{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T08:37:41Z","timestamp":1792831061468,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012309","name":"Royal Golden Jubilee (RGJ) Ph.D. Programme","doi-asserted-by":"publisher","award":["PHD\/0228\/2561"],"award-info":[{"award-number":["PHD\/0228\/2561"]}],"id":[{"id":"10.13039\/501100012309","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2026,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n We synthesised a series of\n N<\/jats:italic>\n 2<\/jats:sup>\n ,\n N<\/jats:italic>\n 4<\/jats:sup>\n \u2010diaminoquinazoline derivatives, among which 3\u2010[[4\u2010(benzylamino)quinazolin\u20102\u2010yl]amino]benzenesulfonamide (compound\n 5<\/jats:bold>\n ) exhibited potent phosphodiesterase type 5 (PDE5) inhibitory activity. Increasing evidence suggests that PDE5 inhibition is a promising therapeutic strategy for peripheral vascular disease. This study aimed to investigate vasorelaxant effects of\n 5<\/jats:bold>\n and its underlying mechanisms in rat mesenteric arteries. Compound\n 5<\/jats:bold>\n was synthesised and purified, and evaluated its vascular activity using organ bath assay. Molecular docking was performed to identify its potential molecular targets. Compound\n 5<\/jats:bold>\n (0.0001\u201330\u2009\u03bcM) induced relaxation of phenylephrine (PE)\u2010precontracted mesenteric arteries (EC\n 50<\/jats:sub>\n \u2009=\u20090.76\u2009\u00b1\u20090.29\u2009\u03bcM;\n E<\/jats:italic>\n max<\/jats:sub>\n \u2009=\u200995.6%\u2009\u00b1\u20091.1%). This effect was attenuated by endothelium removal (EC\n 50<\/jats:sub>\n \u2009=\u20095.24\u2009\u00b1\u20090.98\u2009\u03bcM) and by L\u2010NAME (eNOS inhibitor). Compound\n 5<\/jats:bold>\n enhanced sodium nitroprusside\u2013induced relaxation, supporting modulation of the NO\u2013sGC\u2013cGMP axis via PDE5 inhibition. Iberiotoxin (BK\n Ca<\/jats:sub>\n blocker) reduced relaxation, whereas 4\u2010aminopyridine (K\n V<\/jats:sub>\n blocker) and glibenclamide (K\n ATP<\/jats:sub>\n blocker) had no effect. Compound\n 5<\/jats:bold>\n inhibited vasoconstriction mediated by extracellular Ca\n 2+<\/jats:sup>\n influx via receptor\u2010operated Ca\n 2+<\/jats:sup>\n channels (ROCCs) and \u03b1\n 1<\/jats:sub>\n \u2010adrenergic receptor activation. Molecular docking provided qualitative support for PDE5A, BK\n Ca<\/jats:sub>\n channels and \u03b1\n 1<\/jats:sub>\n \u2010adrenergic receptor as potential targets. In conclusion,\n 5<\/jats:bold>\n induces potent vasorelaxation in resistance arteries through eNOS\/NO\/cGMP signalling, BK\n Ca<\/jats:sub>\n channel activation and inhibition of ROCCs and \u03b1\n 1<\/jats:sub>\n \u2010adrenergic receptors, supporting its potential as a therapeutic candidate for peripheral vascular disorders.\n <\/jats:p>","DOI":"10.1111\/bcpt.70324","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T08:11:16Z","timestamp":1792829476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["3\u2010[[4\u2010(Benzylamino)quinazolin\u20102\u2010yl] Amino] Benzenesulfonamide, a Quinazoline\u2010Based PDE5 Inhibitor, Induces Vasorelaxation in Rat Mesenteric Arteries via Multiple Mechanisms"],"prefix":"10.1111","volume":"139","author":[{"given":"Usana","family":"Chatturong","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry Naresuan University Phitsanulok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6973-158X","authenticated-orcid":false,"given":"Krongkarn","family":"Chootip","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry Naresuan University Phitsanulok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6998-7446","authenticated-orcid":false,"given":"M. Paul","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering King Mongkut's Institute of Technology, Ladkrabang Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5072-1397","authenticated-orcid":false,"given":"Guntur","family":"Guntur","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering King Mongkut's Institute of Technology, Ladkrabang Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-6007","authenticated-orcid":false,"given":"Yasuteru","family":"Shigeta","sequence":"additional","affiliation":[{"name":"Center for Computational Sciences University of Tsukuba Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-3844","authenticated-orcid":false,"given":"Kowit","family":"Hengphasatporn","sequence":"additional","affiliation":[{"name":"Center for Computational Sciences University of Tsukuba Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perle","family":"Totoson","sequence":"additional","affiliation":[{"name":"Marie and Louis Pasteur University, EFS, INSERM, RIGHT (UMR1098) Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Demougeot","sequence":"additional","affiliation":[{"name":"Marie and Louis Pasteur University, EFS, INSERM, RIGHT (UMR1098) Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.111128","article-title":"Phosphodiesterase 5 (PDE5): Structure\u2010Function Regulation and Therapeutic Applications of Inhibitors","volume":"134","author":"Ahmed W. 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