{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:16:51Z","timestamp":1788261411324,"version":"build-2803163510"},"reference-count":71,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["SC2GM135020"],"award-info":[{"award-number":["SC2GM135020"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE1726903"],"award-info":[{"award-number":["CHE1726903"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P42 ES004699"],"award-info":[{"award-number":["P42 ES004699"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R35ES030443"],"award-info":[{"award-number":["R35ES030443"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry"],"published-print":{"date-parts":[[2021,12]]},"DOI":"10.1016\/j.bmc.2021.116507","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T20:54:57Z","timestamp":1636577697000},"page":"116507","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"special_numbering":"C","title":["Further exploration of the structure-activity relationship of dual soluble epoxide hydrolase\/fatty acid amide hydrolase inhibitors"],"prefix":"10.1016","volume":"51","author":[{"given":"Stephanie","family":"Wilt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Kodani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Valencia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula K.","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Quintana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Morisseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Hammock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Kandasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stevan","family":"Pecic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2021.116507_b0005","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev.med.49.1.123","article-title":"Chronic pain","volume":"49","author":"Russo","year":"1998","journal-title":"Annu Rev Med"},{"issue":"3","key":"10.1016\/j.bmc.2021.116507_b0010","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/fampra\/18.3.292","article-title":"The impact of chronic pain in the community","volume":"18","author":"Smith","year":"2001","journal-title":"Fam Pract"},{"issue":"6","key":"10.1016\/j.bmc.2021.116507_b0015","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"issue":"6","key":"10.1016\/j.bmc.2021.116507_b0020","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1159\/000452591","article-title":"Triptolide attenuates inflammatory response in membranous glomerulo-nephritis rat via downregulation of NF-\u03baB signaling pathway","volume":"41","author":"Zhou","year":"2016","journal-title":"Kidney Blood Press Res"},{"issue":"7","key":"10.1016\/j.bmc.2021.116507_b0025","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nrn1700","article-title":"Role of the immune system in chronic pain","volume":"6","author":"Marchand","year":"2005","journal-title":"Nat Rev Neurosci"},{"issue":"11","key":"10.1016\/j.bmc.2021.116507_b0030","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/nm.2234","article-title":"Interactions between the immune and nervous systems in pain","volume":"16","author":"Ren","year":"2010","journal-title":"Nat Med"},{"issue":"6A","key":"10.1016\/j.bmc.2021.116507_b0035","doi-asserted-by":"crossref","first-page":"27S","DOI":"10.1016\/S0002-9343(99)00365-4","article-title":"Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs)","volume":"107","author":"Rainsford","year":"1999","journal-title":"Am J Med"},{"issue":"3","key":"10.1016\/j.bmc.2021.116507_b0040","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/eji.201445222","article-title":"NSAIDs: learning new tricks from old drugs","volume":"45","author":"D\u00edaz-Gonz\u00e1lez","year":"2015","journal-title":"Eur J Immunol"},{"issue":"10","key":"10.1016\/j.bmc.2021.116507_b0045","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nrd2875","article-title":"Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases","volume":"8","author":"Imig","year":"2009","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0050","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1146\/annurev-pharmtox-011112-140244","article-title":"Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health","volume":"53","author":"Morisseau","year":"2013","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"2","key":"10.1016\/j.bmc.2021.116507_b0055","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.gene.2013.05.008","article-title":"Soluble epoxide hydrolase: gene structure, expression and deletion","volume":"526","author":"Harris","year":"2013","journal-title":"Gene"},{"issue":"4","key":"10.1016\/j.bmc.2021.116507_b0060","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1177\/002215540405200403","article-title":"Distribution of soluble epoxide hydrolase and of cytochrome P450 2C8, 2C9, and 2J2 in human tissues","volume":"52","author":"Enayetallah","year":"2004","journal-title":"J Histochem Cytochem"},{"key":"10.1016\/j.bmc.2021.116507_b0065","doi-asserted-by":"crossref","first-page":"554961","DOI":"10.3389\/fphar.2020.554961","article-title":"Multi-target approaches in metabolic syndrome","volume":"11","author":"Lillich","year":"2020","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.bmc.2021.116507_b0070","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.biochi.2019.01.020","article-title":"Role of epoxy-fatty acids and epoxide hydrolases in the pathology of neuro-inflammation","volume":"159","author":"Kodani","year":"2019","journal-title":"Biochimie"},{"issue":"28","key":"10.1016\/j.bmc.2021.116507_b0075","doi-asserted-by":"crossref","first-page":"9772","DOI":"10.1073\/pnas.0503279102","article-title":"Soluble epoxide hydrolase is a therapeutic target for acute inflammation","volume":"102","author":"Schmelzer","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.bmc.2021.116507_b0080","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.pharmthera.2017.06.006","article-title":"Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases","volume":"180","author":"Wagner","year":"2017","journal-title":"Pharmacol Ther"},{"issue":"11","key":"10.1016\/j.bmc.2021.116507_b0085","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.drudis.2015.07.017","article-title":"A multimodal disease modifying approach to treat neuropathic pain\u2013inhibition of soluble epoxide hydrolase (sEH)","volume":"20","author":"Pillarisetti","year":"2015","journal-title":"Drug Discov Today"},{"issue":"24","key":"10.1016\/j.bmc.2021.116507_b0090","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1016\/j.lfs.2006.07.031","article-title":"Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain","volume":"79","author":"Inceoglu","year":"2006","journal-title":"Life Sci"},{"issue":"4","key":"10.1016\/j.bmc.2021.116507_b0095","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S1367-5931(03)00079-6","article-title":"Fatty acid amide hydrolase: an emerging therapeutic target in the endocannabinoid system","volume":"7","author":"Cravatt","year":"2003","journal-title":"Curr Opin Chem Biol"},{"key":"10.1016\/j.bmc.2021.116507_b0100","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev.biochem.74.082803.133450","article-title":"Structure and function of fatty acid amide hydrolase","volume":"74","author":"McKinney","year":"2005","journal-title":"Annu Rev Biochem"},{"issue":"3","key":"10.1016\/j.bmc.2021.116507_b0105","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0304-3959(01)00454-7","article-title":"CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain","volume":"96","author":"Clayton","year":"2002","journal-title":"Pain"},{"issue":"3","key":"10.1016\/j.bmc.2021.116507_b0110","doi-asserted-by":"crossref","first-page":"H1344","DOI":"10.1152\/ajpheart.00537.2004","article-title":"Endothelium-derived 2-arachidonylglycerol: an intermediate in vasodilatory eicosanoid release in bovine coronary arteries","volume":"288","author":"Gauthier","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"3-4","key":"10.1016\/j.bmc.2021.116507_b0115","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.prostaglandins.2009.06.004","article-title":"Epoxyeicosanoid signaling in CNS function and disease","volume":"91","author":"Iliff","year":"2010","journal-title":"Prostaglandins Other Lipid Mediat"},{"issue":"9","key":"10.1016\/j.bmc.2021.116507_b0120","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/j.pain.2012.04.020","volume":"153","author":"Huggins","year":"2012","journal-title":"Pain"},{"issue":"4","key":"10.1016\/j.bmc.2021.116507_b0125","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1124\/mol.108.053439","article-title":"A cytochrome P450-derived epoxygenated metabolite of anandamide is a potent cannabinoid receptor 2-selective agonist","volume":"75","author":"Snider","year":"2009","journal-title":"Mol Pharmacol"},{"issue":"30","key":"10.1016\/j.bmc.2021.116507_b0130","doi-asserted-by":"crossref","first-page":"E6034","DOI":"10.1073\/pnas.1610325114","article-title":"Anti-inflammatory \u03c9-3 endocannabinoid epoxides","volume":"114","author":"McDougle","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.bmc.2021.116507_b0135","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.phrs.2015.04.001","article-title":"Peripheral FAAH and soluble epoxide hydrolase inhibitors are synergistically antinociceptive","volume":"97","author":"Sasso","year":"2015","journal-title":"Pharmacol Res"},{"issue":"2","key":"10.1016\/j.bmc.2021.116507_b0140","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1021\/acs.jmedchem.8b00760","article-title":"Polypharmacology by design: a medicinal chemist's perspective on multitargeting compounds","volume":"62","author":"Proschak","year":"2019","journal-title":"J Med Chem"},{"issue":"15","key":"10.1016\/j.bmc.2021.116507_b0145","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S1359-6446(04)03163-0","article-title":"From magic bullets to designed multiple ligands","volume":"9","author":"Morphy","year":"2004","journal-title":"Drug Discov Today"},{"issue":"12","key":"10.1016\/j.bmc.2021.116507_b0150","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1002\/cmdc.201500507","article-title":"The molecular basis for dual fatty acid amide hydrolase (FAAH)\/cyclooxygenase (COX) inhibition","volume":"11","author":"Palermo","year":"2016","journal-title":"ChemMedChem"},{"key":"10.1016\/j.bmc.2021.116507_b0155","doi-asserted-by":"crossref","first-page":"112662","DOI":"10.1016\/j.ejmech.2020.112662","article-title":"Discovery of novel urea-diarylpyrazole hybrids as dual COX-2\/sEH inhibitors with improved anti-inflammatory activity and highly reduced cardiovascular risks","volume":"205","author":"Abdelazeem","year":"2020","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmc.2021.116507_b0160","doi-asserted-by":"crossref","first-page":"104165","DOI":"10.1016\/j.bioorg.2020.104165","article-title":"Development of multitarget inhibitors for the treatment of pain: design, synthesis, biological evaluation and molecular modeling studies","volume":"103","author":"Wilt","year":"2020","journal-title":"Bioorg Chem"},{"issue":"2","key":"10.1016\/j.bmc.2021.116507_b0165","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.bmcl.2012.11.084","article-title":"Synthesis and structure\u2013activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors","volume":"23","author":"Pecic","year":"2013","journal-title":"Bioorg Med Chem Lett"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0170","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.bmcl.2011.10.074","article-title":"Design, synthesis and evaluation of non-urea inhibitors of soluble epoxide hydrolase","volume":"22","author":"Pecic","year":"2012","journal-title":"Bioorg Med Chem Lett"},{"issue":"6","key":"10.1016\/j.bmc.2021.116507_b0175","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/cts.12577","article-title":"The current status of drug discovery and development as originated in United States academia: the influence of industrial and academic collaboration on drug discovery and development","volume":"11","author":"Takebe","year":"2018","journal-title":"Clin Transl Sci"},{"issue":"7","key":"10.1016\/j.bmc.2021.116507_b0180","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/d41573-019-00074-z","article-title":"Trends in clinical success rates and therapeutic focus","volume":"18","author":"Dowden","year":"2019","journal-title":"Nat Rev Drug Discov"},{"issue":"5","key":"10.1016\/j.bmc.2021.116507_b0185","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/cbdd.13670","article-title":"Design, microwave-assisted synthesis, biological evaluation and molecular modeling studies of 4-phenylthiazoles as potent fatty acid amide hydrolase inhibitors","volume":"95","author":"Wilt","year":"2020","journal-title":"Chem Biol Drug Des"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0190","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1021\/jm801042a","article-title":"Synthesis and evaluation of benzothiazole-based analogues as novel, potent, and selective fatty acid amide hydrolase inhibitors","volume":"52","author":"Wang","year":"2009","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2021.116507_b0195","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.prostaglandins.2018.02.004","article-title":"Novel piperidine-derived amide sEH inhibitors as mediators of lipid metabolism with improved stability","volume":"136","author":"Pecic","year":"2018","journal-title":"Prostaglandins Other Lipid Mediat"},{"issue":"16","key":"10.1016\/j.bmc.2021.116507_b0200","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.1016\/j.bmcl.2011.06.096","article-title":"The discovery and development of inhibitors of fatty acid amide hydrolase (FAAH)","volume":"21","author":"Otrubova","year":"2011","journal-title":"Bioorg Med Chem Lett"},{"issue":"20","key":"10.1016\/j.bmc.2021.116507_b0205","doi-asserted-by":"crossref","first-page":"127463","DOI":"10.1016\/j.bmcl.2020.127463","article-title":"Heteroarylureas with fused bicyclic diamine cores as inhibitors of fatty acid amide hydrolase","volume":"30","author":"Keith","year":"2020","journal-title":"Bioorg Med Chem Lett"},{"issue":"4","key":"10.1016\/j.bmc.2021.116507_b0210","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.chembiol.2009.02.013","article-title":"Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain","volume":"16","author":"Ahn","year":"2009","journal-title":"Chem Biol"},{"issue":"4","key":"10.1016\/j.bmc.2021.116507_b0215","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.bmcl.2018.01.003","article-title":"Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase","volume":"28","author":"Kodani","year":"2018","journal-title":"Bioorg Med Chem Lett"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0220","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ab.2005.03.041","article-title":"Fluorescent substrates for soluble epoxide hydrolase and application to inhibition studies","volume":"343","author":"Jones","year":"2005","journal-title":"Anal Biochem"},{"issue":"16","key":"10.1016\/j.bmc.2021.116507_b0225","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1021\/jm070270t","article-title":"Orally bioavailable potent soluble epoxide hydrolase inhibitors","volume":"50","author":"Hwang","year":"2007","journal-title":"J Med Chem"},{"issue":"10","key":"10.1016\/j.bmc.2021.116507_b0230","doi-asserted-by":"crossref","first-page":"14076","DOI":"10.1021\/acsomega.8b01625","article-title":"Design and potency of dual soluble epoxide hydrolase\/fatty acid amide hydrolase inhibitors","volume":"3","author":"Kodani","year":"2018","journal-title":"ACS Omega"},{"key":"10.1016\/j.bmc.2021.116507_b0235","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jmgm.2015.01.009","article-title":"Comparing sixteen scoring functions for predicting biological activities of ligands for protein targets","volume":"57","author":"Xu","year":"2015","journal-title":"J Mol Graph Model"},{"issue":"4","key":"10.1016\/j.bmc.2021.116507_b0240","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nprot.2017.114","article-title":"Assessing protein\u2013ligand interaction scoring functions with the CASF-2013 benchmark","volume":"13","author":"Li","year":"2018","journal-title":"Nat Protoc"},{"issue":"3","key":"10.1016\/j.bmc.2021.116507_b0245","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1006\/jmbi.1994.1052","article-title":"Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins","volume":"235","author":"Abagyan","year":"1994","journal-title":"J Mol Biol"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0250","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10822-018-0139-5","article-title":"Hybrid receptor structure\/ligand-based docking and activity prediction in ICM: development and evaluation in D3R Grand Challenge 3","volume":"33","author":"Lam","year":"2019","journal-title":"J Comput Aided Mol Des"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0255","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10822-017-0058-x","article-title":"Ligand-biased ensemble receptor docking (LigBEnD): a hybrid ligand\/receptor structure-based approach","volume":"32","author":"Lam","year":"2018","journal-title":"J Comput Aided Mol Des"},{"issue":"7","key":"10.1016\/j.bmc.2021.116507_b0260","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1021\/acs.jcim.8b00228","article-title":"Comparative evaluation of covalent docking tools","volume":"58","author":"Scarpino","year":"2018","journal-title":"J Chem Inf Model"},{"issue":"4","key":"10.1016\/j.bmc.2021.116507_b0265","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jmb.2010.05.034","article-title":"Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation","volume":"400","author":"Mileni","year":"2010","journal-title":"J Mol Biol"},{"issue":"7","key":"10.1016\/j.bmc.2021.116507_b0270","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1517\/17460440903018857","article-title":"Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders","volume":"4","author":"Ahn","year":"2009","journal-title":"Expert Opin Drug Discov"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0275","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1056-8719(00)00107-6","article-title":"Drug-like properties and the causes of poor solubility and poor permeability","volume":"44","author":"Lipinski","year":"2000","journal-title":"J Pharmacol Toxicol Methods"},{"issue":"1-3","key":"10.1016\/j.bmc.2021.116507_b0280","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv Drug Deliv Rev"},{"issue":"12","key":"10.1016\/j.bmc.2021.116507_b0285","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2021.116507_b0290","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.addr.2016.05.007","article-title":"BDDCS, the rule of 5 and drugability","volume":"101","author":"Benet","year":"2016","journal-title":"Adv Drug Deliv Rev"},{"issue":"2","key":"10.1016\/j.bmc.2021.116507_b0295","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1517\/17425255.1.2.175","article-title":"Caco-2 cell permeability assays to measure drug absorption","volume":"1","author":"van Breemen","year":"2005","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"7","key":"10.1016\/j.bmc.2021.116507_b0300","doi-asserted-by":"crossref","first-page":"459","DOI":"10.2170\/physiolsci.RV011408","article-title":"In silico prediction of the chemical block of human ether-a-go-go-related gene (hERG) K+ current","volume":"58","author":"Inanobe","year":"2008","journal-title":"J Physiol Sci"},{"issue":"11","key":"10.1016\/j.bmc.2021.116507_b0305","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2174\/1568026614666140506124442","article-title":"Tuning HERG out: antitarget QSAR models for drug development","volume":"14","author":"Braga","year":"2014","journal-title":"Curr Top Med Chem"},{"issue":"W1","key":"10.1016\/j.bmc.2021.116507_b0310","doi-asserted-by":"crossref","first-page":"W257","DOI":"10.1093\/nar\/gky318","article-title":"ProTox-II: a webserver for the prediction of toxicity of chemicals","volume":"46","author":"Banerjee","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"Supp C","key":"10.1016\/j.bmc.2021.116507_b0315","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0304-3959(77)90130-0","article-title":"The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats","volume":"4","author":"Dubuisson","year":"1977","journal-title":"Pain"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0320","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0304-3959(87)90088-1","article-title":"The formalin test in mice: dissociation between inflammatory and non-inflammatory pain","volume":"30","author":"Hunskaar","year":"1987","journal-title":"Pain"},{"issue":"3","key":"10.1016\/j.bmc.2021.116507_b0325","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0304-3959(97)03366-6","article-title":"A new automated method of pain scoring in the formalin test in rats","volume":"71","author":"Jourdan","year":"1997","journal-title":"Pain"},{"key":"10.1016\/j.bmc.2021.116507_b0330","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2147\/JPR.S241893","article-title":"Inhibition of the soluble epoxide hydrolase as an analgesic strategy: a review of preclinical evidence","volume":"14","author":"Wang","year":"2021","journal-title":"J Pain Res"},{"issue":"Suppl 1","key":"10.1016\/j.bmc.2021.116507_b0335","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1097\/j.pain.0000000000002268","article-title":"Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies","volume":"162","author":"Finn","year":"2021","journal-title":"Pain"},{"issue":"6","key":"10.1016\/j.bmc.2021.116507_b0340","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2174\/187152709789824660","article-title":"The endocannabinoid system and pain","volume":"8","author":"Guindon","year":"2009","journal-title":"CNS Neurol Disord: Drug Targets"},{"issue":"10","key":"10.1016\/j.bmc.2021.116507_b0345","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/nn.2632","article-title":"Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism","volume":"13","author":"Clapper","year":"2010","journal-title":"Nat Neurosci"},{"issue":"21","key":"10.1016\/j.bmc.2021.116507_b0350","doi-asserted-by":"crossref","first-page":"12198","DOI":"10.1073\/pnas.96.21.12198","article-title":"Pain modulation by release of the endogenous cannabinoid anandamide","volume":"96","author":"Walker","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"10.1016\/j.bmc.2021.116507_b0355","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1747-0285.2007.00605.x","article-title":"Atomic property fields: generalized 3D pharmacophoric potential for automated ligand superposition, pharmacophore elucidation and 3D QSAR","volume":"71","author":"Totrov","year":"2008","journal-title":"Chem Biol Drug Des"}],"container-title":["Bioorganic &amp; Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089621005150?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089621005150?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:29:16Z","timestamp":1778574556000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089621005150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":71,"alternative-id":["S0968089621005150"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2021.116507","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Further exploration of the structure-activity relationship of dual soluble epoxide hydrolase\/fatty acid amide hydrolase inhibitors","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2021.116507","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"116507"}}