Tag: M.W=400-450

Ohishi, Mitsuru published the artcileSacubitril/valsartan-A new weapon for fighting the hypertension paradox, HPLC of Formula: 137862-53-4, the publication is Hypertension Research (2022), 45(5), 915-916, database is CAplus and MEDLINE.

The estimated prevalence of hypertension in Japan is 43 million. However, when good blood pressure (BP) control is defined as <140/90 mmHg, only 12 million patients have achieved the targeted BP. Thus, 27% of individuals with hypertension have achieved satisfactory BP control. The guidelines for the management of hypertension by the Japanese Society of Hypertension (JSH2019) recommended that the antihypertensive target should be <130/80 mmHg, except in older individuals (≥75 years); individuals with cerebrovascular disease, with bilateral carotid artery stenosis or occlusion of the main cerebral artery; or individuals with chronic kidney disease without proteinuria. In the excluded groups, excessive antihypertensive treatments may increase adverse drug effects. Studies have shown that 21.6% of all patients with hypertension have achieved a BP <130/80 mmHg, and the control rate is lower among younger individuals. Sacubitril/valsartan is a new type of antihypertensive drug combination that contains a 1:1 molar ratio of the angiotensin receptor blocker valsartan and the neprilysin inhibitor sacubitril. A recent phase III study assessed the efficacy and safety of sacubitril/valsartan vs. olmesartan in Japanese patients with mild-to-moderate essential hypertension. Strict BP control without giving up will make it possible to extend our healthy life expectancy by preventing stroke and cardiovascular diseases.

Hypertension Research published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, HPLC of Formula: 137862-53-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Gilstrap, Lauren published the artcileSacubitril/valsartan vs ACEi/ARB at hospital discharge and 5-year survival in older patients with heart failure with reduced ejection fraction: A decision analysis approach, Product Details of C24H29N5O3, the publication is American Heart Journal (2022), 23-28, database is CAplus and MEDLINE.

In clin. trials, sacubitril/valsartan has demonstrated significant survival benefits compared to angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Whether older patients with heart failure with reduced ejection fraction (HFrEF) benefit as much, due to higher rates of comorbidities, frailty and drug discontinuation, is unknown. Using a cohort of Medicare beneficiaries hospitalized with HFrEF between 2016 and 2018, we determined all-cause mortality and HF-readmission rates among patients not given ACEi/ARB or sacubitril/valsartan at hospital discharge, by age. We then used risk reductions from the SOLVD, PARADIGM-HF and PIONEER-HF trials to estimate the benefits of ACEi/ARB and sacubitril/valsartan. We then incorporated age-specific estimates of drug discontinuation from Medicare. A Markov decision process model was used to simulate 5-yr survival and estimate number needed to treat, comparing discharge on ACEi/ARB vs sacubitril/valsartan by age. After accounting for drug discontinuation rates, which were surprisingly slightly higher among those discharged on ACEi/ARB (2.3%/mo vs 1.9%/mo), there was a small but significant survival advantage to discharge on sacubitril/valsartan over 5 years (+0.81 mo [95% CI 0.80, 0.81]). The benefit of sacubitril/valsartan over ACEi/ARB did not decrease with increasing age – the number needed to treat among 66 to 74-yr-old patients was 84 and among 85+ year-old patients was 67. Even after accounting for “real world” rates of drug discontinuation, discharge on sacubitril/valsartan after conferred a small, but significant, survival advantage which does not appear to wane with increasing age.

American Heart Journal published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Product Details of C24H29N5O3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Li, Miaomiao published the artcileUse of levosimendan combined with Shenfu injection to treat acute heart failure patients with hypotension: a prospective randomized controlled single-blind study, Recommanded Product: (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is BMC Cardiovascular Disorders (2022), 22(1), 130, database is CAplus and MEDLINE.

Levosimendan can improve clin. symptoms and the cardiorenal rescue success rate, and stabilize hemodynamic parameters in individuals suffering from acute decompensated heart failure. In addition, Shenfu injection (SFI) has been shown to protect the ischemic heart and enhance myocardial contractility. For this randomized control single-blind study, 101 patients with acute decompensated heart failure (ADHF) were enrolled and randomly assigned to control levosimendan (n = 51) and levosimendan + SFI injection (n = 50) groups. Attending physicians were not blinded for which arm the patients were allocated. Blood pressure, heart rate, the ECG, respiratory rate, fluid intake and urine output were all recorded 2 h and 24 h after drug infusions had commenced, and the cardiac index (CI) was monitored by ultrasonic cardiac output monitors. Median blood pressure was markedly increased in the levosimendan + SFI group after 2 h and 24 h from the initiation of infusions compared to levosimendan administration alone. Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P < 0.001). Alterations in BNP concentrations were not different in the combination and control groups. No differences were found between the 2 groups in heart rate or severe hypotension, but blood pressure (systolic blood pressure, diastolic blood pressure) and hemodynamic parameters including CI, cardiac output and stroke volume index responded better in the levosimendan + SFI group compared to the monotherapy levosimendan group. Levosimendan + SFI was superior to treat ADHF patients compared to levosimendan monotherapy and produced significant improvements in hemodynamic parameters especially for ADHF patients with hypotension.

BMC Cardiovascular Disorders published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Recommanded Product: (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Jia, Ruoyu published the artcileEffect of Sacubitril/Valsartan on renal function in patients with chronic kidney disease and heart failure with preserved ejection fraction: A real-world 12-week study, Application In Synthesis of 137862-53-4, the publication is European Journal of Pharmacology (2022), 175053, database is CAplus and MEDLINE.

Patients with chronic kidney disease (CKD) are often complicated with heart failure with preserved ejection fraction (HFpEF). However, several drugs, including angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB), have not shown apparent benefits in terms of morbidity and mortality of HFpEF. PARAMOUNT and other studies have shown the potential benefits of Sacubitril/Valsartan on patients with HFpEF, but its effects on renal function and the effect of low-dose Sacubitril/Valsartan in actual clin. conditions have not been thoroughly evaluated. In our longitudinal and observational research, 353 patients were followed up for 12 wk. We evaluated renal function [urinary protein, serum creatinine and estimated glomerular filtration rate (eGFR)] and cardiac function [NT-proBNP (brain natriuretic peptide), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), left atrial width and left ventricular end-diastolic width] at baseline and during follow-up. Worsening renal function (WRF) was defined as an increased serum creatinine≥26.5umol/L or decreased eGFR≥20%. The decline of eGFR in the Sacubitril/Valsartan group was slower than that in the control group (p = 0.021). The outcome of proteinuria in the ACEI/ARB group was significantly better than that in the Sacubitril/Valsartan group (p = 0.001). In terms of echocardiogram, the average left atrial width in Sacubitril/Valsartan group decreased by 1.38 ± 3.02 mm, which was significantly lower than that in the ACEI/ARB group (p = 0.02). The increase of urine protein class in the ACEI/ARB group increased the risk of WRF with statistical significance (OR = 2.36, 95%CI 1.01-5.49, p = 0.047), but no statistical significance was found in all the patients or Sacubitril/Valsartan group. In conclusion, Sacubitril/Valsartan could more effectively slow down renal function decline and reverse myocardial remodeling in patients with CKD and HFpEF than ACEI/ARB, even at low doses, though its protective effect on urinary protein is not as good as that of ACEI/ARB.

European Journal of Pharmacology published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Application In Synthesis of 137862-53-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Mochizuki, Tatsuki published the artcileEffect of Cyclosporin A and Impact of Dose Staggering on OATP1B1/1B3 Endogenous Substrates and Drug Probes for Assessing Clinical Drug Interactions, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is Clinical Pharmacology & Therapeutics (Hoboken, NJ, United States) (2022), 111(6), 1315-1323, database is CAplus and MEDLINE.

This study was designed to assess the quant. performance of endogenous biomarkers for organic anion transporting polypeptide (OATP) 1B1/1B3-mediated drug-drug interactions (DDIs). Ten healthy volunteers orally received OATP1B1/1B3 probe cocktail (0.2 mg pitavastatin, 1 mg rosuvastatin, and 2 mg valsartan) and an oral dose of cyclosporin A (CysA, 20 mg and 75 mg) separated by a 1-h interval (20 mg (-1 h), and 75 mg (-1 h)). CysA 75 mg was also given with a 3-h interval (75 mg (-3 h)) to examine the persistence of OATP1B1/1B3 inhibition. The area under the plasma concentration-time curve ratios (AUCRs) were 1.63, 3.46, and 2.38 (pitavastatin), 1.39, 2.16, and 1.81 (rosuvastatin), and 1.42, 1.77, and 1.85 (valsartan), at 20 mg, 75 mg (-1 h) and 75 mg (-3 h) of CysA, resp. CysA effect on OATP1B1/1B3 was unlikely to persist at the dose examined Among 26 putative OATP1B1/1B3 biomarkers evaluated, AUCR and maximum concentration ratio (C_maxR) of CP-I showed the highest Pearson′s correlation coefficient with CysA AUC (0.94 and 0.93, resp.). Correlation between AUCR of pitavastatin, and C_maxR or AUCR of CP-I were consistent between this study and our previous study using rifampicin as an OATP1B1/1B3 inhibitor. Nonlinear regression anal. of AUCR^-1 of pitavastatin and CP-I against CysA C_max yielded K_{i,OATP1B1/1B3,app} (109 ± 35 and 176 ± 42 nM, resp.), similar to the K_{i,OATP1B1/1B3} estimated by our physiol.-based pharmacokinetic model anal. described previously (107 nM). The endogenous OATP1B1/1B3 biomarkers, particularly C_maxR and AUCR of CP-I, corroborates OATP1B1/1B3 inhibition and yields valuable information that improve accurate DDI predictions in drug development, and enhance our understanding of interindividual variability in the magnitude of DDIs.

Clinical Pharmacology & Therapeutics (Hoboken, NJ, United States) published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Zhang, Yue published the artcileAngiotensin receptor-neprilysin inhibitor attenuates cardiac hypertrophy and improves diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction, Synthetic Route of 137862-53-4, the publication is Clinical and Experimental Pharmacology and Physiology (2022), 49(8), 848-857, database is CAplus and MEDLINE.

LCZ696, an angiotensin receptor-neprilysin inhibitor, has shown promising clin. efficacy in patients with heart failure (HF) with reduced ejection fraction. However, its potential effects on heart failure with preserved ejection fraction (HFpEF) are still not fully understood. We evaluated the effect of LCZ696 on HFpEF in transverse aortic constriction mice and compared it with the effect of the angiotensin receptor blocker, valsartan. We found that LCZ696 improved cardiac diastolic function by reducing ventricular hypertrophy and fibrosis in mice with overload-induced diastolic dysfunction. In addition, there was superior inhibition of LCZ696 than stand-alone valsartan. As a potential underlying mechanism, we demonstrated that LCZ696 behaves as a potent suppressor of calcium-mediated calcineurin-nuclear factor of activated T cells (NFAT) signalling transduction pathways. Hence, we demonstrated the protective effects of LCZ696 in overload-induced HFpEF and provided a pharmaceutical therapeutic strategy for related diseases.

Clinical and Experimental Pharmacology and Physiology published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C17H19N3O7S, Synthetic Route of 137862-53-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Liu, Shanshan published the artcileProtective effect of sacubitril/valsartan in patients with acute myocardial infarction: a meta-analysis, HPLC of Formula: 137862-53-4, the publication is Experimental and Therapeutic Medicine (2022), 23(6), 406, database is CAplus and MEDLINE.

Meta-anal. of the effects and safety of sacubitril/valsartan in patients with acute myocardial infarction (AMI), a total of four databases, including PubMed, Cochrane Library, Embase and Web of Science, and the ClinicalTrials.gov website were searched. Using a combination of medical subject headings and entry terms, the final search was performed in July 2021. A manual search of cross-references from the original articles was also conducted. The meta-anal. was subsequently performed with Revman 5.3 software and a total of four studies comprising 586 patients were included. The results disclosed a significant reduction in major adverse cardiovascular and cerebrovascular events (MACCEs) [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.30-0.73; P = 0.0007], readmission (OR, 0.45; 95% CI, 0.29-0.71; P = 0.0006), incidence of acute heart failure (AHF) (OR, 0.45; 95% CI, 0.28-0.71; P = 0.0007) and N-terminal pro B-type natriuretic peptide [standardized mean difference (SMD), -0.88; 95% CI, -1.55-(-0.21); P = 0.01] in the sacubitril/valsartan group compared with that in the control group, and a random effects model was used to pool these data. No significant differences were identified in the incidence of hypotension (OR, 2.91; 95% CI, 0.55-15.51; P = 0.21), adverse events (OR, 2.19; 95% CI, 0.42-11.37; P = 0.35), left ventricular ejection fraction (mean difference, 1.96; 95% CI, -0.84-4.76; P = 0.17) or soluble suppression of tumorigenesis-2 (SMD, -0.45; 95% CI, -1.62-0.71; P = 0.45) according to the random effects model. In conclusion, the present meta-anal. revealed that sacubitril/valsartan was able to effectively reduce the incidence of MACCEs, readmission and AHF in patients with AMI after revascularization without any obvious adverse events.

Experimental and Therapeutic Medicine published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, HPLC of Formula: 137862-53-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Na, Joo Young published the artcileComparative Pharmacokinetics Between a Fixed-Dose Combination of Pitavastatin/Valsartan 4/160 mg and the Corresponding Individual Components Through a Partial Replicated Crossover Design in Healthy Male Subjects, SDS of cas: 137862-53-4, the publication is Clinical Pharmacology in Drug Development (2022), 11(5), 615-622, database is CAplus and MEDLINE.

Hypertension and hyperlipidemia are often comorbid, requiring combination therapies of antihypertensive drugs and antihyperlipidemia drugs. Taking 1 fixed-dose combination (FDC) may increase patient compliance rather than taking each of the drugs sep. This study aimed to evaluate the pharmacokinetic bioequivalence between an FDC of pitavastatin/valsartan 4/160 mg and the corresponding individual components. Considering that valsartan is a highly variable drug for maximum plasma concentration (C_max), an open-label, randomized, partial replicated crossover study was conducted in 54 healthy subjects. The subjects received a single oral dose of the FDC of pitavastatin/valsartan 4/160 mg in 1 period or the corresponding individual components in the other 2 periods. The geometric mean ratios and their 90%CIs of the FDC to the corresponding individual components for C_max and area under the concentration-time curve from time 0 to the last measurable time point were 1.05 (90%CI, 0.96-1.15) and 0.10 (90%CI, 0.95-1.04) for pitavastatin and 1.15 (90%CI, 1.06-1.25) and 1.06 (0.99-1.14) for valsartan, resp. The geometric mean ratios (90%CIs) for area under the concentration-time curve from time 0 to the last measurable time point and C_max of both drugs were included in the bioequivalence criteria. In conclusion, the FDC of pitavastatin/valsartan 4/160 mg showed pharmacokinetic equivalence with the corresponding individual components.

Clinical Pharmacology in Drug Development published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, SDS of cas: 137862-53-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Lai, Ping published the artcileEmerging trends in sacubitril/valsartan research: A bibliometric analysis of the years 1995-2021., Quality Control of 137862-53-4, the publication is Medicine (2022), 101(31), e29398, database is MEDLINE.

BACKGROUND: Sacubitril/valsartan has been approved for the treatment of heart failure (HF) patients with reduced ejection fraction; since then, it gradually became a new star drug in the therapy of HF. Nevertheless, the effectiveness of sacubitril/valsartan remains under investigation. Thus far, only a few bibliometric studies have systematically analyzed the application of sacubitril/valsartan. METHODS: Publications on sacubitril/valsartan were retrieved from the Web of Science Core Collection on April 29, 2021. Data were analyzed using Microsoft Excel 2019 (Redmond, WA), VOS viewer (Redmond, WA), and Cite Space V (Drexel University, Philadelphia, PA). RESULTS: A total of 1309 publications on sacubitril/valsartan published from 1995 to 2021 were retrieved. The number of publications regarding sacubitril/valsartan increased sharply in the last 6 years (2015-2021), and American scholars authored >40% of those publications. Most were published in the European Journal of Heart Failure, the United States was the bellwether with a solid academic reputation in this area. Solomon published the highest number of related articles and was the most frequently cited author. “Heart failure” was the leading research hotspot. The keywords, “inflammation,” “fibrosis,” and “oxidative stress” appeared most recently as research fronts. CONCLUSIONS: Research attention should be focused on clinical trial outcomes. Considering its effectiveness in HF, the mechanisms and further applications of sacubitril/valsartan may become research hotspots in the future and should be closely examined.

Medicine published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Quality Control of 137862-53-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Peng, L Q published the artcileEffects of Wenyang Zhenshuai Granules on the Expression of Key Mitochondrial Autophagy Proteins in the Doxorubicin-Induced Model of H9c2 Cardiomyocyte Injury., Quality Control of 137862-53-4, the publication is Bulletin of experimental biology and medicine (2022), 173(3), 335-340, database is MEDLINE.

This study aimed to explore the effects of Wenyang Zhenshuai granules (WZG) on the morphology of cardiomyocytes, cell viability, and the expression of key mitochondrial autophagy proteins in the doxorubicin-induced model of H9c2 cardiomyocyte injury. Cardiomyocytes were cultured for 44 h and divided into 4 groups: intact control, doxorubicin-injured cells (DOX), doxorubicin-injured cells treated with WZG (DOX+WZG), and doxorubicin-injured cells treated with valsartan (DOX+valsartan; reference group). The morphology of cardiomyocytes was analyzed under an inverted microscope; cardiomyocyte survival rate was determined by MTT assay. The expression of the key mitochondrial autophagy proteins (PINK1, parkin, LC3-II, and prohibitin-2) was analyzed by Western blotting. WZG down-regulated the expression of the key mitochondrial autophagy proteins in DOX-injured cells, which may be one of the important mechanisms for regulating ventricular remodeling and cardiomyocyte apoptosis.

Bulletin of experimental biology and medicine published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Quality Control of 137862-53-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics