Tag: M.W=400-450

Arruda-Junior, Daniel F. published the artcileUnraveling the interplay between dipeptidyl peptidase 4 and the renin-angiotensin system in heart failure, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is Life Sciences (2022), 120757, database is CAplus and MEDLINE.

Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacol. effects rather than being additive. This study tested the hypothesis that combining an inhibitor of DPP4 with an angiotensin II (Ang II) receptor blocker does not provide addnl. cardioprotection compared to monotherapy in heart failure (HF) rats. Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were assigned into four groups and received vehicle (water), vildagliptin, valsartan, or both drugs, for four weeks by oral gavage. Vildagliptin and valsartan in monotherapy reduced LV hypertrophy, alleviated cardiac interstitial fibrosis, and improved systolic and diastolic function in HF rats, with no addnl. effect of combination treatment. HF rats displayed higher cardiac and serum DPP4 activity and abundance than sham. Surprisingly, not only vildagliptin but also valsartan in monotherapy downregulated the catalytic function and expression levels of systemic and cardiac DPP4. Moreover, vildagliptin and valsartan alone or in combination comparably upregulate the components of the cardiac ACE2/Ang-(1-7)/MasR while downregulating the ACE/Ang II/AT1R axis. Vildagliptin or valsartan alone is as effective as combined to treat cardiac dysfunction and remodeling in exptl. HF. DPP4 inhibition downregulates classic RAS components, and pharmacol. RAS blockade downregulates DPP4 in the heart and serum of HF rats. This interplay between DPP4 and RAS may affect HF progression and pharmacotherapy.

Life Sciences 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

Bahgat, Eman A. published the artcileDevelopment and validation of eco-friendly micellar organic solvent-free HPLC method for the simultaneous determination of some antihypertensive combinations, Computed Properties of 137862-53-4, the publication is Microchemical Journal (2022), 107740, database is CAplus.

To minimize the environmental impacts of using organic solvent without affecting the chromatog. performance, alternatives had to be utilized to decrease such pollution. Combination of sodium dodecyl sulfate (SDS) with polyoxyethylene-23-lauryl ether (Brij-35) could be incorporated as a green alternative for using organic solvents as mobile phases in HPLC separation systems. In this research, a micellar organic solvent-free HPLC method have be established for determination of five antihypertensive drugs, namely, captopril (CPT), hydrochlorothiazide (HCT), indapamide (IND), valsartan (VAL) and carvedilol (CAR). The most favorable conditions were validated using mobile phase consists of 0.1 mol/L SDS, 0.03 mol/L Brij-35, adjusted at pH 2.8 using ortho-phosphoric acid on symmetry C18 column and detection at 210 nm. The flow rate was sudden increased from 1.2 to 1.5 mL/min after two minutes and the total separation run time was nine minutes. The method was successfully applied to determine four different combinations of the analytes in bulk and their pharmaceutical dosage forms. Method validation was done according to International Conference of Harmonization guidelines. At linearity range of 5-100μg/mL for CPT, HCT and CAR, 8 – 160μg/mL for VAL, and 2 – 40μg/mL for IND, high accuracy results were found. Moreover, the coefficient of the variation of the points of the calibration curve being below 2% indicating precise method. The LLOQ was (4.88μg/mL) for CPT, (4.89μg/mL) for HCT and CAR, (7.91μg/mL) for VAL, and (1.81μg/mL) for IND. The method’s greenness was determined with the help of an eco-scale scoring method, Green Anal. Procedure Index, and Anal. Greenness Calculator and the proposed method was found to be an excellent green methodol.

Microchemical 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, Computed Properties of 137862-53-4.

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

D’Amario, Domenico published the artcileAssociation between dosing and combination use of medications and outcomes in heart failure with reduced ejection fraction: data from the S wedish Heart Failure Registry, Application In Synthesis of 137862-53-4, the publication is European Journal of Heart Failure (2022), 24(5), 871-884, database is CAplus and MEDLINE.

To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of renin-angiotensin system inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi) and β-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction. Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to Dec. 2018, with ejection fraction <40% and duration of HF ≥90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76-0.91) with <50% of TD, 0.78 (0.71-0.86) with 50%-99%, and 0.73 (0.67-0.80) with ≥100% of TD. Compared with no use of β-blockers, the adjusted HR (95% CI) was 0.86 (0.76-0.91), 0.81 (0.74-0.89) and 0.74 (0.68-0.82) with <50%, 50%-99% and ≥100% of TD, resp. Patients receiving both an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a β-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or β-blocker, even if this was at ≥100% of TD. Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and β-blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD.

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, Application In Synthesis of 137862-53-4.

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

Kober, Gerhard published the artcileModeling Medical Guidelines by Prova and SHACL Accessing FHIR/RDF. Use Case: The Medical ABCDE Approach., Related Products of amides-buliding-blocks, the publication is Studies in health technology and informatics (2022), 59-66, database is MEDLINE.

Decision-making based on so-called medical guidelines supported by semantic AI solutions is an essential and significant task for medical personnel in both a pre-clinical setting and an inner-clinical environment. Semantic representations of medical guidelines and Fast Healthcare Interoperability Resources (FHIR) using Semantic Web technologies, i.e., Resource Description Framework (RDF), rules (RuleML and Prova), and Shape Constraint Language (SHACL), provide a semantic knowledge base for the decision-making process and ease technical implementation and automation tasks. Current medical decision support systems lack Semantic Web integration using FHIR-RDF representations as a data source. In this paper, we implement a particular medical guideline using two different approaches: Prova [8] and SHACL [13]. We generate a series of raw FHIR-data for a selected guideline, the ABCDE approach, and compare the implemented two programs’ (Prova and SHACL) results. Both approaches deliver the same results in terms of content. Both may be used within a distributed medical environment depending on the need of organizations.

Studies in health technology and informatics 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, Related Products of amides-buliding-blocks.

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

Selak, Ana published the artcileEcotoxicological aspects related to the occurrence of emerging contaminants in the Dinaric karst aquifer of Jadro and Zrnovnica springs, COA of Formula: C24H29N5O3, the publication is Science of the Total Environment (2022), 153827, database is CAplus and MEDLINE.

Karst aquifers are globally important source of drinking water and harbor specific ecosystems that are vulnerable to anthropogenic contamination. This paper provides insights into the occurrence and ecotoxicol. characterization of 21 emerging contaminants (ECs) detected in the karst catchment of Jadro and Zrnovnica springs (Dinarides, Croatia). Karst springs used for water supply, surface water, and groundwater were sampled during seven campaigns. The ECs concentration levels ranged from 0.3 ng/L (tramadol in Jadro spring) to 372 ng/L (1H-benzotriazole in Cetina River). DEET was the most frequently detected ECs with an average concentration of around 50 ng/L in both surface water and groundwater. To prioritise detected ECs, their persistence (P), bioaccumulation (B), mobility (M) and toxicity (T) were assessed based on in silico strategy for PBT assessment and recently developed REACH PMT guidelines. PBT scores ranging below the threshold of 0.5, indicated non-PBT compounds of expected low concern. However, only 4 out of 21 detected ECs were not assessed as PMT/vPvM. Concerningly, 20 ECs were categorised as very mobile. Karst springs exhibited larger proportions of ECs meeting PMT/vPvM criteria than surface water. To characterize the contamination extent and estimate the incidence of adverse effects of detected ECs, a preliminary environmental risk assessment (ERA) was conducted. Most ECs posed no environmental risk with RQ values predominantly below 0.01. The total risk quotient RQsite accentuated Cetina River as having the highest risk compared to other sampling sites. This is the first study on ECs in Croatian karst, contributing to a growing need to understand the impacts of emerging contaminants in karst aquifers, which are still largely unexplored.

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 C6H5F4NO3S, COA of Formula: C24H29N5O3.

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

Thonsgaard, Simon published the artcileCirculating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men., SDS of cas: 137862-53-4, the publication is Clinical chemistry (2022), 68(5), 713-720, database is MEDLINE.

BACKGROUND: C-type natriuretic peptide (CNP) is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). We aimed to determine whether angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP). METHODS: We included 9 and 10 healthy young men in 2 randomized crossover trials with sacubitril/valsartan vs control (Trial 1) and sacubitril/valsartan and sitagliptin vs sitagliptin (Trial 2). The participants were randomized to a single dose of sacubitril/valsartan (194/206 mg) or control at the first visit 30 min prior to a standardized meal intake. We obtained blood samples at 12 time points over 5 h and measured plasma concentrations of NT-proCNP in both trials and CNP in Trial 2. RESULTS: NT-proCNP concentrations increased 3.5 h after sacubitril/valsartan treatment, and at 4.5 h concentrations were 42% and 65% higher compared with control in Trial 1 and Trial 2, respectively. The total area under the curve (tAUC)15-270 min was 22% higher (P = 0.007) in Trial 1 and 17% higher with treatment (P = 0.017) in Trial 2. Concentrations of bioactive CNP followed a similar temporal pattern with an increase of 93% at 4.5 h and a 31% higher tAUC15-270 min compared with control (P = 0.001) in Trial 2. CONCLUSIONS: Sacubitril/valsartan augments circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men. The increase in bioactive CNP is most likely caused by de novo synthesis and secretion rather than diminished breakdown through neprilysin inhibition.ClinicalTrials.gov registration number NCT03717688.

Clinical chemistry 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 C12H17NS2, SDS of cas: 137862-53-4.

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

Kim, Byung Sik published the artcileSacubitril/valsartan reduces endoplasmic reticulum stress in a rat model of doxorubicin-induced cardiotoxicity, Formula: C24H29N5O3, the publication is Archives of Toxicology (2022), 96(4), 1065-1074, database is CAplus and MEDLINE.

Abstract: The induction of endoplasmic reticulum (ER) stress has been reported as a key contributor to the cardiotoxicity of doxorubicin. Previous in vitro and in vivo studies suggest that sacubitril/valsartan, a novel angiotensin receptor-neprilysin inhibitor, could be effective against doxorubicin-induced cardiotoxicity. However, the precise mechanisms are not fully understood. Therefore, we investigated whether the cardioprotective effects of sacubitril/valsartan are associated with ER stress modulation in a rat model of doxorubicin-induced cardiotoxicity. Male Sprague-Dawley rats were treated with i.p. injections of doxorubicin (15 mg/kg; cumulative) or saline for 3 wk. From the day before the first treatment, control animals were gavaged daily with water (n = 8), whereas doxorubicin-treated animals were gavaged daily with water (n = 8) or sacubitril/valsartan (60 mg/kg/day; n = 8) for 6 wk. Echocardiog. was performed 6 wk after the initiation of doxorubicin. In addition, serum troponin I and N-terminal brain natriuretic peptide levels were determined, and the extent of apoptosis and protein levels related to ER stress in the cardiac tissue and doxorubicin-treated H9c2 cardiomyocytes were analyzed. Sacubitril/valsartan significantly reduced doxorubicin-induced cardiac dysfunction and apoptosis in the myocardium. In addition, sacubitril/valsartan significantly downregulated the expression levels of proteins related to apoptosis and ER stress, including BAX, caspase 3, GRP78, PERK, IRE-1α, ATF-6, eIF-2α, ATF-4, and CHOP, in the myocardium of a rat model of doxorubicin-induced cardiotoxicity in vivo and doxorubicin-treated H9c2 cardiomyocytes in vitro. Sacubitril/valsartan significantly alleviated doxorubicin-induced cardiotoxicity, which may be associated with the reduction of ER stress.

Archives of Toxicology 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

Perrone-Filardi, Pasquale published the artcileRenin-angiotensin-aldosterone system inhibition in patients affected by heart failure: efficacy, mechanistic effects and practical use of sacubitril/valsartan. Position Paper of the Italian Society of Cardiology, COA of Formula: C24H29N5O3, the publication is European Journal of Internal Medicine (2022), 8-16, database is CAplus and MEDLINE.

A review. Renin-angiotensin-aldosterone system (RAAS) inhibition is a mainstay of the pharmacol. treatment of heart failure with reduced ejection fraction (HFrEF). In the last years RAAS blockade has been improved by the introduction of the Angiotensin Receptor-Neprilysin Inhibitor (ARNI) sacubitril/valsartan, that combines RAAS inhibition with the block of neprilysin, boosting the pos. effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a significant advantage of sacubitril/valsartan over enalapril on the reduction of cardiovascular (CV) mortality and heart failure hospitalizations rates. Then, several randomized clin. trials and observational studies investigated its role in different clin. settings and its efficacy has been fully recognized in the most recent HFrEF European and USA guidelines. The effects of sacubitril/valsartan on major CV outcomes are associated with reduction of NT-proBNP levels and reverse cardiac remodeling and mitral regurgitation, recognized as one of the mechanistic effects of the drug explaining the favorable prognostic effects. A careful evaluation of patients′ clin. profile is relevant to implement the use of ARNI in the clin. practice and to obtain the maximal treatment efficacy. The present Position Paper reports the opinion of the Italian Society of Cardiol. on the optimal blockade of the RAAS system in HF patients with the aim of fostering widespread implementation of scientific evidence and practice guidelines in the medical community.

European Journal of Internal 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, COA of Formula: C24H29N5O3.

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

Bokulic, Ana published the artcileIsolation of MDCK cells with low expression of mdr1 gene and their use in membrane permeability screening, Quality Control of 137862-53-4, the publication is Acta Pharmaceutica (Warsaw, Poland) (2022), 72(2), 275-288, database is CAplus.

The Madin-Darby canine kidney (MDCK) cell line is frequently used for permeability screening in drug discovery. It contains endogenous transporters, most prominently canine multidrug resistance P-glycoprotein (Mdr1), which can interfere with studies of P-glycoprotein substrate assessment and permeability measurements. Because MDCK wild type (WT) is genetically heterogeneous, an isolation procedure was investigated in this study to obtain the subclonal line with low P-glycoprotein expression. The best clone obtained had up to 3-fold lower amprenavir efflux and P-glycoprotein expression in comparison to WT. Of 12 standard compounds tested that exhibited active efflux in WT cells, 11 showed a decrease in efflux in the isolated clone. However, the decrease was not below the cut-off value of 2, indicating residual P–glycoprotein activity. Clone isolation via the limiting dilution method, combined with bidirectional amprenavir permeability for clone selection, successfully identified MDCK clones with substantially lower P-glycoprotein efflux and has been demonstrated as a useful tool for assessing passive permeability in early drug discovery.

Acta Pharmaceutica (Warsaw, Poland) 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

Escobedo, Ericson published the artcileActivation of hydrogen peroxide, persulfate, and free chlorine by steel anode for treatment of municipal and livestock wastewater: Unravelling the role of oxidants speciation, Product Details of C24H29N5O3, the publication is Water Research (2022), 118305, database is CAplus and MEDLINE.

Despite the extensive application of electrochem. advanced oxidation processes (EAOPs) in wastewater treatment, the exact speciation of oxidants and their effects on pollutants removal efficiency, byproducts formation, and effluent toxicity are largely unknown. In this study, galvanostatic steel anodes were used to drive the electrochem. activation of hydrogen peroxide (EAHP), persulfate (EAP), and free chlorine (EAFC), for industrial-scale treatment of municipal and livestock wastewater with a focus on micropollutants and transformation products (MTPs) and effluent toxicity. Response surface methodol. determined the optimized conditions for each treatment towards total organic carbon ([TOC]₀ = 180 mg/L) removal at pH 3.0: persulfate dose = 0.12 mmol/min, 26.5 mA/cm²; free chlorine dose = 0.29 mmol/min, 37.4 mA/cm²; H₂O₂ dose = 0.20 mmol/min, 45 mA/cm². Probe-compound degradation revealed that HO^•, SO^•-₄ and Fe^IVO²⁺ species were simultaneously generated in EAP, whereas HO^• and Fe^IVO²⁺ were the principal oxidants in EAHP and EAFC, resp. Samples were analyzed via liquid and gas chromatog. in non-target screening (NTS) mode to monitor the generation or removal of MTPs and byproducts including compounds that have not been reported previously. The speciation of oxidants, shifted in presence of halide ions (Cl^–, Br^–) in real wastewater samples, significantly affected the mineralization efficiency and byproduct formation. The production of halogenated byproducts in EAFC and EAP substantially increased the effluent toxicity, whereas EAHP provided non-toxic effluent and the highest mineralization efficiency (75 – 80%) to be nominated as the best strategy.

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 C24H29N5O3, Product Details of C24H29N5O3.

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