Month: December 2022

Mueller, Martin published the artcileImpact of co-administered stabilizers on the biopharmaceutical performance of regorafenib amorphous solid dispersions, Quality Control of 1019206-88-2, the publication is European Journal of Pharmaceutics and Biopharmaceutics (2021), 189-199, database is CAplus and MEDLINE.

Poor solubility of drug candidates is a well-known and thoroughly studied challenge in the development of oral dosage forms. One important approach to tackle this challenge is the formulation as an amorphous solid dispersion (ASD). To reach the desired biopharmaceutical improvement a high supersaturation has to be reached quickly and then be conserved long enough for absorption to take place. In the presented study, various formulations of regorafenib have been produced and characterized in biorelevant in-vitro experiments Povidone-based formulations, which are equivalent to the marketed product Stivarga, showed a fast drug release but limited stability and robustness after that. In contrast, HPMCAS-based formulations exhibited excellent stability of the supersaturated solution, but unacceptably slow drug release. The attempt to combine the desired attributes of both formulations by producing a ternary ASD failed. Only co-administration of HPMCAS as an external stabilizer to the rapidly releasing Povidone-based ASDs led to the desired dissolution profile and high robustness. This optimized formulation was tested in a pharmacokinetic animal model using Wistar rats. Despite the promising in-vitro results, the new formulation did not perform better in the animal model. No differences in AUC could be detected when compared to the conventional (marketed) formulation. These data represent to first in-vivo study of the new concept of external stabilization of ASDs. Subsequent in-vitro studies revealed that temporary exposure of the ASD to gastric medium had a significant and long-lasting effect on the dissolution performance and externally administered stabilizer could not prevent this sufficiently. By applying the co-administered HPMCAS as an enteric coating onto Stivarga tablets, a new bi-functional approach was realized. This approach achieved the desired tailoring of the dissolution profile and high robustness against gastric medium as well as against seeding.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about 1019206-88-2. 1019206-88-2 belongs to amides-buliding-blocks, auxiliary class Protein Tyrosine Kinase/RTK,VEGFR, name is 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide hydrate, and the molecular formula is C21H17ClF4N4O4, Quality Control of 1019206-88-2.

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

Dermenci, Alpay published the artcileRh-catalyzed decarbonylation of conjugated ynones via carbon-alkyne bond activation: reaction scope and mechanistic exploration via DFT calculations, Name: N-Methoxy-N-methylisonicotinamide, the publication is Chemical Science (2015), 6(5), 3201-3210, database is CAplus and MEDLINE.

Detailed development of a catalytic decarbonylation of conjugated monoynones to synthesize disubstituted alkynes was described. The reaction scope and limitation has been thoroughly investigated, and a broad range of functional groups including heterocycles were compatible under the catalytic conditions. Mechanistic exploration via DFT calculations has also been executed. Through the computational study, a proposed catalytic mechanism has been carefully evaluated. These efforts are expected to serve as an important exploratory study for developing catalytic alkyne-transfer reactions via carbon-alkyne bond activation.

Chemical Science published new progress about 100377-32-0. 100377-32-0 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N-Methoxy-N-methylisonicotinamide, and the molecular formula is C8H10N2O2, Name: N-Methoxy-N-methylisonicotinamide.

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

Klabunde, Thomas published the artcileAcyl Ureas as Human Liver Glycogen Phosphorylase Inhibitors for the Treatment of Type 2 Diabetes, Computed Properties of 2447-79-2, the publication is Journal of Medicinal Chemistry (2005), 48(20), 6178-6193, database is CAplus and MEDLINE.

Using a focused screening approach, acyl ureas have been discovered as a new class of inhibitors of human liver glycogen phosphorylase (hlGPa). The x-ray structure of screening hit 1 (IC₅₀ = 2 μM) in a complex with rabbit muscle glycogen phosphorylase b reveals that 1 binds at the AMP site, the main allosteric effector site of the dimeric enzyme. A first cycle of chem. optimization supported by x-ray structural data yielded derivative 21, which inhibited hlGPa with an IC₅₀ of 23±1 nM, but showed only moderate cellular activity in isolated rat hepatocytes (IC₅₀ = 6.2 μM). Further optimization was guided by (i) a 3D pharmacophore model that was derived from a training set of 24 compounds and revealed the key chem. features for the biol. activity and (ii) the 1.9 Å crystal structure of 21 in complex with hlGPa. A second set of compounds was synthesized and led to 42 with improved cellular activity (hlGPa IC₅₀ = 53±1 nM; hepatocyte IC₅₀ = 380 nM). Administration of 42 to anesthetized Wistar rats caused a significant reduction of the glucagon-induced hyperglycemic peak. These findings are consistent with the inhibition of hepatic glycogenolysis and support the use of acyl ureas for the treatment of type 2 diabetes.

Journal of Medicinal Chemistry published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C7H5Cl2NO, Computed Properties of 2447-79-2.

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

Zhang, Zeshuai published the artcileSelective N-Monovinylation of Primary Aromatic Amides Using Calcium Carbide as an Alkyne Source, Application In Synthesis of 2447-79-2, the publication is ChemistrySelect (2022), 7(26), e202201463, database is CAplus.

An efficient method for the selective N-monovinylation of primary aromatic amides using calcium carbide as an alkyne source was described. A series of N-vinylbenzamides (enamides) RC(O)NHCH=CH₂ [R = Ph, 2-MeC₆H₄, 4-ClMeC₆H₄, etc.] were readily synthesized by this strategy. The salient features for this protocol were the use of inexpensive, easy-to-handle solid alkyne source, high chemoselectivity, transition metal catalyst-free, good functional group tolerance, and simple work-up procedures. These reactions was also be extended to the gram-scale level.

ChemistrySelect published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C27H39ClN2, Application In Synthesis of 2447-79-2.

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

Scholz, Christian published the artcileAcetylation site specificities of lysine deacetylase inhibitors in human cells, Quality Control of 1011557-82-6, the publication is Nature Biotechnology (2015), 33(4), 415-423, database is CAplus and MEDLINE.

Lysine deacetylases inhibitors (KDACIs) are used in basic research, and many are being investigated in clin. trials for treatment of cancer and other diseases. However, their specificities in cells are incompletely characterized. Here we used quant. mass spectrometry (MS) to obtain acetylation signatures for 19 different KDACIs, covering all 18 human lysine deacetylases. Most KDACIs increased acetylation of a small, specific subset of the acetylome, including sites on histones and other chromatin-associated proteins. Inhibitor treatment combined with genetic deletion showed that the effects of the pan-sirtuin inhibitor nicotinamide are primarily mediated by SIRT1 inhibition. Furthermore, we confirmed that the effects of tubacin and bufexamac on cytoplasmic proteins result from inhibition of HDAC6. Bufexamac also triggered an HDAC6-independent, hypoxia-like response by stabilizing HIF1-α, providing a possible mechanistic explanation of its adverse, pro-inflammatory effects. Our results offer a systems view of KDACI specificities, providing a framework for studying function of acetylation and deacetylases.

Nature Biotechnology published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Quality Control of 1011557-82-6.

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

Hammel, Emily published the artcileImplications of PFAS definitions using fluorinated pharmaceuticals, COA of Formula: C17H14F3N3O2S, the publication is iScience (2022), 25(4), 104020, database is CAplus and MEDLINE.

There are 9,000+ per- and polyfluoroalkyl substances (PFAS) in existence, which makes studying and regulating PFAS individually, or even as small mixtures, infeasible. Multiple PFAS definitions based on structure have been proposed, yet these definitions do not consider the implications for the full suite of organofluorine chems. For example, organofluorine pharmaceuticals, whose use may be essential and are found in human serum and wastewater, are not uniformly identified across all definitions. Using nine definitions prepared by various stakeholders, we screened the 360 organofluorine pharmaceuticals approved and used globally between 1954 and 2021. Definitions ranged in their inclusion of organofluorine pharmaceuticals (1%-100%). The most inclusive definitions include several top prescribed pharmaceuticals, e.g., Prozac and Lipitor. This anal. provides a framework against which organizations can make decisions about how best to proceed when defining PFAS.

iScience published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, COA of Formula: C17H14F3N3O2S.

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, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, 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 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C4H6O3, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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

Liu Limin published the artcileDesign, Synthesis, and Antitumor Activity Evaluation of Trifluoromethyl-Substituted Pyrimidine Derivatives Containing Urea Moiety, Safety of 2-Chloroacetamide, the publication is Russian Journal of Bioorganic Chemistry (2021), 47(6), 1301-1311, database is CAplus.

Abstract: In order to find efficient new antitumor drugs, a series of novel pyrimidine derivatives containing urea moiety were designed and synthesized, and the antitumor activity of four human tumor cells was evaluated by MTT anal. The results showed that most of the target compounds exhibited moderate antitumor activity. In particular, the IC₅₀ (concentration required to achieve 50% inhibition of the tumor cell proliferation) value of compound 2-((4-(4-ethylphenoxy)-6-(trifluoromethyl)pyrimidin-2-yl)thio)-N-((4-ethylphenyl)carbamoyl)acetamide for MGC-803 (human gastric carcinoma cell line) was 2.51 ± 0.17μmol L^-1, the anti-proliferative activity was significantly better than the pos. control drug 5-fluorouracil. Mol. docking revealed that this compound can bind well to the active site of epidermal growth factor receptor (EGFR), and it may become a potential antitumor drug.

Russian Journal of Bioorganic Chemistry published new progress about 79-07-2. 79-07-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Aliphatic hydrocarbon chain,Amide,Inhibitor, name is 2-Chloroacetamide, and the molecular formula is C2H4ClNO, Safety of 2-Chloroacetamide.

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