{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:18:45Z","timestamp":1790774325464,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>First\u2010generation soluble guanylate cyclase (sGC) stimulators have shown clinical benefit in pulmonary hypertension (riociguat) and chronic heart failure (vericiguat). However, given the broad therapeutic opportunities for sGC stimulators, tailored molecules for distinct indications are required.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We report the high\u2010throughput screening (HTS)\u2010based discovery of a second generation of sGC stimulators from a novel imidazo[1,2\u2010<jats:italic>a<\/jats:italic>]pyridine lead series. An intense medicinal chemistry programme resulted in the discovery of the sGC stimulator BAY 1165747 (BAY\u2010747). The pharmacokinetic profile of BAY\u2010747 was determined in different species, and it was broadly characterized in pharmacological model systems relevant for vasodilatation and hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>BAY\u2010747 is a highly potent sGC stimulator in vitro. In addition, BAY\u2010747 showed an excellent pharmacokinetic profile with long half\u2010life and low peak\u2010to\u2010trough ratio. BAY\u2010747 was investigated in experimental <jats:italic>in vivo<\/jats:italic> models of malignant and resistant hypertension (rHT). In spontaneously hypertensive (SH) rats, BAY\u2010747 caused a dose\u2010related and long\u2010lasting decrease in mean arterial blood pressure (MAP). Oral treatment over 12\u2009days resulted in a persistent decrease. BAY\u2010747 provided additional benefit when dosed on top of losartan, amlodipine or spironolactone and even on top of triple combinations of frequently used antihypertensive drugs. In a new canine model of rHT, BAY\u2010747 caused a dose\u2010related and long\u2010lasting (&gt;6\u2009h) MAP decrease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>BAY\u2010747 is a potent, orally available sGC stimulator. BAY\u2010747 shows long\u2010acting pharmacodynamic effects with a very low peak\u2010to\u2010trough ratio. BAY\u2010747 could be a treatment alternative for patients with hypertension, especially those not responding to standard\u2010of\u2010care therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16142","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T08:10:59Z","timestamp":1683879059000},"page":"2500-2513","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification and characterization of the new generation soluble guanylate cyclase stimulator BAY\u2010747 designed for the treatment of resistant hypertension"],"prefix":"10.1111","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1311-2357","authenticated-orcid":false,"given":"Frank","family":"Wunder","sequence":"first","affiliation":[{"name":"Lead Identification &amp; Characterization, Pharma Research and Development Center Bayer AG  Wuppertal 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