Mediat., 2010, 93, 44-51.
19. Gross, G.J.; Baker, J.E.; Hsu, A.; Wu, H.E.; Falck, J.R.; Nithipatikom, K. Evidence for a role of opioids in epoxyeicosatrienoic acid-induced cardioprotection in rat hearts. Am. J. Physiol. Heart Circ. Physiol., 2010, 298, H2201-2207.
20. Terashvili, M.; Tseng, L.F.; Wu, H.E.; Narayanan, J.; Hart, L.M.; Falck, J.R.; Pratt, P.F.; Harder, D.R. Antinociception produced by 14,15-epoxyeicosatrienoic acid is mediated by the activation of beta-endorphin and met-enkephalin in the rat ventrolateral periaqueductal gray. J. Pharmacol. Exp. Ther., 2008, 326, 614-622.
21. Behm, D.J.; Ogbonna, A.; Wu, C.; Burns-Kurtis, C.L.; Douglas, S.A. Epoxyeicosatrienoic acids function as selective, endogenous antagonists of native thromboxane receptors: identification of a novel mechanism of vasodilation. J. Pharmacol. Exp. Ther., 2009, 328, 231-239.
22. Schmelzer, K.R.; Kubala, L.; Newman, J.W.; Kim, I.H.; Eiserich, J.P.; Hammock, B.D. Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc. Natl. Acad. Sci. U S A., 2005, 102, 9772-9777.
23. Liu, J.Y.; Yang, J.; Inceoglu, B.; Qiu, H.; Ulu, A.; Hwang, S.H.; Chiamvimonvat N, Hammock BD. Inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model. Biochem. Pharmacol., 2010, 79, 880-887.
24. Ross, R.; Atherosclerosis--an inflammatory disease. N. Engl. J. Med., 1999, 340, 115-126.
25. Wang, Y.X.; Ulu, A.; Zhang, L.N.; Hammock, B. Soluble epoxide hydrolase in atherosclerosis. Curr. Atheroscler. Rep., 2010, 12, 174-183.
26. Fornage, M.; Boerwinkle, E.; Doris, P.A.; Jacobs, D.; Liu, K.; Wong, N.D. Polymorphism of the soluble epoxide hydrolase is associated with coronary artery calcification in African-American subjects: The Coronary Artery Risk Development in Young Adults [CARDIA] study. Circulation, 2004, 109, 335-339.
27. Lee, C.R.; North, K.E.; Bray, M.S.; Fornage, M.; Seubert, J.M.; Newman, J.W.; Hammock, B.D.; Couper, D.J.; Heiss, G.; Zeldin, D.C. Genetic variation in soluble epoxide hydrolase [EPHX2] and risk of coronary heart disease: The Atherosclerosis Risk in Communities [ARIC] study Hum. Mol. Genet., 2006, 15, 1640-1649.
28. Ulu, A.; Davis, B.B.; Tsai, H.J.; Kim, I.H.; Morisseau, C.; Inceoglu, B.; Fiehn, O.; Hammock, B.D.; Weiss, R.H. Soluble epoxide hydrolase inhibitors reduce the development of atherosclerosis in apolipoprotein e-knockout mouse model. J. Cardiovasc. Pharmacol., 2008, 52, 314-323.
29. Revermann, M.; Schloss, M.; Barbosa-Sicard, E.; Mieth, A.; Liebner, S.; Morisseau, C.; Geisslinger, G.; Schermuly, R.T.; Fleming, I.; Hammock, B.D.; Brandes, R.P. Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice. Arterioscler. Thromb. Vasc. Biol., 2010, 30, 909-914.
30. Manhiani, M.; Quigley, J.E.; Knight, S.F.; Tasoobshirazi, S.; Moore, T.; Brands, M.W.; Hammock, B.D.; Imig, J.D. Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension. Am. J. Physiol. Renal Physiol., 2009, 297, F740-748.
31. Elmarakby, A.A.; Faulkner, J.; Al-Shabrawey, M.; Wang, M.H.; Maddipati, K.R.; Imig, J.D. Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2011, 301, R1307-1317.
32. Smith, K.R.; Pinkerton, K.E.; Watanabe, T.; Pedersen, T.L.; Ma, S.J.; Hammock, B.D. Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor. Proc. Natl. Acad. Sci. U S A., 2005, 102, 2186-91.
33. Deng, Y.; Edin, M.L.; Theken, K.N.; Schuck, R.N.; Flake, G.P.; Kannon, M.A.; DeGraff, L.M.; Lih, F.B.; Foley, J.; Bradbury, J.A.; Graves, J.P.; Tomer, K.B.; Falck, J.R.; Zeldin, D.C.; Lee, C.R. Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice. FASEB J., 2011, 25, 703-713.
34. Morin, C.; Sirois, M.; Echavé, V.; Albadine, R.; Rousseau, E. 17,18-epoxyeicosatetraenoic acid targets PPARγ and p38 mitogenactivated protein kinase to mediate its anti-inflammatory effects in the lung: role of soluble epoxide hydrolase. Am. J. Respir. Cell Mol. Biol., 2010, 43, 564-575.
35. Breedveld, F.C.; Combe, B. Understanding emerging treatment paradigms in rheumatoid arthritis. Arthritis Res. Ther., 2011, 13 (Suppl 1), S3.
36. Hsu, H.K. Soluble epoxide hydrolase inhibitors in the treatment of arthritis. US Patent 221,104 A1; 2008.
37. Mattar, M.C.; Lough, D.; Pishvaian, M.J.; Charabaty, A. Current management of inflammatory bowel disease and colorectal cancer. Gastrointest. Cancer Res., 2011, 4, 53-61.
38. Norwood, S.; Liao, J.; Hammock, B.D.; Yang, G.Y. Epoxyeicosatrienoic acids and soluble epoxide hydrolase: potential therapeutic targets for inflammation and its induced carcinogenesis. Am. J. Transl. Res., 2010, 2, 447-457.
39. Terashvili, M.; Tseng, L.F.; Wu, H.E.; Narayanan, J.; Hart, L.M.; Falck, J.R.; Pratt, P.F.; Harder, D.R. Antinociception produced by 14,15-epoxyeicosatrienoic acid is mediated by the activation of beta-endorphin and met-enkephalin in the rat ventrolateral periaqueductal gray. J. Pharmacol. Exp. Ther., 2008, 326, 614-622.
40. Inceoglu, B.; Jinks, S.L.; Ulu, A.; Hegedus, C.M.; Georgi, K.; Schmelzer, K.R.; Wagner, K.; Jones, P.D.; Morisseau, C.; Hammock, B.D. Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways. Proc. Natl. Acad. Sci. U S A., 2008, 105, 18901-18906.
41. Morisseau, C.; Hammock, B. Epoxide Hydrolases: Mechanism, inhibitor design and biological roles, Annu. Res. Pharmacol. Toxicol., 2005, 45, 311-333; and references cited therein.
42. Argiriadi, M.A.; Morisseau, C.; Hammock, B.D.; Christianson, D.W. Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of epoxide hydrolase. Proc. Nat, Acad. Sci. USA., 1999, 96, 10637-10642.
43. Falck, J.R.; Kodela, R.; Manne, R.; Atcha, K.R.; Puli, N.; Dubasi, N.; Manthati, V.L.; Capdevila, J.H.; Yi, X.Y.; Goldman, D.H.; Morisseau, C.; Hammock, B.D.; Campbell, W.B. 14,15-Epoxyeicosa-5,8,11-trienoic Acid [14,15-EET] Surrogates Containing Epoxide Bioisosteres: Influence upon Vascular Relaxation and Soluble Epoxide Hydrolase Inhibition. J. Med. Chem., 2009, 52, 5069-5075.
44. Hammock, B.D.; Grant, D. In Comprehensive Toxicology, Sipes, I.; McQueen, C.; Gandolfi, A.; Eds.; Oxford, Pergamon; 1997, pp 283-305
45. Spector, A.A.; Fang, X.; Snyder, G.D.; Weintraub, N.L.; Epoxyeicosatrienoic acids [EETs] metabolism and biochemical function. Prog. lipid Res., 43, 55-90, 2004.
46. Gaetke, L.M.; McClain, C.I.; Talwalker, R.T.; Shedlofsky, S.I. Effects of endotoxin on zinc metabolism in human volunteers. Am J. Physio. Endocrine Metab., 1997, 272, E952-956.
47. Morisseau, C.; Hammock, B.D. Epoxide hydrolases: mechanism, inhibitor designs, biological roles. Annu. Rev. Pharmacol. Toxicol., 2005, 45, 311-333.
48. Morisseau, C.; Goodrow, M.H.; Dowdy, D.; Zheng, J.; Greene, J.F.; Sanborn, J.R.; Hammock, B.D. Potent urea and carbamate inhibitors of soluble epoxide hydrolases. Proc. Natl. Acad. Sci. USA, 1999, 96, 8849-8854.
49. Fretland, A.J.; Omiecinski, C.L. Epoxide hydrolases: Biochemistry and molecular biology, Chem. Biol. Interact., 2000, 129, 41-59.
50. Shen, H.C. Soluble epoxide hydrolase inhibitors, a patent review. Expert Opin. Ther. Patents, 2010, 20, 941-956.
51. Revermann, M. Pharmacological inhibition of the soluble epoxide hydrolase - from mouse to man. Curr. Opin. Pharmacol., 2010, 10, 173-178.
52. Imig, J.D.; Hammock, B.D. Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat. Rev. Drug. Disc., 2009, 8, 794-805.
53. Marino, J. Soluble epoxide hydrolase, a target with multiple opportunities for cardiovascular drug discovery. Curr. Topics Med. Chem., 2009, 9, 452-463; and references therein.
54. Shen, H. C.; Hammock, B. C. Discovery of inhibitors of soluble epoxide hydrolase: A target with multiple potential therapeutic indications. J. Med. Chem., 2011, [in press].
55. Jones, P.D.; Tsai, H.J.; Do, Z.N.; Morisseau, C.; Hammock, B.D. Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase. Bioorg. Med. Chem. Lett., 2006, 16, 5212-5216.
56. Yu, Z.; Xu, F.; Huse, L.M.; Morisseau, C.; Draper, A.J.; Newman, J.W.; Parker, C.; Graham, L.; Engler, M.M.; Hammock, B.D.; Zeldin, D.C.; Kroetz, D.L. Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids. Circ. Res., 2000, 87, 992-998.
57. Imig, J.D.; Zhao, X.; Capdevila, J.H.; Morisseau, C.; Hammock, B.D. Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension, Hypertension, 2002, 39, 690-694.
58. Kim, I.H.; Hammock, B.D.; Design, synthesis and biological activity of 1,3 disubstituted ureas as potent inhibitors of the soluble epoxide hydrolase of increased water solubility. J. Med. Chem., 2004, 47, 2110-2122.
59. Imig, J.D.; Zhao, X.; Zaharis, C.Z.; Olearczyk, J.J.; Pollock, D.M.; Newman, J.W., Kim, I.H.; Watanabe, T.; Hammock, B.D. An orally active epoxide hydrolase inhibitor lowers blood pressure and provides renal protection in salt sensitive hypertension. Hypertension, 2005, 46, 975-981.
60. Inceoglu, B.; Jinks, S.L.; Schmelzer, K.R.; Waite, T.; Kim, I.H.; Hammock, B.D. Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain. Life Sci., 2006, 79, 2311-2319.
61. Dorrance, A.M.; Rupp, N.; Pollock, D.M.; Newman, J.W.; Hammock, B.D.; Imig, J.D. An epoxide hydrolase inhibitor AUDA reduces ischemic cerebral infarct size in stroke-prone spontaneously hypertensive rats. J. Cardio. Pharm. 2005, 46, 842-848.
62. Kim, L.H.; Tsai, H.J.; Nishi, K.; Kasagami, T.; Hammock, B.D. 1,3-disubstituted urea functionalized with ether group are potent inhibitors of soluble epoxide hydrolase with improved pharmacokinetic properties. J. Med. Chem., 2007, 50, 5217-5226.
63. Hwang, S.H.; Tsai, H.J.; Liu, J.Y.; Morisseau, C.; Hammock, B.D. Orally bioavailable potent soluble epoxide hydrolase inhibitors. J. Med. Chem., 2007, 50, 3825-3840.
64. Kasagami, T.; Kim, I.H.; Tsai, H.J.; Nishi, K.; Hammock, B.D.; Morisseau, C. Salicylate-urea based soluble epoxide hydrolase inhibitors with high metabolic and chemical stabilities. Bioorg. Med. Chem. Lett. 2009, 19, 1784-1789.
65. Rose, T.E.; Morisseau, C.; Liu, J.Y.; Inceoglu, B.; Jones, P.D.; Sanborn, J.R.; Hammock, B.D. [1-Aryl-3-[1-acylpiperidin-4-yl]urea Inhibitors of human and murine soluble epoxide hydrolase: structure-activity relationships, pharmacokinetics, and reduction of inflammatory pain. J. Med. Chem., 2010, 53, 7067-7075.
66. The reagents of the University of California. Alleviating neuropathic pain with EETs and sEH inhibitors. WO 2,209,062,073, 2006.
67. Webb, H.; Heather, K. Soluble epoxide hydrolase inhibitors, PCT Int. Appls., 058033A2, 2008; 094869A1, 2008; 051873A2, 2008; 051875A1, 2008.
68. Anandan, S.K.; Webb, H.K.; Do, Z.D.; Gless, R.D. Unsymmetrical non-adamantyl N,N-diaryl urea and amide inhibitors of soluble epoxide hydrolase. Bioorg. Med. Chem. Lett., 2009, 19, 4259-4263.
69. Anandan, S.K.; Gless, R.D. Exploration of secondary and tertiary pharmacophores in unsymmetrical N,N-diarylurea inhibitors of soluble epoxide hydrolase. Bioorg. Med. Chem. Lett., 2010, 20, 2740-2744.
70. Gless, D. Soluble epoxide hydrolase inhibitors. PCT Int. Appl., 035951, 2009; US Patent Appl., 0082395, 2009.
71. Anandan, S.K.; Webb, H.K.; Chen, D.; Wang, Y.X.; Aavula, B.R.; Cases, S.; Cheng, Y.; Do, Z.N.; Mehra, U.; Tran, V.; Vincelette, J.; Waszczuk, J.; White, K.; Wong, K.R.; Zhang, L.N.; Jones, P.D.; Hammock, B.D.; Patel, D.V.; Whitcomb, R.; MacIntyre, D.E.; Sabry, J.; Gless, R. AR 9281 as a potent, selective and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia. Biorg. Med. Chem. Letts., 2011, 21, 983-988.
72. Whitcomb, R.; Chen, D.; Wang Y-X.; Anandan, S. K.; Gless, R. AR9281, a soluble epoxide hydrolase inhibitor - efficacy in a DIO mouse model plus pharmacokinetics and pharmacodynamics in mice and men. 69th Annual Scientific Sessions of the American Diabetes Association. [plus poster] Abstr. 612-P, 5 Jun 2009. Available from: URL: http://ww2.aievolution.com.USA. Arete Therapeutics Inc. Arete Therapeutics Initiates Phase IIa Clinical Trial for AR9281, a Novel sEH Inhibitor to treat type 2 diabetes.www.aretetherapeutics.com, 10 Feb 2009; media release.
73. Imig, J.D.; Carpenter, M.A.; Shaw, S. The soluble epoxide hydrolase inhibitor AR 9281 decreases blood pressure, ameliorates renal injury and improves vascular function in hypertension, pharmaceuticals, 2009, 2, 217-227; Clinical trials.gov. ID NCT00847899.
74. The trial was terminated in November, 2009; Available at: http://clinicaltrials.gov/
75. Ota, T.; Takahashi, H.; Kakinuma, H.; Busujima, T. Preparation of benzimidazole-5-carboxamide derivatives as soluble epoxide hydrolase inhibitors. PCT Int. Appl., 43652, 2007.
76. Eldrup, A.B.; Soleymanzadeh, F.; Farrow, N.A.; Kukulka, A.; Lombaert, S. D. Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase. Bioorg. Med. Chem. Lett., 2010, 20, 571-575.
77. Kowalski, J.A.; Swinamer, A.D.; Muegge, I.; Eldrup, A.B.; Kukulka, A.; Cywinn, C.L.; Lombaert, S. D. Rapid synthesis of an array of trisubstituted urea based soluble epoxide hydrolase inhibitors facilitated by a novel solid phase method. Bioorg. Med. Chem. Lett., 2010, 20, 3703-3710.
78. Shen, H.C.; Ding, F.X.; Deng, Q.; Xu, S.; Chen, H.S.; Tong, X.; Tong, V.; Zhang, X.; Chen, Y.; Zhou, G.; Pai, L.Y.; Galicia, M. A.; Zhang, B.; Roy, S.; Tata, J. R.; Berger, J. P.; Colletti, S. L. Discovery of 3,3-disubstituted piperidine-derived trisubstituted ureas as highly potent soluble epoxide hydrolase inhibitors, Bioorg. Med. Chem. Lett., 2009, 19, 5314-5320.
79. Shen, H.C.; Ding, F.X.; Wang, X.; Deng, Q.; Zhang, X.; Chen, Y.; Zhou, G.; Xu, S.; Chen, H.S.; Tong, X.; Tong, V.; Mitra, K.; Kumar, S.; Tsai, C.; Stevenson, A. S.; Pai, L.Y.; Galicia, M. A.; Chen, X.; Soisson, S. M.; Roy, S.; Zhang, B.; Tata, J. R.; Berger, J. P.; Colletti, S. L, Discovery of a highly potent, selective and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement; J. Med. Chem., 2009, 52, 5009-5012; WO 011872, 2009.
80. Certikova, C.V, Walkowska, A, Jezierska, E. K.; Sadowskic, J.; Kujal, P.; Vernerová, Z.; Vaourková, Z.; Kopkan, L.; Kramer, H. J.; Falck, J.; Imig, J.D.; Hammock, B.D.; Vanourková, I.; Cervenka, L. Combined inhibition of 20-hydroxyeicosatetraenoic acid formation and of epoxyeicosatrienoic acids degradation attenuates hypertension and hypertension-induced end-organ damage in Ren-2 transgenic rats. Clin. Sci. [London], 2010, 118[10], 617-632.
81. Shen, H.C.; Ding, F.X.; Wang, S.; Xu, S.; Chen, H.S.; Tong, X.; Tong, V.; Mitra, K.; Kumar, S.; Zhang, X.; Chen, Y.; Zhou, G.; Pai, L.Y.; Galicia, M. A.; Chen, X.; Zheng, B.; Tata, J.R.; Berger, J. P.; Colletti, S.L. Discovery of spirocyclic secondary aminederived tertiary ureas as highly potent, selective and bioavailable soluble epoxide hydrolase inhibitors. Bioorg. Med. Chem. Lett., 2009, 19, 3398-3404.
82. Tanaka, D.; Tsuda, Y.;Shiyama, T.; Nishimura, T.; Chiyo, N.; Tominaga, Y.; Sawada, N.; Mimota, T.; Kusunose, N. A practical use of ligand efficiency indices out of the fragment based approach: Ligand efficiency guided lead identification of soluble epoxide hydrolase inhibitors. J. Med. Chem., 2011, 54, 851-857.
83. Sone, T.; Nakajima, T.; Takai, K. Preparation of bicyclic urea derivatives as soluble epoxide hydrolase inhibitors. PCT Int. Appl., 021645, 2011.
84. Aavula, B. R.; Anandan, S. K., Gless, R. D. Soluble epoxide hydrolase inhibitors. PCT Int. Appls., 129508, 2009; 035928, 2009.
85. Aavula, B. R.; Anandan, S. K., Gless, R. D. Soluble epoxide hydrolase inhibitors. U.S. Patent. Appls., 0270382, 2009; 02000467, 2008.
86. Lo, H.Y.; Man, C.A.; Fleck, R.W.; Farrow, N.A.; Ingraham, R. H.; Kukulka, A.; Pruodfoot, J. R.; Betageri, R.; Kirrane, T.; Patel, U.; Sharma, R.; Hoermann, M.A.; Kabcenell, A.; Lombaert, S. Substituted pyrazoles as novel sEH antagonist: Investigation of key binding interactions within the catalytic domain. Bioorg. Med. Chem. Lett., 2010, 20, 6379-6383.
87. Eldrup, A.B.; Soleymanzadeh, F.; Taylor, S.J.; Muegge, I.; Farrow, N.A.; Joseph, D.; McKellop, K.; Man, C.C.; Kukulka, A.; Lombaert, S.D. Structure based optimization of arylamides as inhibitors of soluble epoxide hydrolase. J. Med. Chem., 2009, 52, 5880-5895.
88. Ding, Y.; Thalji, R. K.; Marino, J. P. Preparation of 2-amino-1,3,5-triazine derivatives as soluble epoxide hydrolase (sEH) inhibitors and their use. PCT Int. Appl., 049157, 2009; 105968, 2008.
89. Marino, J. P.; McAtee, J. J. Preparation of pyrimidinylpiperidinylcarboxamides as sEH inhibitors. PCT Int. Appls. 097476, 2009; 049165, 2009; 097474, 2009.
90. Londregan, A. T.; Marino, J. P.; McAtee, J. J. Pyrimidine-amide derivatives as sEH inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases. PCT Int. Appl. 737772, 2009.
91. Tanaka, D. Diamide phenyl derivative and pharmaceutically acceptable salts thereof. PCT Int. Appl., 027888, 2011.
92. Feng, J.; Keung, W.; Lardy, M. Preparation of dioxo(tetrahydro)pyrimidinecarboxamide for use as sEH inhibitors. PCT Int. Appl., 129, 848, 2010.
93. Ota, T.; Takahashi, H.; Kakinuma, H, Busujima, T. Benzimidazole 5-carboxamide derivatives. PCT Int. Appl., 043653A1, 2007.
94. Ota, T.; Takahashi, H.; Kakinuma, H, Busujima, T. Anilide derivatives. Japan Patent Appl., 126454A1, 2007.
95. Xie, Y.; Liu, Y.; Gong, G.; Smith, D.H.; Yan, F.; Rinderspacher, A.; Feng, Y.; Zhu, Z.; L, X.; Deng, S-X.; Branden, l.; Vidovic, D.; Chung, C.; Schurer, S.; Morisseau, C.; Hammock, B.D.; Landry, D. W. Discovery of potent non-urea inhibitors of soluble epoxide hydrolase. Bioorg. Med. Chem. Lett., 2009, 19, 2354-2359.
96. Kim, I.H.; Park, Y.K.; Hammock, B.D.; Nish, K. Structure activity relationships of cycloalkylamide derivatives as inhibitors of the soluble epoxide hydrolase. J. Med. Chem., 2011, 54, 1752-1761.
97. Shen, H.C.; Ding, F.X.; Deng, Q.; Xu, S.; Tong, X.; Zhang, X.; Chen, Y.; Zhou, G.; Pai, L-Y.; Gallicia, M.A.; Roy, S.; Zhang, B.; Tata, J.R.; Berger, J.P.; Colletti, S.L. A strategy of employing aminoheterocycles as amide mimics to identify novel, potent and bioavailable soluble epoxide hydrolase inhibitors. Bioorg. Med. Chem. Lett., 2009, 19, 5716-5721.
98. Liu, J.Y.; Yang, J; Inceoglu, B.; Qiu, H.; Ulu, A.; Hwang, S-H.; Chiamvimonvat, N.; Hammock, B.D. Inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model. Biochemical Pharmacol., 2010, 79, 880-887.
99. The reagents of the University of California. Use of inhibition of soluble epoxide hydrolase to synergize activity of Cox and 5-Lox inhibition, US Patent 086,168, 2006, US Patent 0,178,347, 2006.
100. Hwang, S.H.; Wagner, K.M.; Morisseau; Liu, J-Y.; Dong, H.; Wecksler, A.T.; Hammock, B.D. Synthesis and structure activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase. J. Med. Chem., 2011, 54, 3037-3050.
101. Marino, J. P.; Brooks, C. A.; Eidam, P.; Mcatee, J. J. SEH and 11b-HSD1 dual inhibitors. PCT Int. Appls. 011917, 2010; 070497, 2009.
102. Lee, I. H.; Park, C. M.; Kim, S. H.; Chae, H.; Kim, S. Y. Preparation of ureas and related compounds for inhibiting soluble epoxide hydrolase (sEH) and 11b-hydroxy steroid dehydrogenase 1 (11b-HSD1). KR 066579, 2011.
103. Lee, I. H.; Park, C. M.; Kim, S. H.; Chae, H.; Kim, S. Y. Preparation of adamantane derivatives for inhibiting human soluble epoxide hydrolase (sEH) and 11b-hydroxy steroid dehydrogenase 1 (11b-HSD1). KR 013015, 2011.