{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:02:18Z","timestamp":1784556138218,"version":"3.55.0"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T00:00:00Z","timestamp":1651881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry"],"published-print":{"date-parts":[[2022,7]]},"DOI":"10.1016\/j.bmc.2022.116804","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T11:22:45Z","timestamp":1651922565000},"page":"116804","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["2-Alkyl substituted benzimidazoles as a new class of selective AT2 receptor ligands"],"prefix":"10.1016","volume":"66","author":[{"given":"Tamal","family":"Roy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia N.","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greeshma","family":"Gopalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Gising","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Hallberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Larhed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2022.116804_b0005","doi-asserted-by":"crossref","first-page":"5995","DOI":"10.1021\/jm049715t","article-title":"Design, synthesis, and biological evaluation, of the first selective nonpeptide AT2 receptor agonist","volume":"47","author":"Wan","year":"2004","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0010","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3389\/fphar.2017.00564","article-title":"Anti-fibrotic Potential of AT2 Receptor Agonists","volume":"8","author":"Wang","year":"2017","journal-title":"Front Pharmacol."},{"key":"10.1016\/j.bmc.2022.116804_b0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2021.101152","article-title":"Seven days treatment with the angiotensin II type 2 receptor agonist C21 in hospitalized COVID-19 patients; a placebo-controlled randomised multi-centre double-blind phase 2 trial","volume":"41","author":"Tornling","year":"2021","journal-title":"EClinicalMedicine."},{"key":"10.1016\/j.bmc.2022.116804_b0020","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/med.21449","article-title":"Small-molecule AT2 receptor agonists","volume":"38","author":"Hallberg","year":"2018","journal-title":"Med Res Rev."},{"issue":"69\u201382","key":"10.1016\/j.bmc.2022.116804_b0025","article-title":"Nonpeptide AT2 Receptor Agonists","volume":"51","author":"Larhed","year":"2016","journal-title":"In: Medicinal Chemistry Reviews."},{"key":"10.1016\/j.bmc.2022.116804_b0030","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1097\/j.pain.0000000000001361","article-title":"Neuroprotective effect of angiotensin II type 2 receptor stimulation in vincristine-induced mechanical allodynia","volume":"159","author":"Bessaguet","year":"2018","journal-title":"Pain"},{"key":"10.1016\/j.bmc.2022.116804_b0035","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/mus.21747","article-title":"Broadening the spectrum of controls for skin biopsy in painful neuropathies","volume":"42","author":"Herrmann","year":"2010","journal-title":"Muscle Nerve."},{"key":"10.1016\/j.bmc.2022.116804_b0040","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/S0140-6736(13)62337-5","article-title":"EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial","volume":"383","author":"Rice","year":"2014","journal-title":"Lancet"},{"issue":"Suppl 1","key":"10.1016\/j.bmc.2022.116804_b0045","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1097\/j.pain.0000000000000369","article-title":"Selective small molecule angiotensin II type 2 receptor antagonists for neuropathic pain: preclinical and clinical studies","volume":"157","author":"Smith","year":"2016","journal-title":"Pain"},{"key":"10.1016\/j.bmc.2022.116804_b0050","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1097\/j.pain.0000000000002252","article-title":"Efficacy and safety of EMA401 in peripheral neuropathic pain: results of 2 randomised. double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy","volume":"162","author":"Rice","year":"2021","journal-title":"Pain"},{"key":"10.1016\/j.bmc.2022.116804_b0055","first-page":"R820","article-title":"Discovery of L-162,313: a nonpeptide that mimics the biological actions of angiotensin II","volume":"268","author":"Kivlighn","year":"1995","journal-title":"Am J Physiol."},{"key":"10.1016\/j.bmc.2022.116804_b0060","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1074\/jbc.270.4.1493","article-title":"Non-peptide angiotensin agonist. Functional and molecular interaction with the AT1 receptor","volume":"270","author":"Perlman","year":"1995","journal-title":"J Biol Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0065","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1021\/jm031031i","article-title":"First Reported Nonpeptide AT1 Receptor Agonist (L-162,313) Acts as an AT2 Receptor Agonist in Vivo","volume":"47","author":"Wan","year":"2004","journal-title":"J Med Chem."},{"issue":"24","key":"10.1016\/j.bmc.2022.116804_b0070","doi-asserted-by":"crossref","first-page":"7160","DOI":"10.1021\/jm0606185","article-title":"Selective angiotensin II AT2 receptor agonists: Arylbenzylimidazole structure-activity relationships","volume":"49","author":"Wu","year":"2006","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0075","doi-asserted-by":"crossref","first-page":"7166","DOI":"10.1016\/j.bmc.2007.07.026","article-title":"Selective angiotensin II AT2 receptor agonists devoid of the imidazole ring system","volume":"15","author":"Murugaiah","year":"2007","journal-title":"Bioorg Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0080","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1021\/jm0613469","article-title":"Synthesis of a new class of druglike angiotensin II C-terminal mimics with affinity for the AT2 receptor","volume":"50","author":"Georgsson","year":"2007","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0085","doi-asserted-by":"crossref","first-page":"6841","DOI":"10.1016\/j.bmc.2008.05.066","article-title":"Selective angiotensin II AT2 receptor agonists: Benzamide structure\u2013activity relationships","volume":"16","author":"Wallinder","year":"2008","journal-title":"Bioorg Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0090","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1016\/j.bmc.2010.03.064","article-title":"Selective angiotensin II AT2 receptor agonists with reduced CYP 450 inhibition","volume":"18","author":"Mahalingam","year":"2010","journal-title":"Bioorg Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0095","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1021\/ml500427r","article-title":"Interconversion of Functional Activity by Minor Structural Alterations in Nonpeptide AT2 Receptor Ligands","volume":"6","author":"Wallinder","year":"2014","journal-title":"ACS Med Chem Lett."},{"key":"10.1016\/j.bmc.2022.116804_b0100","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1039\/C9MD00402E","article-title":"High affinity rigidified AT2 receptor ligands with indane scaffolds","volume":"10","author":"Wallinder","year":"2019","journal-title":"Medchemcomm."},{"key":"10.1016\/j.bmc.2022.116804_b0105","doi-asserted-by":"crossref","first-page":"809","DOI":"10.2174\/1389203718666170203150344","article-title":"Angiotensin Peptides as AT2 Receptor Agonists","volume":"18","author":"Hallberg","year":"2017","journal-title":"Curr Protein Pept Sci."},{"key":"10.1016\/j.bmc.2022.116804_b0110","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1021\/ml500278g","article-title":"Saralasin and Sarile Are AT2 Receptor Agonists","volume":"5","author":"Guimond","year":"2014","journal-title":"ACS Med Chem Lett."},{"key":"10.1016\/j.bmc.2022.116804_b0115","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.bmcl.2017.11.042","article-title":"A convenient transesterification method for synthesis of AT2 receptor ligands with improved stability in human liver microsomes","volume":"28","author":"Wannberg","year":"2018","journal-title":"Bioorg Med Chem Lett."},{"key":"10.1016\/j.bmc.2022.116804_b0120","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1021\/jm070680h","article-title":"Two-Carbon-Elongated HIV-1 Protease Inhibitors with a Tertiary-Alcohol-Containing Transition-State Mimic\u22a5","volume":"51","author":"Wu","year":"2008","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0125","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1124\/mol.51.2.301","article-title":"Dual Agonistic and Antagonistic Property of Nonpeptide Angiotensin AT1 Ligands: Susceptibility to Receptor Mutations","volume":"51","author":"Perlman","year":"1997","journal-title":"Mol Pharmacol."},{"key":"10.1016\/j.bmc.2022.116804_b0130","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S0026-895X(25)09488-X","article-title":"Subclasses of angiotensin II binding sites and their functional significance","volume":"38","author":"Dudley","year":"1990","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.bmc.2022.116804_b0135","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1440-1681.1997.tb01193.x","article-title":"Angiotensin II receptors and renin in the porcine uterus: myometrial AT2 and endometrial AT1 receptors are down-regulated during gestation","volume":"24","author":"Nielsen","year":"1997","journal-title":"Clinic Experi Pharmacol Physiol."},{"key":"10.1016\/j.bmc.2022.116804_b0140","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1021\/jm00112a031","article-title":"Nonpeptide angiotensin II receptor antagonists: the discovery of a series of N-(biphenylylmethyl)imidazoles as potent, orally active antihypertensives","volume":"34","author":"Carini","year":"1991","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0145","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1021\/jm9504722","article-title":"Nonpeptide Angiotensin II Receptor Antagonists: The Next Generation in Antihypertensive Therapy","volume":"39","author":"Wexler","year":"1996","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0150","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/0006-2952(94)90520-7","article-title":"Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance","volume":"47","author":"Houston","year":"1994","journal-title":"Biochem Pharmacol."},{"issue":"1350\u20131359","key":"10.1016\/j.bmc.2022.116804_b0155","article-title":"Prediction of Human Clearance of Twenty-Nine Drugs from Hepatic Microsomal Intrinsic Clearance Data: An Examination of In Vitro Half-Life Approach and Nonspecific Binding to Microsomes","volume":"27","author":"Obach","year":"1999","journal-title":"Drug Metab Dispos."},{"key":"10.1016\/j.bmc.2022.116804_b0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2020.115859","article-title":"N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands","volume":"29","author":"Wannberg","year":"2021","journal-title":"Bioorg Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0165","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10593-015-1671-z","article-title":"Preparation of 2-(1-adamantyl)-1H-benzimidazole and novel derivatives thereof","volume":"51","author":"Zurabishvili","year":"2015","journal-title":"Chem Heterocycl Compd."},{"key":"10.1016\/j.bmc.2022.116804_b0170","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1016\/j.bmc.2012.06.011","article-title":"Synthesis and biological evaluation of 4\u2032-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II\/endothelin A receptor antagonists","volume":"20","author":"Bai","year":"2012","journal-title":"Bioorg Med Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0175","doi-asserted-by":"crossref","first-page":"5811","DOI":"10.1039\/C7OB00945C","article-title":"One-pot strategy of copper-catalyzed synthesis of 1,2-disubstituted benzimidazoles","volume":"15","author":"Xie","year":"2017","journal-title":"Org Biomol Chem."},{"key":"10.1016\/j.bmc.2022.116804_b0180","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1021\/op300003b","article-title":"Evaluation of a Novel Non-Resonant Microwave Reactor for Continuous-Flow Chemistry","volume":"16","author":"\u00d6hrngren","year":"2012","journal-title":"Org Proc Res Dev."}],"container-title":["Bioorganic &amp; Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089622001961?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089622001961?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T01:18:15Z","timestamp":1760836695000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089622001961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7]]},"references-count":36,"alternative-id":["S0968089622001961"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2022.116804","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2022,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"2-Alkyl substituted benzimidazoles as a new class of selective AT2 receptor ligands","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2022.116804","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"116804"}}