Fluorine and chlorine substituted adamantyl-urea as molecular tools for inhibition of human soluble epoxide hydrolase with picomolar efficacy

References

• Gautheron J, Jéru I. The multifaceted role of epoxide hydrolases in human health and disease. Int J Mol Sci. 2020;22(1):13.
   PubMed Web of Science ®Google Scholar
• Morisseau C, Hammock BD. Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol. 2013;53(1):37–58.
   PubMed Web of Science ®Google Scholar
• Oni-Orisan A, Alsaleh N, Lee CR, Seubert JM. Epoxyeicosatrienoic acids and cardioprotection: the road to translation. J Mol Cell Cardiol. 2014;74:199–208.
   PubMed Web of Science ®Google Scholar
• Tacconelli S, Patrignani P. Inside epoxyeicosatrienoic acids and cardiovascular disease. Front Pharmacol. 2014;5:239.
   PubMed Web of Science ®Google Scholar
• Huang H, Al-Shabrawey M, Wang MH. Cyclooxygenase- and cytochrome P450-derived eicosanoids in stroke. Prostaglandins Other Lipid Mediat. 2016;122:45–53.
   PubMed Web of Science ®Google Scholar
• Anandan S-K, Webb HK, Chen D, Wang Y-X, Aavula BR, Cases S, Cheng Y, Do ZN, Mehra U, Tran V, et al. 1-(1-Acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia. Bioorg Med Chem Lett. 2011;21(3):983–988.
   PubMed Web of Science ®Google Scholar
• Hammock BD, McReynolds CB, Wagner K, Buckpitt A, Cortes-Puch I, Croston G, Lee KSS, Yang J, Schmidt WK, Hwang SH. Movement to the clinic of soluble epoxide hydrolase inhibitor EC5026 as an analgesic for neuropathic pain and for use as a nonaddictive opioid alternative. J Med Chem. 2021;64(4):1856–1872.
   PubMed Web of Science ®Google Scholar
• Borsini A. The role of soluble epoxide hydrolase and its inhibitors in depression. Brain Behav Immun Health. 2021;16 (16):100325.
   PubMedGoogle Scholar
• Shan J, Hashimoto K. Soluble epoxide hydrolase as a therapeutic target for neuropsychiatric disorders. Int J Mol Sci. 2022;23(9):4951.
   PubMed Web of Science ®Google Scholar
• Nazari M, Rezaee E, Tabatabai SA. A comprehensive review of soluble epoxide hydrolase inhibitors evaluating their structure-activity relationship. Mini Rev Med Chem. 2023;23(1):99–117.
   PubMed Web of Science ®Google Scholar
• Chen D, Whitcomb R, MacIntyre E, Tran V, Do ZN, Sabry J, Patel DV, Anandan SK, Gless R, Webb HK. Pharmacokinetics and pharmacodynamics of AR9281, an inhibitor of soluble epoxide hydrolase, in single- and multiple-dose studies in healthy human subjects. J Clin Pharmacol. 2012;52(3):319–328.
   PubMed Web of Science ®Google Scholar
• Hwang SH, Tsai H-J, Liu J-Y, Morisseau C, Hammock BD. Orally bioavailable potent soluble epoxide hydrolase inhibitors. J Med Chem. 2007;50(16):3825–3840.
   PubMed Web of Science ®Google Scholar
• Burmistrov V, Morisseau C, Harris TR, Butov G, Hammock BD. Effects of adamantane alterations on soluble epoxide hydrolase inhibition potency, physical properties and metabolic stability. Bioorg Chem. 2018;76:510–527.
   PubMed Web of Science ®Google Scholar
• Burmistrov VV, Butov GM, Karlov DS, Palyulin VA, Zefirov NS, Morisseau C, Hammock BD. Synthesis and properties of diadamantyl-containing symmetric diureas as target-oriented inhibitors of human soluble epoxide hydrolase. Russ J Bioorg Chem. 2016;42(4):404–414.
   Web of Science ®Google Scholar
• Wanka L, Iqbal K, Schreiner PR. The lipophilic bullet hits the targets: medicinal chemistry of adamantane derivatives. Chem Rev. 2013;113(5):3516–3604.
   PubMed Web of Science ®Google Scholar
• Liu J-Y, Tsai H-J, Morisseau C, Lango J, Hwang SH, Watanabe T, Kim I-H, Hammock BD. In vitro and in vivo metabolism of N-adamantyl substituted urea-based soluble epoxide hydrolase inhibitors. Biochem Pharmacol. 2015;98(4):718–731.
   PubMed Web of Science ®Google Scholar
• Du F, Sun W, Morisseau C, Hammock BD, Bao X, Liu Q, Wang C, Zhang T, Yang H, Zhou J, et al. Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis. Eur J Med Chem. 2021;223:113678.
   PubMed Web of Science ®Google Scholar
• Burmistrov V, Morisseau C, Karlov D, Pitushkin D, Vernigora A, Rasskazova E, Butov GM, Hammock BD. Bioisosteric substitution of adamantane with bicyclic lipophilic groups improves water solubility of human soluble epoxide hydrolase inhibitors. Bioorg Med Chem Lett. 2020;30(18):127430.
   PubMed Web of Science ®Google Scholar
• Codony S, Calvó-Tusell C, Valverde E, Osuna S, Morisseau C, Loza MI, Brea J, Pérez C, Rodríguez-Franco MI, Pizarro-Delgado J, et al. From the design to the in vivo evaluation of benzohomoadamantane-derived soluble epoxide hydrolase inhibitors for the treatment of acute pancreatitis. J Med Chem. 2021;64(9):5429–5446.
   PubMed Web of Science ®Google Scholar
• Gillis EP, Eastman KJ, Hill MD, Donnelly DJ, Meanwell NA. Applications of fluorine in medicinal chemistry. J Med Chem. 2015;58(21):8315–8359.
   PubMed Web of Science ®Google Scholar
• Meanwell NA. Fluorine and fluorinated motifs in the design and application of bioisosteres for drug design. J Med Chem. 2018;61(14):5822–5880.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Next generation of fluorine-containing pharmaceuticals, compounds currently in phase II–III clinical trials of major pharmaceutical companies: new structural trends and therapeutic areas. Chem Rev. 2016;116(2):422–518.
   PubMed Web of Science ®Google Scholar
• Danilov DV, Burmistrov VV, Kuznetsov YP, D’yachenko VS, Rasskazova EV, Butov GM. Synthesis and properties of N,N′-disubstituted ureas and their isosteric analogs containing polycyclic fragments: VIII. Synthesis and properties of N-[(3-chloroadamantan-1-yl)methyl]-N′-(fluoro, chlorophenyl)ureas and symmetrical bis-ureas. Russ J Org Chem. 2021; 57(3):327–337.
   Web of Science ®Google Scholar
• Danilov DV, D’yachenko VS, Burmistrov VV, Butov GM, Novakov IA. Synthesis and properties of 1-[(3-fluoroadamantan-1-yl)methyl]-3-R-ureas and 1,1′-(alkan-1,n-diyl)bis{3-[(3-fluoroadamantan-1-yl)methyl]ureas} as promising soluble epoxide hydrolase inhibitors. Russ Chem Bull. 2022;71(1):107–113.
   Web of Science ®Google Scholar
• Delaney JS. ESOL: estimating aqueous solubility directly from molecular structure. J Chem Inf Comput Sci. 2004;44(3):1000–1005.
   PubMedGoogle Scholar
• Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1):42717.
   PubMed Web of Science ®Google Scholar
• Jones PD, Wolf NM, Morisseau C, Whetstone P, Hock B, Hammock BD. Fluorescent substrates for soluble epoxide hydrolase and application to inhibition studies. Anal Biochem. 2005;343(1):66–75.
   PubMed Web of Science ®Google Scholar
• Ulu A, Appt S, Morisseau C, Hwang SH, Jones PD, Rose TE, Dong H, Lango J, Yang J, Tsai HJ, et al. Pharmacokinetics and in vivo potency of soluble epoxide hydrolase inhibitors in cynomolgus monkeys. Br J Pharmacol. 2012;165(5):1401–1412.
   PubMed Web of Science ®Google Scholar
• Imai YN, Inoue Y, Nakanishi I, Kitaura K. Cl-pi interactions in protein-ligand complexes. Protein Sci. 2008;17(7):1129–1137.
   PubMed Web of Science ®Google Scholar
• Li P, Maier JM, Vik EC, Yehl CJ, Dial BE, Rickher AE, Smith MD, Pellechia PJ, Shimizu KD. Stabilizing fluorine-π interactions. Angew Chem Int Ed Engl. 2017;56(25):7209–7212.
   PubMed Web of Science ®Google Scholar
• Beetham JK, Tian TG, Hammock BD. cDNA cloning and expression of a soluble epoxide hydrolase from human liver. Arch Biochem Biophys. 1993;305(1):197–201.
   PubMed Web of Science ®Google Scholar
• Wixtrom RN, Silva MH, Hammock BD. Affinity purification of cytosolic epoxide hydrolase using derivatized epoxy-activated Sepharose gels. Anal Biochem. 1988;169(1):71–80.
   PubMed Web of Science ®Google Scholar
• Öster L, Tapani S, Xue Y, Käck H. Successful generation of structural information for fragment-based drug discovery. Drug Discov Today. 2015;20(9):1104–1111.
   PubMed Web of Science ®Google Scholar
• Huang J, MacKerell AD. CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data. J Comput Chem. 2013;34(25):2135–2145.
   PubMed Web of Science ®Google Scholar
• Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I, et al. CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem. 2010;31(4):671–690.
   PubMed Web of Science ®Google Scholar
• Kim S, Lee J, Jo S, Brooks CL, Lee HS, Im W. CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small molecules. J Comput Chem. 2017;38(21):1879–1886.
   PubMed Web of Science ®Google Scholar
• Jo S, Kim T, Iyer VG, Im W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J Comput Chem. 2008;29(11):1859–1865.
   PubMed Web of Science ®Google Scholar
• Roe DR, Cheatham TE. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput. 2013;9(7):3084–3095.
   PubMed Web of Science ®Google Scholar
• Salomon-Ferrer R, Case DA, Walker RC. An overview of the AMBER biomolecular simulation package. WIREs Comput Mol Sci. 2013;3(2):198–210.
   Web of Science ®Google Scholar
• Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera – a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–1612.
   PubMed Web of Science ®Google Scholar
• Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455–461.
   PubMed Web of Science ®Google Scholar
• Dassault Systèmes BIOVIA. Discovery studio modeling environment, release 2023. San Diego, CA: Dassault Systèmes, 2023.
   Google Scholar