Tag: M.W=400-450

Lenschow, Iara Cristina Schmucker published the artcileBall-milled valsartan and its combination with mannitol: the case of drug polyamorphism, Formula: C24H29N5O3, the publication is Journal of Thermal Analysis and Calorimetry (2022), 147(16), 8765-8777, database is CAplus.

Valsartan (VAL) is a drug that has low water solubility and low oral bioavailability. Unlike most drugs, bulk VAL has unusual solid-state properties, including the phenomenon of polyamorphism. Furthermore, surprisingly, obtaining the neat VAL in a completely amorphous form does not increase its solubility In this study, the influence of different ball milling conditions (milling time and speed) on dissolution rate, thermoanal. and solid-state properties of VAL was studied. The influence of the association of VAL with the hydrophilic carrier mannitol (as phys. mixtures and solid dispersions, at different drug/carrier ratios) on drug dissolution, thermoanal. and solid-state properties was also evaluated. Bulk VAL, milled-VAL and phys. mixtures and solid dispersions (SDs) of the drug with mannitol were characterized by differential scanning calorimetry, powder X-ray diffraction anal. and Fourier transformed IR spectroscopy. Ball milling the neat drug originated self-agglomerated particles, with lower dissolution rate than bulk VAL, and the conversion of VAL from a more ordered amorphous form to another fully amorphous and less soluble form. The same conversion occurred after ball milling of VAL with mannitol (SDs). This change in VAL polyamorphic forms resulting from the ball-milling process had not yet been described in other studies. The highest proportion of mannitol tested (VAL: mannitol 1:3 m/m) promoted a greater increase in the dissolution rate of the drug. A phys. mixture prepared in the same composition showed a dissolution profile similar to these SDs. These results demonstrated that the simple association of VAL with mannitol is sufficient to improve its dissolution rate, without changing the solid state of drug.

Journal of Thermal Analysis and Calorimetry 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

Hammerman, Ariel published the artcileDapagliflozin Versus Sacubitril-Valsartan to Improve Outcomes of Patients with Reduced Ejection Fraction and Diabetes Mellitus, Quality Control of 137862-53-4, the publication is American Journal of Cardiovascular Drugs (2022), 22(3), 325-331, database is CAplus and MEDLINE.

Abstract: Background: Comorbid heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (DM) is associated with a very high risk of HF events. Sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, improve HF outcomes in these patients, but their comparative value for money in this patient population has not yet been determined Objective: We aimed to compare the cost needed to treat (CNT) to avoid an HF event with each drug. Methods: CNT was estimated by multiplying the annualized number needed to treat (NNT) to prevent one HF event by the annual cost of each therapy. HF events were defined as the first event of hospitalization for HF or cardiovascular mortality. Drug efficacy data were extracted from published secondary analyses of patients with DM in the DAPA-HF and PARADIGM-HF trials. Drug costs were estimated as 75‰ of the 2021 US National Average Drug Acquisition Cost listing. Sensitivity anal. was performed on parameters that may have affected the CNT. Results: The annualized NNT was 24 (95‰ confidence interval [CI] 16-54) for dapagliflozin and 57 (95‰ CI 31-433) for the ARNI. At an annual cost of $US4523 and 5099, resp., the CNT was $US108,563 (95‰ CI 72,375-244,267) for dapagliflozin and $US290,671 (95‰ CI 158,084-2,208,079) for the ARNI. Conclusions: Dapagliflozin seems to offer greater value for money than the ARNI for patients with HFrEF and DM. Our results provide support for contemporary guidelines advocating the use of dapagliflozin in these patients.

American Journal of Cardiovascular Drugs 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

Repova, Kristina published the artcileCardiovascular therapeutics: A new potential for anxiety treatment?, Related Products of amides-buliding-blocks, the publication is Medicinal Research Reviews (2022), 42(3), 1202-1245, database is CAplus and MEDLINE.

A review. Besides the well-recognized risk factors, novel conditions increasing cardiovascular morbidity and mortality are emerging. Undesirable emotions and behavior such as anxiety and depression, appear to participate in worsening cardiovascular pathologies. On the other hand, deteriorating conditions of the heart and vasculature result in disturbed mental and emotional health. The pathophysiol. background of this bidirectional interplay could reside in an inappropriate activation of vegetative neurohormonal and other humoral systems in both cardiovascular and psychol. disturbances. This results in circulus vitiosus potentiating mental and circulatory disorders. Thus, it appears to be of utmost importance to examine the alteration of emotions, cognition, and behavior in cardiovascular patients. In terms of this consideration, recognizing the potential of principal cardiovascular drugs to interact with the mental state in patients with heart or vasculature disturbances is unavoidable, to optimize their therapeutic benefit. In general, beta-blockers, central sympatholytics, ACE inhibitors, ARBs, aldosterone receptor blockers, sacubitril/valsartan, and fibrates are considered to exert anxiolytic effect in animal experiments and clin. settings. Statins and some beta-blockers appear to have an equivocal impact on mood and anxiety and ivabradine expressed neutral psychol. impact. It seems reasonable to suppose that the knowledge of a patient’s mood, cognition, and behavior, along with applying careful consideration of the choice of the particular cardiovascular drug and respecting its potential psychol. benefit or harm might improve the individualized approach to the treatment of cardiovascular disorders.

Medicinal Research Reviews 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

Mochizuki, Tatsuki published the artcilePhysiologically-based pharmacokinetic model-based translation of OATP1B -mediated drug-drug interactions from coproporphyrin I to probe drugs, COA of Formula: C24H29N5O3, the publication is Clinical and Translational Science (2022), 15(6), 1519-1531, database is CAplus and MEDLINE.

The accurate prediction of OATP1B-mediated drug-drug interactions (DDIs) is challenging for drug development. Here, we report a physiol.-based pharmacokinetic (PBPK) model anal. for clin. DDI data generated in heathy subjects who received oral doses of cyclosporin A (CysA; 20 and 75 mg) as an OATP1B inhibitor, and the probe drugs (pitavastatin, rosuvastatin, and valsartan). PBPK models of CysA and probe compounds were combined assuming inhibition of hepatic uptake of endogenous coproporphyrin I (CP-I) by CysA. In vivo K_i of unbound CysA for OATP1B (K_i,OATP1B), and the overall intrinsic hepatic clearance per body weight of CP-I (CL_int,all,unit) were optimized to account for the CP-I data (K_i,OATP1B, 0.536 ± 0.041 nM; CL_int,all,unit, 41.9 ± 4.3 L/h/kg). DDI simulation using K_i,OATP1B reproduced the dose-dependent effect of CysA (20 and 75 mg) and the dosing interval (1 and 3 h) on the time profiles of blood concentrations of pitavastatin and rosuvastatin, but DDI simulation using in vitro K_i,OATP1B failed. The Cluster Gauss-Newton method was used to conduct parameter optimization using 1000 initial parameter sets for the seven pharmacokinetic parameters of CP-I (β, CL_int,all, F_aF_g, R_dif, f_bile, f_syn, and v_syn), and K_i,OATP1B and K_i,MRP2 of CysA. Based on the accepted 546 parameter sets, the range of CL_int,all and K_i,OATP1B was narrowed, with coefficients of variation of 12.4% and 11.5%, resp., indicating that these parameters were practically identifiable. These results suggest that PBPK model anal. of CP-I is a promising translational approach to predict OATP1B-mediated DDIs in drug development.

Clinical and Translational Science 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

Arvaniti, Olga S. published the artcileSorption of two common antihypertensive drugs onto polystyrene microplastics in water matrices, Formula: C24H29N5O3, the publication is Science of the Total Environment (2022), 155786, database is CAplus and MEDLINE.

Recent studies have shown the widespread occurrence of microplastics in multiple environmental compartments. When discharged into the aquatic environment, microplastics interact with other chems. acting as vectors of organic and inorganic micropollutants. In the present study, we examined the sorption of two commonly used antihypertensive drugs, valsartan (VAL) and losartan (LOS), onto polystyrene (PS) microplastics and we studied the effects of water matrix, solution’s pH, salinity, and microplastics’ aging on their sorption. According to the results, the sorption of VAL and LOS onto PS is a slow process that reaches equilibrium after 12 days. The sorption of both target micropollutants was pH-dependent and significantly decreased under alk. conditions. The removal of VAL was enhanced in the presence of 100 mM of Ca²⁺ while no statistical significant effects were observed when Na⁺ was added. The increase of salinity either did not affect or decreased the removal of LOS. Lower sorption of both drugs was observed when aged PS was used despite that the sp. surface area for aged PS was 39% higher than pristine. Calculation of the sorption distribution coefficient (Kd) for different water matrixes showed that the increase of matrix complexity inhibited target compounds’ removal and the sorption rate decreased from bottled water > river water ≈ treated wastewater for the two compounds For VAL, the Kd values ranged between 795 ± 63 L/kg (bottled water) and 384 ± 88 L/kg (river water), while for LOS between 4453 ± 417 L/kg (bottled water) and 3078 ± 716 L/kg (treated wastewater). Both VAL and LOS sorption onto PS microplastics can be described by hydrophobic and electrostatic interactions. The current results indicate that PS particles could affect the transportation of antihypertensive drugs in the aquatic environment causing potential adverse effects on the environment and public health.

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, Formula: C24H29N5O3.

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

Brice, Reoyo-Prats published the artcileContinuous degradation of micropollutants in real world treated wastewaters by photooxidation in dynamic conditions, HPLC of Formula: 137862-53-4, the publication is Water Research (2022), 118777, database is CAplus and MEDLINE.

Wastewater is a major issue for the ecosystem because of its considerable quantities, the treatment methods adopted in the large majority of WWTPs, and its level of contamination by various types of pollutants, especially emerging ones. One of the solutions considered to reduce this pressure on water is the reuse of wastewater after treatment for watering green areas, road cleaning, industry, groundwater recharge but also for crop irrigation. This paper proposes to study the capabilities of a photoreactor for the removal of micropollutants contained in wastewater from wastewater treatment plants. The experiments are carried out under dynamic artificial irradiation conditions which can be controlled in order to apply irradiation representative of the sunshine conditions. The experiments aim at treating a real effluent from urban wastewater. On the basis of these data, the photo-oxidation mass capacities expressed per unit of irradiated surface and per day were evaluated. Our results show that the oxidation process acts in a selective and differentiated manner according to the categories of substances and within each category. Some mols. are not or only partially oxidized. Note that the photo-reactor fed continuously with wastewater from wastewater treatment plants containing about 80 substances, is subjected to a typical irradiation setpoint of a sunny day in Apr. This allows to define the instantaneous and daily capacities of the system with respect to the target mols.

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, HPLC of Formula: 137862-53-4.

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

Al-kuraishy, Hayder M. published the artcileThe Prospective Effect of Allopurinol on the Oxidative Stress Index and Endothelial Dysfunction in Covid-19, Synthetic Route of 137862-53-4, the publication is Inflammation (2022), 45(4), 1651-1667, database is CAplus and MEDLINE.

SARS-CoV-2 by the direct cytopathic effect or indirectly through the propagation of pro-inflammatory cytokines could cause endothelial dysfunction (ED) and oxidative stress (OS). It has been reported that OS is triggered by various types of viral infections, including SARS-CoV-2. Into the bargain, allopurinol is regarded as a potent antioxidant that acts through inhibition of xanthine oxidase (XO), which is an essential enzyme of purine metabolism Herein, the present study aimed to find the potential protective effects of allopurinol on the biomarkers of OS and ED in patients with severe Covid-19. This single-center cohort study recruited 39 patients with mild-moderate Covid-19 compared with 41 patients with severe Covid-19. Nineteen patients with severe Covid-19 were on the allopurinol treatment because of underlying chronic gout 3 years ago compared with 22 Covid-19 patients not on this treatment. The recruited patients were allocated into three groups: group I, mild-moderate Covid-19 on the standard therapy (n = 39); group II, severe Covid-19 patients on the standard therapy only (n = 22); and group III, severe Covid-19 patients on the standard therapy plus allopurinol (n = 19). The duration of the study was 3 wk from the time of hospitalization till the time of recovery. In addition, inflammatory biomarkers (D-dimer, LDH, ferritin, CRP, procalcitonin), neutrophil-lymphocyte ratio (NLR), endothelin-1 (ET-1), uric acid and oxidative stress index (OSI), CT scan score, and clin. score were evaluated at the time of admission and discharge regarding the effect of allopurinol treatment adds to the standard treatment of Covid-19. Allopurinol plus standard treatment reduced LDH, ferritin, CRP, procalcitonin, and ET-1 serum level significantly (P < 0.05) compared with Covid-19 patients on standard treatment. Besides, neutrophil (%), lymphocyte (%), and neutrophil-lymphocyte ratio (NLR) were reduced in patients with severe Covid-19 on standard treatment plus allopurinol compared with Covid-19 patients on standard treatment alone (P < 0.01). OSI was higher in patients with severe Covid-19 than mild-moderate Covid-19 patients (P = 0.00001) at admission. At the time of discharge, the oxidative status of Covid-19 patients was significantly improved compared with that at admission (P = 0.01). In conclusion, Covid-19 severity is linked with high OS and inflammatory reaction with ED development. High uric acid in patients with severe Covid-19 is correlated with high OS and inflammatory biomarkers. Allopurinol with standard treatment in patients with severe Covid-19 reduced oxidative and inflammatory disorders with significant amelioration of ED and clin. outcomes.

Inflammation 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

El-Battrawy, Ibrahim published the artcileImpact of sacubitril/valsartan on cardiac arrest event rate. Letter regarding the article ‘Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): design and baseline characteristics’, Product Details of C24H29N5O3, the publication is European Journal of Heart Failure (2022), 24(7), 1324, database is CAplus and MEDLINE.

A polemic in response to Jering et al is given. The article by Jering et al.1 published in this Journal presented an interesting study concept. The study group aimed to study the impact of sacubitril/valsartan treatment in comparison with ramipril on cardiovascular outcome in patients with acute myocardial infarction. Patients are included if left ventricular ejection fraction ≤40% and/or in case of pulmonary congestion.

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, Product Details of C24H29N5O3.

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

El-Awady, Mohamed I. published the artcileDecision-making tree for improving selectivity and sensitivity of sweeping-MEKC determination of hydrophobic analytes: Application to five cardiovascular drugs with greenness assessment, Category: amides-buliding-blocks, the publication is Microchemical Journal (2022), 107792, database is CAplus.

Efficient separation of five cardiovascular drugs has been achieved by a new micellar electrokinetic chromatog. method based on using a general strategy that can be applied for the separation of different hydrophobic analytes, while keeping the highest possible sweeping efficiency and hence the highest possible sensitivity. The studied drugs include valsartan, atorvastatin, ezetimibe, amlodipine, and simvastatin. The separation is accomplished in less than 12 min by applying a basic background electrolyte composed of 10 mM disodium tetraborate buffer of pH 10.5 containing 25 mM SDS and 11% n-propanol at 30 kv. Cromolyn sodium is used as an internal standard Variables that may influence the electrophoretic mobility of the five compounds are investigated. The calibration plots are linear within ranges of 0.5-20.0 μg/mL, 0.5-10.0 μg/mL and 10.0-100.0 μg/mL for valsartan, ezetimibe and simvastatin (at 200 nm) and 1.0-30.0 μg/mL for amlodipine, atorvastatin and simvastatin (at 240 nm). Correlation coefficients are ≥ 0.9997 and detection limits are ranged between 0.12 and 2.05 μg/mL. The developed procedure is successfully utilized to estimate the studied compounds in different pharmaceutical preparations The obtained data are statistically analyzed and evaluated. The greenness profile of the investigated approach has been assessed by a recent assessment tool to ensure the principles of green chem.

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, Category: amides-buliding-blocks.

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

Malnes, Daniel published the artcileOccurrence and mass flows of contaminants of emerging concern (CECs) in Sweden’s three largest lakes and associated rivers, HPLC of Formula: 137862-53-4, the publication is Chemosphere (2022), 133825, database is CAplus and MEDLINE.

Contaminants of emerging concern (CECs) are a concern in aquatic environments due to possible adverse effects on the environment and humans. This study assessed the occurrence and mass flows of CECs in Sweden’s three largest lakes and 24 associated rivers. The occurrence and distribution of 105 CECs was investigated, comprising 71 pharmaceuticals, 13 perfluoroalkyl substances (PFASs), eight industrial chems., four personal care products (PCPs), three parabens, two pesticides, and four other CECs (mostly anthropogenic markers). This is the first systematic study of CECs in Sweden’s main lakes and one of the first to report environmental concentrations of the industrial chems. tri-Bu citrate acetate and 2,2′-dimorpholinyldiethyl-ether. The ∑CEC concentration was generally higher in river water (31-5200 ng/L; median 440 ng/L) than in lake water (36-900 ng/L; median 190 ng/L). At urban lake sites, seasonal variations were observed for PCPs and parabens, and also for antihistamines, antidiabetics, antineoplastic agents, antibiotics, and fungicides. The median mass CEC load in river water was 180 g/day (range 4.0-4300 g/day), with a total mass load of 5000 g/day to Lake Vanern, 510 g/day to Lake Vattern, and 5600 g/day to Lake Malaren. All three lakes are used as drinking water reservoirs, so further investigations of the impact of CECs on the ecosystem and human health are needed.

Chemosphere 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