Tag: M.W=400-450

Maciag, Monika published the artcilePharmacological assessment of zebrafish-based cardiotoxicity models, Category: amides-buliding-blocks, the publication is Biomedicine & Pharmacotherapy (2022), 112695, database is CAplus and MEDLINE.

Cardiotoxicity remains the most common reason for failure during drug development. Recently, the zebrafish (Danio rerio) model has emerged for the evaluation of drug-dependent cardiotoxicity and for the identification of cardioprotective mols. However, it remains unknown how closely the zebrafish-based results may be translated to humans. To tackle this issue, we established embryonic zebrafish models of doxorubicin-, adrenaline- and terfenadine-induced cardiotoxicity with unified dosing regimen which eventually enabled head-to-head comparison of the drugs. Subsequently, we determined whether human cardioprotective medications – dexrazoxane, metoprolol, carvedilol and valsartan – are able to manage heart dysfunction in zebrafish. Our results indicated that doxorubicin, adrenaline and terfenadine elicited overt signs of cardiotoxicity in fish, and we further showed that the blockade of the renin-angiotensin system and, to a lesser extent, β-adrenergic system, ameliorated the heart disease in zebrafish. From the drug development standpoint, our work opens the possibility to determine the cardiovascular properties of tested compounds using the rapid and affordable zebrafish model.

Biomedicine & Pharmacotherapy 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, Category: amides-buliding-blocks.

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

Kario, Kazuomi published the artcileAngiotensin receptor-neprilysin inhibitors for hypertension-hemodynamic effects and relevance to hypertensive heart disease, Formula: C24H29N5O3, the publication is Hypertension Research (2022), 45(7), 1097-1110, database is CAplus and MEDLINE.

A review. Angiotensin receptor-neprilysin inhibitors have multiple beneficial effects on the cardiovascular system. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to effectively reduce ambulatory 24-h blood pressure in patients with hypertension, and improvements in many aspects of hemodynamic function have also been reported. Overall hemodynamic effects on arterial stiffness and nocturnal blood pressure play an important role in the pathogenesis of hypertensive heart disease. Therefore, these could represent mechanistic targets underlying the effects of angiotensin receptor-neprilysin inhibitors on the continuum of cardiovascular disease from hypertension to heart failure. Other potential mechanisms include reductions in circulating volume and sympathetic activity, both of which contribute to the protection against target organ damage and pos. changes in cardiac biomarkers seen during angiotensin receptor-neprilysin inhibitor therapy. The mechanisms of action and beneficial effects of angiotensin receptor-neprilysin inhibitors are complementary to those of a number of other treatment options for hypertension, suggesting the possibility of additive or even synergistic benefits. Based on available data, there are a number of patient groups who will benefit from antihypertensive treatment with an angiotensin receptor-neprilysin inhibitor, including those with salt-sensitive hypertension, structural hypertension, resistant hypertension, and hypertension in the presence of heart failure. Overall, angiotensin receptor-neprilysin inhibitors regulate blood pressure and pulse pressure via multiple mechanisms and provide cardiovascular protection. This provides an option for effective intervention early in the vicious cycle of elevated blood pressure and central pressures with progression toward heart failure that should help to address the growing worldwide heart failure epidemic.

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, Formula: C24H29N5O3.

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

Ding, Yuanyuan published the artcileEffects of Metoprolol Succinate Combined with Entresto on Cardiac Function Indexes and Coagulation Function in Patients with Congestive Heart Failure., Computed Properties of 137862-53-4, the publication is Computational and mathematical methods in medicine (2022), 9765884, database is MEDLINE.

Objective: To investigate the effects of metoprolol succinate combined with Entresto (Sacubitril Valsartan Sodium Tablets) on cardiac function and coagulation function in patients with congestive heart failure (CHF). Methods: About 120 patients with CHF treated from April 2018 to April 2021 were enrolled in our hospital. The patients were arbitrarily assigned into control group and study group. The control group was cured with metoprolol succinate sustained-release tablets, and the study group was cured with metoprolol succinate sustained-release tablets combined with Entresto. The curative effect, cardiac function, vascular endothelial function, oxidative stress, and coagulation function were compared. Results: First of all, we compared the general data, and there exhibited no difference in age, sex, course of disease, hypertension, coronary heart disease, diabetes, atrial fibrillation, and other general data (P > 0.05). Second, we compared the clinical efficacy. The effective rate of the study group (98.33%) was higher (90.00%) (P < 0.05). There exhibited no significant difference in cardiac function indexes before treatment, but after treatment, LVEF increased, LVESD and LVEDD decreased, LVESD and LVEDD in the study group were lower, and LVEF in the study group was higher (P < 0.05). Before treatment, there exhibited no significant difference in vascular endothelial function. However, the levels of CGRP and ET increased and the level of NO decreased, and the level of NO in the study group was lower, while the levels of CGRP and ET in the study group were higher after treatment (P < 0.05). There exhibited no significant difference in oxidative stress indexes before treatment, however, the levels of GSH-Px and SOD increased and the levels of MDA decreased after treatment, while the level of MDA in the study group was lower, while the levels of GSH-Px and SOD in the study group were higher (P < 0.05). Finally, we compared the indexes of blood coagulation function. There exhibited no significant difference before treatment, but after treatment, the levels of APTT, PT, and FIB decreased, and the levels of APTT, PT, and FIB in the study group were lower (P < 0.05). Conclusion: Clinical practice demonstrated that LVESD and LVEDD decreased and LVEF increased after treatment with Entresto combined with metoprolol in CHF patients, which can effectively facilitate cardiac function and vascular endothelial function, reduce oxidative stress reaction, and improve blood coagulation indexes, suggesting that Entresto combined with metoprolol can improve ventricular remodeling with good safety.

Computational and mathematical methods in 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, Computed Properties of 137862-53-4.

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

Wang, Shiru published the artcileSuspect screening to support source identification and risk assessment of organic micropollutants in the aquatic environment of a Sub-Saharan African urban center, Safety of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is Water Research (2022), 118706, database is CAplus and MEDLINE.

Organic micropollutants (OMPs) are contaminants of global concern and have garnered increasing attention in Africa, particularly in urban and urbanizing areas of Sub-Saharan Africa (SSA). In this work, we coupled suspect screening enabled by liquid chromatog.-high-resolution mass spectrometry (LC-HRMS) with multivariate anal. to characterize OMPs in wastewater, surface water, and groundwater samples collected from Kampala, the capital and largest city of Uganda. Suspect screening prioritized and confirmed 157 OMPs in Kampala samples for target quantification. Many OMPs detected in Kampala samples occurred within concentration ranges similar to those documented in previous studies reporting OMP occurrence in SSA, but some have never or rarely been quantified in environmental water samples from SSA. Hierarchical cluster anal. established the source-related co-occurrence profiles of OMPs. Partial least squares regression and multiple linear regression analyses further pinpointed the concentration of nitrate and the content of a fluorescent organic matter component with excitation/emission maxima around 280/330 nm as predictors for the sample-specific cumulative concentrations of OMPs, suggesting the likely contribution of diffuse runoff and wastewater discharges to OMP occurrence in the aquatic environment of Kampala. Parallel calculations of exposure-activity ratios and multi-substance potentially affected fractions provided insights into the potential for biol. effects associated with OMPs and highlighted the importance of expanded anal. coverage for screening-level risk assessments. Overall, our study demonstrates a versatile database-driven screening and data anal. methodol. for the multipronged characterization of OMP contamination in a representative SSA urban center.

Water 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 C7H5ClN2S, Safety 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

Mastrangelo, M. M. published the artcileOccurrence and accumulation of pharmaceutical products in water and biota of urban lowland rivers, Application In Synthesis of 137862-53-4, the publication is Science of the Total Environment (2022), 154303, database is CAplus and MEDLINE.

We evaluated the distribution of eleven groups of pharmaceutically active compounds (PhACs) in surface waters and biota of different trophic levels, in five sites of two lowland urban rivers in Argentine. Twenty-nine out of 39 PhACs and two metabolites were detected in at least one water sample (2-9622 ng/L), eleven detected in biofilms (1-179 ng/g d.w.) and eight in the macrophyte Lemna gibba (4-112 ng/g d.w). The two more polluted sites had a similar distribution of the main groups of compounds In surface waters, the largest concentrations were for the analgesic acetaminophen (9622 ng/L), the antibiotic sulfamethoxazole (326 ng/L), the antihypertensive valsartan (963 ng/L), the β-blocking agent atenolol (427 ng/L), the diuretic hydrochlorothiazide (445 ng/L) and the psychiatric drug carbamazepine (99 ng/L). The antibiotic ciprofloxacin exhibited the highest concentration in the biofilm (179 ng/g d.w.) and in the macrophyte L. gibba (112 ng/g d.w.) Several compounds were detected in the water but not in the biota (e.g., codeine and bezafibrate), and others (e.g., azithromycin and citalopram) were found in the biota but not in the surface water. Significant bioaccumulation factors (>1000 L/kg d.w.) were obtained for venlafaxine and ciprofloxacin in biofilm. Our results show that PhACs may accumulate in several biol. compartments. Within an environmental compartment, similar PhACs profile and concentrations were found in different sites receiving urban pollution. Among different compartments, biofilms may be the most suitable biota matrix to monitor the immediate reception of PhACs in the biota. Our results indicate that the presence of PhACs in urban rivers and their accumulation in the biota could be incorporated as symptoms of the urban stream syndrome.

Science of the Total Environment 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

Peikert, Alexander published the artcileEffects of sacubitril/valsartan versus valsartan on renal function in patients with and without diabetes and heart failure with preserved ejection fraction: insights from PARAGON-HF, Quality Control of 137862-53-4, the publication is European Journal of Heart Failure (2022), 24(5), 794-803, database is CAplus and MEDLINE.

Diabetes is associated with a faster rate of renal function decline in patients with heart failure (HF). Sacubitril/valsartan attenuates the deterioration of renal function to a greater extent in patients with diabetes and HF with reduced ejection fraction compared with renin-angiotensin system inhibitors alone. We assessed whether the same may be true in HF with preserved ejection fraction (HFpEF). In the PARAGON-HF trial in patients with HF and left ventricular ejection fraction of ≥45% (n = 4796), we characterized the effects of sacubitril/valsartan on changes in estimated glomerular filtration rate (eGFR) over a period of 192 wk, and on the pre-specified renal composite outcome (eGFR reduction of ≥50%, end-stage renal disease, or death attributable to renal causes) in patients with (n = 2388) and without diabetes (n = 2408). The decline in eGFR was greater in patients with diabetes than in those without (-2.6 vs. -1.7 mL/min/1.73 m2 per yr, p < 0.001), regardless of treatment assignment. Sacubitril/valsartan attenuated decline in eGFR similarly in patients with (-2.2 vs. -2.9 mL/min/1.73 m2 per yr, p = 0.001) and without diabetes (-1.5 vs. -2.0 mL/min/1.73 m2 per yr, p = 0.006) (pinteraction for difference in eGFR slopes = 0.40). Compared with valsartan, sacubitril/valsartan reduced the renal composite outcome similarly in patients without diabetes (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.19-0.91) and those with diabetes (HR 0.54, 95% CI 0.33-0.89; pinteraction = 0.59), as well as across a range of baseline glycated Hb (pinteraction = 0.71). Sacubitril/valsartan, compared with valsartan, attenuates the decline of eGFR and reduces clin. relevant kidney events similarly among patients with HFpEF with and without diabetes.

European Journal of Heart Failure 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

Pooventhiran, T. published the artcileHydrogen bonds between valsartan and solvents (water and methanol): Evidences for solvation dynamics using local energy decomposition and abinitio molecular dynamics analysis, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is Journal of Molecular Liquids (2022), 118856, database is CAplus.

The change in Gibbs energy when an ion or mol. moves from a vacuum to a solvent is known as solvation energy and solvation is the process of attracting and associating mols. of a solvent with mols. or ions of a solute. Valsartan belongs to the class of drugs known as angiotensin II inhibitors. It is primarily used to treat excessive blood pressure, congestive heart failure and improve the odds of living longer after a heart attack. The main aim of this paper is to study how solvent mols. like water and methanol interact with valsartan. The systems are optimized using the level DFT/B3LYP cc-pVDZ and this geometry was used for Natural bond orbital (NBO), bin-covalent interactions (NCI), and wavefunction assay. PBE0-D3/def2-TZVP is used to perform abinitio mol. dynamics (AIMD) simulations and DLPNO-CCSD(T) for Local Energy Decomposition (LED). Valsartan can produce five fragments: biphenylmethane-, Bu, isopropyl-, N-acyl-Nmethylglycine- and tetrazole, and bond energy (change in enthalpy) is 2451.11 kcal/mol. NBO shown orbital energies of valsartan in a vacuum and its complexes are in order of oxygen electron pairs is valsartan-water > valsartan-methanol > valsartan; similarly, nitrogen electron pairs valsartan-methanol > valsartan > valsartan-water and carbon electron pairs valsartan-water = valsartan-methanol > valsartan. NCI explains the noncovalent interactions of valsartan in vacuum and valsartan with water and methanol (complex) mols.; inter and intra interactions of them. Binding energies of interactions and total binding energies indicated that valsartan-water is of lower energy with more stability than valsartan-methanol is higher energy with less stable. AIMD of valsartan-water is greater simulations and valsartan-methanol is poor simulations between them.

Journal of Molecular Liquids 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

Guion-Firmin, Julia published the artcileDiarrhea and angiotensin II receptor blockers: Is there any difference between the different drugs?, Synthetic Route of 137862-53-4, the publication is Fundamental & Clinical Pharmacology (2022), 36(2), 443-447, database is CAplus and MEDLINE.

Diarrhea is an adverse drug reaction (ADR) widely reported with olmesartan, an angiotensin II receptor blocker (ARB). Isolated case reports described this ADR with other ARBs. The present study was performed to investigate if, among the different ARBs, some drugs are more at risk of diarrhea than others. Using VigiBase, the WHO pharmacovigilance database, we performed a disproportionality anal. (case/noncase study). Cases were reports with the MedDRA PT term << diarrhea >> and noncases all other reports registered during the same period in Vigibase from Apr. 6, 1995 to Dec. 31, 2020. After comparison of ARBs and angiotensin converting enzyme inhibitors (ACEIs), the main anal. was a comparison of the diarrhea reporting risk between each ARB and the seven other ARBs. Results are reported as reporting odds ratio (ROR) adjusted on age, gender, exposure to antihypertensive, and antidiabetic drugs with their 95% confidence interval. Among the 22,429,334 deduplicated reports registered in VigiBase during the study period, 73,507 involved ARBs, including 2119 diarrhea. The reporting risk of diarrhea was higher with ARBs than with ACEIs (ROR = 2.06 (1.55-2.17)). Diarrhea with ARBs mainly occurred in females with a mean age of 65 years. After exclusion of olmesartan (to minimize a notoriety bias), two ARBs were significantly associated with diarrhea: eprosartan (ROR = 1.93 (1.32-2.72) and telmisartan ROR = 1.41 (1.23-1.62)) but not the six others. The present study found first that diarrhea is more frequently reported with ARBs than with ACEIs and second that the risk of diarrhea differs according to the different ARBs. Diarrhea with ARBs is not a class effect.

Fundamental & Clinical 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, Synthetic Route of 137862-53-4.

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

Guion-Firmin, Julia published the artcileDiarrhoea with the angiotensin receptor neprilysin inhibitor sacubitril + valsartan: A pharmacovigilance study, COA of Formula: C24H29N5O3, the publication is Fundamental & Clinical Pharmacology (2022), 36(2), 378-389, database is CAplus and MEDLINE.

Diarrhoea is an adverse drug reaction of the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril + valsartan. It was also described with olmesartan and more recently with other angiotensin receptor blockers. The study was performed to compare diarrhoea reports in pharmacovigilance databases with sacubitril + valsartan and valsartan. The study used reports of diarrhoea with the ARNI sacubitril + valsartan registered: first in the French PharmacoVigilance Database (FPVD) and second in Vigibase, the WHO Global Individual Case Safety Report database. After description of the main characteristics, disproportionality analyses were performed. Results are reported as reporting odds ratios (ROR) with 95% confidence interval. We found 29 reports of diarrhoea with sacubitril + valsartan in the FPVD and 686 in Vigibase. With sacubitril + valsartan, diarrhoea occurred more frequently in males around 70 years with a median delay of 3 days. With valsartan, diarrhoea occurred more frequently in females around 68 years with a median delay of 0.5 days. In the FPVD, a significant association was found with sacubitril + valsartan in comparison with valsartan alone before (ROR = 8.78 [5.19-14.85]) and after (ROR = 11.19 [5.89-21.25]) exclusion of concomitant drugs known to be associated with diarrhoea. A significant association was also found in Vigibase after adjustment on age, sex, reporter and its location (ROR = 1.31 [1.14-1.50]). Diarrhoea reported with sacubitril + valsartan has marked differences in gender, delay of occurrence and frequency of reporting in comparison with diarrhoea with valsartan. From a pharmacodynamic point of view, these results suggest a specific role of sacubitril in diarrhoea.

Fundamental & Clinical 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, COA of Formula: C24H29N5O3.

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

Barman, Hasan Ali published the artcileImpact of Sacubitril/Valsartan on Lipid Parameters in Patients with Heart Failure with Reduced Ejection Fraction, Product Details of C24H29N5O3, the publication is Clinical Drug Investigation (2022), 42(6), 533-540, database is CAplus and MEDLINE.

Abstract: Background and Objective: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has been shown to significantly reduce cardiovascular mortality, heart failure hospitalizations, and all-cause mortality in patients with heart failure with reduced ejection fraction. This study aims to investigate the long-term impact of the sacubitril/valsartan combination on lipid parameters in patients with heart failure with reduced ejection fraction. Methods: For this single-center retrospective cross-sectional study, data of patients using sacubitril/valsartan because of heart failure with reduced ejection fraction were collected. In addition to routine controls, the patients′ lipid levels were measured at 3-mo intervals. The parameters that were obtained over 3 years included total cholesterol, high-d. lipoprotein cholesterol, triglyceride, and N-terminal pro-B-type natriuretic peptide levels. Results: A total of 192 patients with a functional capacity New York Heart Association II-V, and who were using sacubitril/valsartan because of heart failure with reduced ejection fraction, were included in this study. Independent of statin use, there was a decrease in total cholesterol levels (196.1 ± 44.8 mg/dL vs 161.5 ± 41.7 mg/dL, p < 0.001) and triglyceride levels (159.1 ± 10.4 mg/dL vs 121.4 ± 6.9 mg/dL, p < 0.001), and there was an improvement in high-d. lipoprotein cholesterol levels (44.9 ± 1.9 mg/dL vs 48.2 ± 2.4 mg/dL, p < 0.001) when comparing baseline levels with third-year levels. Conclusions: Sacubitril/valsartan in patients with heart failure with reduced ejection fraction, independent of statin use, may cause a decrease in total cholesterol and triglyceride levels and an improvement in high-d. lipoprotein cholesterol levels.

Clinical Drug Investigation 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