5-Alkylidene-3,5-dihydro-4H-imidazol-4-one derivatives were synthesized and evaluated for activity as angiotensin II receptor antagonists. Substitutions at C-2 and C-5, respectively, with a propyl group and a 1-methylethylidene group resulted in the optimal compound, 3,5-dihydro-5-(1-methylethylidene)-2-propyl-3-[[2'-(1H-tetrazol - 5-yl)biphenyl-4-yl]methyl]-4H-imidazol-4-one (2b), with a pA2 value of 8.85 in rabbit aorta. When administered orally to rats, 2b showed a greater inhibitory effect on angiotensin II-induced pressor response than DuP 753. Compound 2b also showed a good antihypertensive effect when administered orally to conscious sodium-depleted spontaneously hypertensive rats, with a duration of action of 24 h. These data suggest that 2b may be a useful agent for the treatment of angiotensin II-dependent diseases such as hypertension.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1248/cpb.46.777 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
RNA-Seq transcriptomic landscape profiling of spontaneously hypertensive rats in youth treated with a ARNI versus ARB.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Chongqing, 400010, China.
Angiotensin receptor-neprilysin inhibitor (ARNI) and angiotensin II receptor blockers (ARB) are antihypertension medications that improve cardiac remodeling and protect the heart. However, at the early stage of hypertension, it is still unclear how these two drugs affect the transcriptomic profile of multiple organs in hypertensive rats and the transcriptomic differences between them. We performed RNA sequencing to define the RNA expressing profiles of the eight tissues (atrium, ventricle, aorta, kidney, brain, lung, white fat, and brown fat) in spontaneously hypertensive rats (SHRs) and SHRs treated with ARNI or ARB.
View Article and Find Full Text PDFThe Early Pharmacological Strategy with Inodilator, bEta-blockers, Mineralocorticoid Receptor Antagonists, Sodium-glucose coTransporter-2 Inhibitors and Angiotensin Receptor-neprylisin Inhibitors in Acute Heart Failure (PENTA-HF).
Curr Vasc Pharmacol
January 2025
IRCCS San Raffaele Cassino, 03043, Cassino, Italy.
Purpose: The management of acute heart failure (AHF) is crucial and challenging. Regarding the use of inotropes, correct patient selection and time of administration are of the essence. We hypothesize that the early use of Levosimendan favouring hemodynamic stabilization and enables rapid optimization of guideline-directed medical treatment (GDMT) in patients with HF, eventually impacting the patient's prognosis during the vulnerable phase.
View Article and Find Full Text PDFBroad-spectrum affinity chromatography of SARS-CoV-2 and Omicron vaccines from ligand screening to purification.
J Chromatogr A
January 2025
Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address:
Emerging variants of SARS-CoV-2 pose great technological and regulatory challenges to vaccine manufacturing, especially in downstream processing. To address this dilemma, the development of broad-spectrum affinity chromatography for the purification of wild-type SARS-CoV-2 and its variants is crucial. We propose a comprehensive strategy to achieve this goal via the identification of high-affinity peptides by affinity selection of phage display and next-generation sequencing (NGS) and the evaluation of chromatographic performance.
View Article and Find Full Text PDFTWEAK/Fn14 axis may promote vascular smooth muscle cell senescence via p38 signaling pathway: preliminary evidence.
Future Sci OA
December 2025
Department of Gerontology, the First Affiliated Hospital, China Medical University, Shenyang, China.
Aim: The primary objective of this study is to investigate the impact of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), on the process of vascular smooth muscle cell (VSMC) senescence.
Methods: Rat arterial VSMCs were cultured with angiotensin II to establish a model of premature senescence. The effects of TWEAK and Fn14 on senescent VSMCs were evaluated.
Gut Microbiota Metabolites Sensed by Host GPR41/43 Protect Against Hypertension.
Circ Res
January 2025
Hypertension Research Laboratory, School of Biological Sciences (R.R.M., T.Z., E.D., L.X., A.B.-W., H.A.J., M.N., M.P., K.C.L., W.Q., J.A.O.D., F.Z.M.).
Background: Fermentation of dietary fiber by the gut microbiota leads to the production of metabolites called short-chain fatty acids, which lower blood pressure and exert cardioprotective effects. Short-chain fatty acids activate host signaling responses via the functionally redundant receptors GPR41 and GPR43, which are highly expressed by immune cells. Whether and how these receptors protect against hypertension or mediate the cardioprotective effects of dietary fiber remains unknown.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!