{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:14:08Z","timestamp":1791004448007,"version":"4.1.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2020-777"],"award-info":[{"award-number":["075-15-2020-777"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The Na\n                    <jats:sup>+<\/jats:sup>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. Herein we report novel NHE-1 inhibitors realized via functionalization of\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>1<\/jats:sup>\n                    -alkyl quinazoline-2,4(1\n                    <jats:italic>H<\/jats:italic>\n                    ,3\n                    <jats:italic>H<\/jats:italic>\n                    )-dione and quinazoline-4(3\n                    <jats:italic>H<\/jats:italic>\n                    )-one with\n                    <jats:italic>N<\/jats:italic>\n                    -acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in a nanomolar range. Their pharmacophoric features were elucidated with neural network modeling. Several compounds combine NHE-1 inhibition with antiplatelet activity. Compound\n                    <jats:bold>6b<\/jats:bold>\n                    reduces intraocular pressure in rats and effectively inhibits the formation of glycated proteins. Compounds\n                    <jats:bold>3e<\/jats:bold>\n                    and\n                    <jats:bold>3i<\/jats:bold>\n                    inhibit pro-inflammatory activation of murine macrophages, LPS-induced interleukin-6 secretion and also exhibit antidepressant activity similar to amiloride. Hence, novel compounds represent an interesting starting point for the development of agents against cardiovascular diseases, thrombotic events, excessive inflammation, long-term diabetic complications and glaucoma.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-03722-w","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T06:03:53Z","timestamp":1640066633000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis and multifaceted pharmacological activity of novel quinazoline NHE-1 inhibitors"],"prefix":"10.1038","volume":"11","author":[{"given":"Alexander","family":"Spasov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ozerov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Vassiliev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Kosolapov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Gurova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Kucheryavenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Naumenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Babkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Sirotenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Taran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Litvinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Borisov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladlen","family":"Klochkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Merezhkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Miroshnikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgy","family":"Uskov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezhda","family":"Ovsyankina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"3722_CR1","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1152\/physrev.00028.2018","volume":"99","author":"SF Pedersen","year":"2019","unstructured":"Pedersen, S. F. & Counillon, L. The SLC9A-C mammalian Na+\/H+ exchanger family: molecules, mechanisms, and physiology. Physiol. Rev. 99, 2015\u20132113 (2019).","journal-title":"Physiol. Rev."},{"key":"3722_CR2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.yjmcc.2013.02.006","volume":"61","author":"M Karmazyn","year":"2013","unstructured":"Karmazyn, M. NHE-1: still a viable therapeutic target. J. Mol. Cell. Cardiol. 61, 77\u201382 (2013).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"3722_CR3","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/978-1-4614-4756-6_35","volume":"961","author":"Y Shi","year":"2013","unstructured":"Shi, Y., Kim, D., Caldwell, M. & Sun, D. The role of Na(+)\/h(+) exchanger isoform 1 in inflammatory responses: maintaining H(+) homeostasis of immune cells. Adv. Exp. Med. Biol. 961, 411\u2013418 (2013).","journal-title":"Adv. Exp. Med. Biol."},{"key":"3722_CR4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cellimm.2006.07.001","volume":"240","author":"P De Vito","year":"2006","unstructured":"De Vito, P. The sodium\/hydrogen exchanger: a possible mediator of immunity. Cell. Immunol. 240, 69\u201385 (2006).","journal-title":"Cell. Immunol."},{"key":"3722_CR5","doi-asserted-by":"crossref","first-page":"15210","DOI":"10.1523\/JNEUROSCI.3950-10.2010","volume":"30","author":"Y Liu","year":"2010","unstructured":"Liu, Y. et al. Activation of microglia depends on Na+\/H+ exchange-mediated H+ homeostasis. J. Neurosci. 30, 15210\u201315220 (2010).","journal-title":"J. Neurosci."},{"key":"3722_CR6","first-page":"1","volume":"2018","author":"Y Zhang","year":"2018","unstructured":"Zhang, Y. et al. Amelioration of Lipopolysaccharide-Induced Acute Lung Injury in Rats by Na-H Exchanger-1 Inhibitor Amiloride Is Associated with Reversal of ERK Mitogen-Activated Protein Kinase. BioMed Res. Int. 2018, 1\u20137 (2018).","journal-title":"BioMed Res. Int."},{"key":"3722_CR7","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.yebeh.2004.01.005","volume":"5","author":"A Ali","year":"2004","unstructured":"Ali, A., Ahmad, F. J., Pillai, K. K. & Vohora, D. Evidence of the antiepileptic potential of amiloride with neuropharmacological benefits in rodent models of epilepsy and behavior. Epilepsy. Behav. 5, 322\u2013328 (2004).","journal-title":"Epilepsy. Behav."},{"key":"3722_CR8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s11239-010-0530-0","volume":"31","author":"RJ Gumina","year":"2011","unstructured":"Gumina, R. J., Newman, P. J. & Gross, G. J. Effect on ex vivo platelet aggregation and in vivo cyclic flow with Na+\/H+ exchange inhibition: Gumina, NHE-1 inhibition and platelet aggregation. J. Thromb. Thrombolysis 31, 431\u2013435 (2011).","journal-title":"J. Thromb. Thrombolysis"},{"key":"3722_CR9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.phrs.2005.12.003","volume":"53","author":"K-S Lee","year":"2006","unstructured":"Lee, K.-S. et al. Anti-platelet activity of KR-32560, a novel sodium\/hydrogen exchanger-1 inhibitor. Pharmacol. Res. 53, 265\u2013270 (2006).","journal-title":"Pharmacol. Res."},{"key":"3722_CR10","first-page":"3","volume":"80","author":"AA Spasov","year":"2017","unstructured":"Spasov, A. A. et al. Effect of NHE-1 inhibitors zoniporide and RU-1355 on the hemorheological properties of blood under conditions of brain ischemia in rats. Eksp. Klin. Farmakol. 80, 3\u20137 (2017).","journal-title":"Eksp. Klin. Farmakol."},{"key":"3722_CR11","first-page":"1897","volume":"43","author":"MY Avila","year":"2002","unstructured":"Avila, M. Y., Seidler, R. W., Stone, R. A. & Civan, M. M. Inhibitors of NHE-1 Na+\/H+ exchange reduce mouse intraocular pressure. Invest. Ophthalmol. Vis. Sci. 43, 1897\u20131902 (2002).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"3722_CR12","first-page":"989","volume":"29","author":"S Lupachyk","year":"2012","unstructured":"Lupachyk, S. et al. Na +\/H +-exchanger-1 inhibition counteracts diabetic cataract formation and retinal oxidative-nitrative stress and apoptosis. Int. J. Mol. Med. 29, 989\u2013998 (2012).","journal-title":"Int. J. Mol. Med."},{"key":"3722_CR13","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1080\/02713683.2018.1458882","volume":"43","author":"A Dreffs","year":"2018","unstructured":"Dreffs, A., Henderson, D., Dmitriev, A. V., Antonetti, D. A. & Linsenmeier, R. A. Retinal pH and acid regulation during metabolic acidosis. Curr. Eye Res. 43, 902\u2013912 (2018).","journal-title":"Curr. Eye Res."},{"key":"3722_CR14","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.bbrc.2008.08.008","volume":"375","author":"S Wu","year":"2008","unstructured":"Wu, S. et al. Involvement of Na+\/H+ exchanger 1 in advanced glycation end products-induced proliferation of vascular smooth muscle cell. Biochem. Biophys. Res. Commun. 375, 384\u2013389 (2008).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"3722_CR15","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1517\/13543776.2013.788645","volume":"23","author":"F S\u0105czewski","year":"2013","unstructured":"S\u0105czewski, F. & Balewski, \u0141. Biological activities of guanidine compounds, 2008\u20132012 update. Expert Opin. Ther. Pat. 23, 965\u2013995 (2013).","journal-title":"Expert Opin. Ther. Pat."},{"key":"3722_CR16","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1016\/j.ejmech.2011.06.011","volume":"46","author":"L Jin","year":"2011","unstructured":"Jin, L. et al. Synthesis and Na+\/H+ exchanger inhibitory activity of benzoylguanidine derivatives. Eur. J. Med. Chem. 46, 4107\u20134116 (2011).","journal-title":"Eur. J. Med. Chem."},{"key":"3722_CR17","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1021\/op300331b","volume":"17","author":"W Tang","year":"2013","unstructured":"Tang, W. et al. Synthesis of a sodium-hydrogen exchange type 1 Inhibitor: an efficient Cu-catalyzed conjugated addition of a grignard reagent to an acetyl pyridinium salt. Org. Process Res. Dev. 17, 382\u2013389 (2013).","journal-title":"Org. Process Res. Dev."},{"key":"3722_CR18","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1021\/jm0492305","volume":"48","author":"S Lee","year":"2005","unstructured":"Lee, S. et al. (5-Arylfuran-2-ylcarbonyl)guanidines as cardioprotectives through the Inhibition of Na+\/H+ exchanger isoform-1. J. Med. Chem. 48, 2882\u20132891 (2005).","journal-title":"J. Med. Chem."},{"key":"3722_CR19","doi-asserted-by":"crossref","first-page":"3474","DOI":"10.1038\/s41467-021-23496-z","volume":"12","author":"Y Dong","year":"2021","unstructured":"Dong, Y. et al. Structure and mechanism of the human NHE1-CHP1 complex. Nat. Commun. 12, 3474 (2021).","journal-title":"Nat. Commun"},{"key":"3722_CR20","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/13543776.2018.1432596","volume":"28","author":"A Hameed","year":"2018","unstructured":"Hameed, A. et al. Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011\u20132016). Expert Opin. Ther. Pat. 28, 281\u2013297 (2018).","journal-title":"Expert Opin. Ther. Pat."},{"key":"3722_CR21","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/00397911.2018.1431282","volume":"48","author":"T Gupta","year":"2018","unstructured":"Gupta, T. et al. Current perspectives on quinazolines with potent biological activities: a review. Synth. Commun. 48, 1099\u20131127 (2018).","journal-title":"Synth. Commun."},{"key":"3722_CR22","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.2174\/1871520620666200627205321","volume":"21","author":"R Das","year":"2021","unstructured":"Das, R., Mehta, D. K. & Dhanawat, M. Bestowal of quinazoline Scaffold in anticancer drug discovery. Anticancer Agents Med. Chem. 21, 1350\u20131368 (2021).","journal-title":"Anticancer Agents Med. Chem."},{"key":"3722_CR23","first-page":"395637","volume":"2014","author":"M Asif","year":"2014","unstructured":"Asif, M. Chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives. Int. J. Med. Chem. 2014, 395637 (2014).","journal-title":"Int. J. Med. Chem."},{"key":"3722_CR24","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.3987\/COM-18-13904","volume":"96","author":"A Ozerov","year":"2018","unstructured":"Ozerov, A. et al. Pyrimidine derivatives of N-acetylguanidine: novel inhibitors of sodium-hydrogen exchanger 1. Heterocycles 96, 1101 (2018).","journal-title":"Heterocycles"},{"key":"3722_CR25","unstructured":"Petrov, V. I. et al. Derivatives of quinazolin-4(3h)-one inhibiting sodium-hydrogen exchange. RU2654062C2 (2018)."},{"key":"3722_CR26","doi-asserted-by":"crossref","first-page":"571","DOI":"10.3109\/02713689109001766","volume":"10","author":"W Wang","year":"1991","unstructured":"Wang, W., Sasaki, H., Chien, D. S. & Lee, V. H. Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit: a comparison with corneal penetration. Curr. Eye Res. 10, 571\u2013579 (1991).","journal-title":"Curr. Eye Res."},{"key":"3722_CR27","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1007\/s11095-010-0132-8","volume":"27","author":"H Kidron","year":"2010","unstructured":"Kidron, H., Vellonen, K.-S., del Amo, E. M., Tissari, A. & Urtti, A. Prediction of the corneal permeability of drug-like compounds. Pharm. Res. 27, 1398\u20131407 (2010).","journal-title":"Pharm. Res."},{"key":"3722_CR28","doi-asserted-by":"crossref","first-page":"549","DOI":"10.2337\/db11-1120","volume":"61","author":"R Nagai","year":"2012","unstructured":"Nagai, R., Murray, D. B., Metz, T. O. & Baynes, J. W. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 61, 549\u2013559 (2012).","journal-title":"Diabetes"},{"key":"3722_CR29","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1080\/07328309308019003","volume":"12","author":"CC Hauh-Jyun","year":"1993","unstructured":"Hauh-Jyun, C. C. & Cerami, A. Mechanism of inhibition of advanced glycosylation by aminoguanidine in Vitro. J. Carbohydr. Chem. 12, 731\u2013742 (1993).","journal-title":"J. Carbohydr. Chem."},{"key":"3722_CR30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.19163\/1994-9480-2020-3(75)-159-165","volume":"75","author":"R Litvinov","year":"2020","unstructured":"Litvinov, R., Usmiyanova, L. E., Klimenko, D. R. & Gontareva, A. V. Paradoxal activity of aminoguanidine in the model of glycoxidation with copper cations. J. Volgogr. State Med. Univ. 75, 159\u2013165 (2020).","journal-title":"J. Volgogr. State Med. Univ."},{"key":"3722_CR31","unstructured":"Lal, B. et al. Tricyclic guanidine derivatives as sodium-proton exchange inhibitors. WO2006051476 (2006)."},{"key":"3722_CR32","first-page":"43","volume":"76","author":"AA Spasov","year":"2013","unstructured":"Spasov, A. A., Gurova, N. A. & Kharitonova, M. V. Structure and physiological role of NHE1 and pharmacological regulation of its activity. Eksp. Klin. Farmakol. 76, 43\u201348 (2013).","journal-title":"Eksp. Klin. Farmakol."},{"key":"3722_CR33","first-page":"17","volume":"76","author":"NA Gurova","year":"2013","unstructured":"Gurova, N. A., Spasov, A. A., Timofeeva, A. S., Zheltova, A. A. & Fedorchuk, V. I. Cardioprotective properties of zoniporide studied on experimental ischemia and reperfusion models in rat myocardium. Eksp. Klin. Farmakol. 76, 17\u201319 (2013).","journal-title":"Eksp. Klin. Farmakol."},{"key":"3722_CR34","first-page":"3","volume":"79","author":"AA Spasov","year":"2016","unstructured":"Spasov, A. A. et al. Neuroprotective properties of a new inhibitor of Na+\/H+ exchanger (compound RU-1355) on the model of focal ischemia in rats. Eksp. Klin. Farmakol. 79, 3\u20137 (2016).","journal-title":"Eksp. Klin. Farmakol."},{"key":"3722_CR35","first-page":"13","volume":"77","author":"AAA Spasov","year":"2014","unstructured":"Spasov, A. A., Gurova, N. A., Timofeeva, A. S. & Sorokin, S. M. Experimental study of the antiarrhythmic properties of zoniporide. Eksp. Klin. Farmakol. 77, 13\u201317 (2014).","journal-title":"Eksp. Klin. Farmakol."},{"key":"3722_CR36","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/cbdv.200800268","volume":"6","author":"D Mao","year":"2009","unstructured":"Mao, D. et al. Synthesis and Na(+)\/H(+) exchanger-1 inhibitory activity of substituted (quinolinecarbonyl)guanidine derivatives. Chem. Biodivers. 6, 1727\u20131736 (2009).","journal-title":"Chem. Biodivers."},{"key":"3722_CR37","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.bmcl.2009.01.060","volume":"19","author":"S Lee","year":"2009","unstructured":"Lee, S., Yi, K. Y., Youn, S. J., Lee, B. H. & Yoo, S. (2-Aryl-5-methylimidazol-4-ylcarbonyl)guanidines and (2-aryl-5-methyloxazol-4-ylcarbonyl)guanidines as NHE-1 inhibitors. Bioorg. Med. Chem. Lett. 19, 1329\u20131331 (2009).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"3722_CR38","doi-asserted-by":"crossref","first-page":"e3000411","DOI":"10.1371\/journal.pbio.3000411","volume":"18","author":"NP du Sert","year":"2020","unstructured":"du Sert, N. P. et al. Reporting animal research: explanation and elaboration for the ARRIVE guidelines 20. PLOS Biol. 18, e3000411 (2020).","journal-title":"PLOS Biol."},{"key":"3722_CR39","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1038\/sj.bjp.0704647","volume":"135","author":"K Kusumoto","year":"2002","unstructured":"Kusumoto, K. et al. In vitro and in vivo pharmacology of a structurally novel Na+-H+ exchange inhibitor, T-162559. Br. J. Pharmacol. 135, 1995\u20132003 (2002).","journal-title":"Br. J. Pharmacol."},{"key":"3722_CR40","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1023\/A:1008986329267","volume":"8","author":"D Rosskopf","year":"1999","unstructured":"Rosskopf, D. Sodium-hydrogen exchange and platelet function. J. Thromb. Thrombolysis 8, 15\u201324 (1999).","journal-title":"J. Thromb. Thrombolysis"},{"key":"3722_CR41","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/978-94-017-9257-8_12","volume":"17","author":"PM Vassiliev","year":"2014","unstructured":"Vassiliev, P. M. et al. Consensus Drug Design Using IT Microcosm. In Application of Computational Techniques in Pharmacy and Medicine 17, 369\u2013431 (2014).","journal-title":"Application of Computational Techniques in Pharmacy and Medicine"},{"key":"3722_CR42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1198\/000313007X172998","volume":"61","author":"JM Hilbe","year":"2007","unstructured":"Hilbe, J. M. Statistica 7. Am. Stat. 61, 91\u201394 (2007).","journal-title":"Am. Stat."},{"key":"3722_CR43","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s11094-009-0340-x","volume":"43","author":"VAA Anisimova","year":"2009","unstructured":"Anisimova, V. A. et al. Synthesis and pharmacological activity of 3-(2,2,2-trichloro-1- hydroxyethyl)imidazo [1, 2-a]benzimidazole dihydrochlorides. Pharm. Chem. J. 43, 491\u2013494 (2009).","journal-title":"Pharm. Chem. J."},{"key":"3722_CR44","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/01.ijg.0000212276.57853.19","volume":"15","author":"ME Pease","year":"2006","unstructured":"Pease, M. E., Hammond, J. C., Quigley, H. A. Manometric calibration and comparison of TonoLab and TonoPen tonometers in rats with experimental glaucoma and in normal mice. J. Glaucoma 15, 512\u2013519 (2006).","journal-title":"J. Glaucoma"},{"key":"3722_CR45","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.dib.2018.03.019","volume":"18","author":"AJ Marcus","year":"2018","unstructured":"Marcus, A. J. et al. Data on the effects of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds on intraocular pressure of ocular normotensive rats. Data Brief 18, 523\u2013554 (2018).","journal-title":"Data Brief"},{"key":"3722_CR46","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF00428203","volume":"85","author":"L Steru","year":"1985","unstructured":"Steru, L., Chermat, R., Thierry, B. & Simon, P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85, 367\u2013370 (1985).","journal-title":"Psychopharmacology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-03722-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-03722-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-03722-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T13:36:00Z","timestamp":1670074560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-03722-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,21]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["3722"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-03722-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-877643\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,21]]},"assertion":[{"value":"4 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24380"}}