Month: November 2022

Turdi, Huji published the artcileScreening Hit to Clinical Candidate: Discovery of BMS-963272, a Potent, Selective MGAT2 Inhibitor for the Treatment of Metabolic Disorders, SDS of cas: 343338-28-3, the main research area is MGAT2 inhibitor metabolic disorder aryl dihydropyridinone.

MGAT2 inhibition is a potential therapeutic approach for the treatment of metabolic disorders. High-throughput screening of the BMS internal compound collection identified the aryl dihydropyridinone compound 1 (hMGAT2 IC50 = 175 nM) as a hit. Compound 1 had moderate potency against human MGAT2, was inactive vs mouse MGAT2 and had poor microsomal metabolic stability. A novel chem. route was developed to synthesize aryl dihydropyridinone analogs to explore structure-activity relationship around this hit, leading to the discovery of potent and selective MGAT2 inhibitors 21f, 21s, and 28e that are stable to liver microsomal metabolism After triaging out 21f due to its inferior in vivo potency, pharmacokinetics, and structure-based liabilities and tetrazole 28e due to its inferior channel liability profile, 21s (BMS-963272) was selected as the clin. candidate following demonstration of on-target weight loss efficacy in the diet-induced obese mouse model and an acceptable safety and tolerability profile in multiple preclin. species.

Journal of Medicinal Chemistry published new progress about Body weight loss. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, SDS of cas: 343338-28-3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Li, Jianwei published the artcileEvaluation of blood simulating solvents in extractables and leachables testing for chemical characterization of medical devices based on Abraham general solvation model, Recommanded Product: N-Methylformamide, the main research area is blood simulating solvents extract chem characterization medical device.

Extraction vehicles (simulating solvents) used in chem. characterization (i.e., extractables/leachables testing) of blood-contacting medical devices for biocompatibility assessment per ISO 10993 have been studied by Abraham general solvation models. Chem. equivalent solvents to blood in solvation properties (solubility, partition, extraction, etc.) have been proposed based on Abraham’s organic solvent system coefficients for water and air to condensed organic solvent phases. This evaluation is built upon the conclusion by Abraham, Acree Jr and Cometto-Munĩz that water saturated n-butanol (called wet n-butanol) is chem. corresponding to blood. Although wet n-butanol can be directly used to replace blood in an extraction study (such as a simulated-use extraction study per ISO 10993-18 (2020)), it can be beneficial to have alternate solvents to wet n-butanol (butan-1-ol) when chromatog. interference is practically significant. By comparing Abraham solvent system coefficients for water to condensed organic solvent phases distribution, a five-dimensional space distance (D) between solvents and reference solvent (wet n-butanol) is calculated using Abraham and Martin equation to predict equivalent or similar solvents (to wet n-butanol). It is concluded from the study that ethanol/water (60/40, V/V) and ethanol/water (50/50, V/V) are chem. equivalent or quite similar to wet n-Butanol. Other two less similar solvents are ethylene glycol and ethanol/water (70/30, V/V). Thus, n-butanol, ethanol/water (60/40, V/V) and ethanol/water (50/50, V/V) can be used as blood simulating solvents in chem. characterization study of medical device. In certain situations, ethylene glycol might be desirable as an alternate solvent, as it is not a mixture As Abraham solvation model is general (solvent system specific, not solute specific), the conclusions from this study are considered as universal.

Journal of Molecular Liquids published new progress about Biocompatibility. 123-39-7 belongs to class amides-buliding-blocks, name is N-Methylformamide, and the molecular formula is C2H5NO, Recommanded Product: N-Methylformamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Moszner, Norbert published the artcileMonomers for adhesive polymers, 4 synthesis and radical polymerization of hydrolytically stable crosslinking monomers, Recommanded Product: N,N’-(Butane-1,4-diyl)diacrylamide, the main research area is dentin adhesive bisacrylamide monomer.

Hydrolytically stable, crosslinking bis(acrylamide)s 1a-1l or bis(methacrylamide)s 2a-2c were synthesized by reaction of acryloyl or methacryloyl chloride using primary or secondary amines. In addition, monomers 3a and 3b were obtained by amidation of 2,6-dimethylene-4-oxaheptane-1,7-dicarboxylic acid (DMOHDA) with propylamine and diethylamine, resp. The structures of the monomers were characterized by IR, 1H, and 13C NMR spectroscopy. All monomers containing N,N’-monosubstituted carbamide groups were solids. Those containing N,N’-disubstituted carbamide groups were water-soluble liquids Water-soluble bis(acrylamide) 1d (N,N’-diethyl-1,3-bis(acrylamido)propane) shows a radical polymerization reactivity in the presence of 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AMPAHC) similar to that of glycerol dimethacrylate, as revealed by gelation experiments in water. 1D is hydrolytically stable in 20 weight-% phosphoric acid and can be used to substitute dimethacrylates in self-etching dentin adhesives. Furthermore, this monomer was also suitable as a reactive diluent in composites.

Macromolecular Materials and Engineering published new progress about Bending strength. 10405-38-6 belongs to class amides-buliding-blocks, name is N,N’-(Butane-1,4-diyl)diacrylamide, and the molecular formula is C10H16N2O2, Recommanded Product: N,N’-(Butane-1,4-diyl)diacrylamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Li, Keng-Yuan published the artcileFluorinated montmorillonite and 3YSZ as the inorganic fillers in fluoride-releasing and rechargeable dental composition resin, Recommanded Product: N-Methylformamide, the main research area is montmorillonite yttria stabilized zirconia filler fluoride dental composition resin; Bis-GMA; bentonite; composite resins; dental caries; fluorides; zirconium.

Dental caries (tooth decay) is the most frequent oral disease in humans. Filling cavities with a dental restorative material is the most common treatment, and glass ionomer cements are the main fluoride ion release restorative materials. The goal of this study was to develop a restorative compound with superior fluoride ion release and recharge abilities. Previously developed fluorinated bentolite and hydrophobized 3YSZ were used as two different inorganic fillers mixed in a bisphenol A-glycidyl methacrylate (Bis-GMA) matrix. XRD, FTIR, and TGA were used to determine the hydrophobic modification of these two inorganic fillers. In mech. tests, including diameter tensile strength, flexural strength, and wear resistance, the developed composite resin was significantly superior to the com. control. A WST-1 assay was used to confirm that the material displayed good biocompatibility. Furthermore, the simulation of the oral environment confirmed that the composite resin had good fluoride ion release and reloading abilities. Thus, the composite resin developed in this study may reduce secondary caries and provide a new choice for future clin. treatments.

Polymers (Basel, Switzerland) published new progress about Bending strength. 123-39-7 belongs to class amides-buliding-blocks, name is N-Methylformamide, and the molecular formula is C2H5NO, Recommanded Product: N-Methylformamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Lee, Kin Long Kelvin published the artcileBayesian Analysis of Theoretical Rotational Constants from Low-Cost Electronic Structure Methods, COA of Formula: C2H5NO, the main research area is Bayesian analysis mol rotational constant electronic structure method.

With an ever-increasing usage of electronic structure programs by the microwave spectroscopy community, there is a growing need to assess the performance of commonly used, low-cost quantum chem. methods, particularly with respect to rotational constants because these quantities are central in guiding experiments Here, we systematically benchmark the predictive power afforded by several low-level ab initio and d. functionals combined with a variety of basis sets that are commonly employed in the rotational spectroscopy literature. The data set in our anal. consists of 6916 optimized geometries of 76 representative species where high-resolution exptl. gas-phase rotational constants are available. We adopted a Bayesian approach for analyzing the performance of each method and basis set combination, employing Hamiltonian Monte Carlo sampling to determine the uncertainty in theor. predictions of rotational constants and dipole moments. Our anal. establishes a hierarchy of accuracy and uncertainty, with commonly used methods in the rotational spectroscopy literature such as B3LYP and MP2 yielding lower accuracy and higher uncertainty than newer-generation functionals such as those from the Minnesota family, and ωB97X-D, which, when paired with a modestly sized 6-31+G(d) basis, provides optimal performance with respect to computational cost. Addnl., we provide statistical scaling factors that can be used to empirically correct for vibration-rotation effects, as a means to further improve the accuracy of rotational constants predicted from these relatively low-cost theor. methods. As part of this, we demonstrate that the uncertainties can be used in simulations of rotational spectra to cross-correlate with broadband spectra, a methodol. that could be used to quickly and efficiently survey exptl. spectra for new mols.

Journal of Physical Chemistry A published new progress about Bayesian network. 123-39-7 belongs to class amides-buliding-blocks, name is N-Methylformamide, and the molecular formula is C2H5NO, COA of Formula: C2H5NO.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Lin, Yiyang published the artcileResidue-Specific Solvation-Directed Thermodynamic and Kinetic Control over Peptide Self-Assembly with 1D/2D Structure Selection, Synthetic Route of 123-39-7, the main research area is peptide self assembly solvation thermodn kinetics trapping cosolvent; 2D structures; fibrils; pathway dependence; peptide solvation; self-assembly.

Understanding the self-organization and structural transformations of mol. ensembles is important to explore the complexity of biol. systems. Here, we illustrate the crucial role of cosolvents and solvation effects in thermodn. and kinetic control over peptide association into ultrathin Janus nanosheets, elongated nanobelts, and amyloid-like fibrils. We gained further insight into the solvation-directed self-assembly (SDSA) by investigating residue-specific peptide solvation using mol. dynamics modeling. We proposed the preferential solvation of the aromatic and alkyl domains on the peptide backbone and protofibril surface, which results in volume exclusion effects and restricts the peptide association between hydrophobic walls. We explored the SDSA phenomenon in a library of cosolvents (protic and aprotic), where less polar cosolvents were found to exert a stronger influence on the energetic balance at play during peptide propagation. By tailoring cosolvent polarity, we were able to achieve precise control of the peptide nanostructures with 1D/2D shape selection. We also illustrated the complexity of the SDSA system with pathway-dependent peptide aggregation, where two self-assembly states (i.e., thermodn. equilibrium state and kinetically trapped state) from different sample preparation methods were obtained.

ACS Nano published new progress about Aprotic solvents. 123-39-7 belongs to class amides-buliding-blocks, name is N-Methylformamide, and the molecular formula is C2H5NO, Synthetic Route of 123-39-7.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Yu, Yingmin published the artcileEntrainers Selection and Vapor-Liquid Equilibrium Measurements for Separation of p-Xylene from Ethylbenzene at 101.3 kPa, Product Details of C2H5NO, the main research area is para xylene ethylbenzene trichlorobenzene vapor liquid equilibrium thermodn simulation.

In this paper, the separation of the p-xylene and ethylbenzene was explored. The COSMO-SAC-UNIFAC model, σ-profile anal., solvent power and selectivity were used to screen for a suitable solvent for this process. Then, 1,2,4-trichlorobenzene was selected as target solvent to extract the p-xylene from ethylbenzene. The vapor-liquid-phase equilibrium (VLE) data for binary systems of p-xylene + ethylbenzene, p-xylene + 1,2,4-trichlorobenzene, and ethylbenzene + 1,2,4-trichlorobenzene and ternary system of p-xylene + ethylbenzene + 1,2,4-trichlorobenzene were determined with a modified Rose still at atm. pressure (101.3 kPa) and all the binary data passed the Wisniak’s test, which accorded with the thermodn. consistency. Three thermodn. models, Wilson, NRTL and UNIQUAC were used to correlate the VLE data and get binary interaction parameters, then the ternary VLE data of p-xylene + ethylbenzene + 1,2,4-trichlorobenzene were estimated based on these model parameters using Aspen Plus V10. The estimation values of the three models are in good agreement with the exptl. data. Moreover, the effect of 1,2,4-trichlorobenzene was analyzed and it was found to be an effective candidate extractant for the extractive distillation of ethylbenzene from mixed xylenes.

Journal of Solution Chemistry published new progress about Antoine equation. 123-39-7 belongs to class amides-buliding-blocks, name is N-Methylformamide, and the molecular formula is C2H5NO, Product Details of C2H5NO.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Popelier, P. L. A. published the artcileQSAR models based on quantum topological molecular similarity, Recommanded Product: 2,2-Difluoroacetamide, the main research area is QSAR model quantum topol similarity.

A new method called quantum topol. mol. similarity (QTMS) was fairly recently proposed [J. Chem. Inf. Comp. Sc., 41, 2001, 764] to construct a variety of medicinal, ecol. and phys. organic QSAR/QSPRs. QTMS method uses quantum chem. topol. (QCT) to define electronic descriptors drawn from modern ab initio wave functions of geometry-optimized mols. It was shown that the current abundance of computing power can be utilized to inject realistic descriptors into QSAR/QSPRs. In this article the authors study seven datasets of medicinal interest: the dissociation constants (pKa) for a set of substituted imidazolines, the pKa of imidazoles, the ability of a set of indole derivatives to displace [3H] flunitrazepam from binding to bovine cortical membranes, the influenza inhibition constants for a set of benzimidazoles, the interaction constants for a set of amides and the enzyme liver alc. dehydrogenase, the natriuretic activity of sulfonamide carbonic anhydrase inhibitors and the toxicity of a series of benzyl alcs. A partial least square anal. in conjunction with a genetic algorithm delivered excellent models. They are also able to highlight the active site, of the ligand or the mol. whose structure determines the activity. The advantages and limitations of QTMS are discussed.

European Journal of Medicinal Chemistry published new progress about Antiviral agents. 359-38-6 belongs to class amides-buliding-blocks, name is 2,2-Difluoroacetamide, and the molecular formula is C2H3F2NO, Recommanded Product: 2,2-Difluoroacetamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Mayhoub, Abdelrahman S. published the artcileAn investigation of phenylthiazole antiflaviviral agents, COA of Formula: C11H15NS, the main research area is antiflaviviral phenylthiazole preparation SAR.

Flaviviruses are one of the most clin. important pathogens and their infection rates are increasing steadily. The phenylthiazole ring system has provided a template for the design and synthesis of antiviral agents that inhibit the flaviviruses by targeting their E-protein. Unfortunately, there is a correlation between phenylthiazole antiflaviviral activity and the presence of the reactive and therefore potentially toxic mono- or dibromomethyl moieties at thiazole-C4. Adding a linear hydrophobic tail para to the Ph ring led to a new class of phenylthiazole antiflaviviral compounds that lack the toxic dibromomethyl moiety. This led to development of a drug-like phenylthiazole 12 (I) that had high antiflaviviral selectivity (TI = 147).

Bioorganic & Medicinal Chemistry published new progress about Antiviral agents. 1208077-46-6 belongs to class amides-buliding-blocks, name is 4-Butylthiobenzamide, and the molecular formula is C11H15NS, COA of Formula: C11H15NS.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Link, John O. published the artcileClinical targeting of HIV capsid protein with a long-acting small molecule, COA of Formula: C4H11NOS, the main research area is HIV infection capsid protein antiviral GS6207 viral replication cycle.

Abstract: Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1-5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can neg. affect the outcome of treatment-which contributes to virol. failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7-9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and addnl. can improve adherence10. Here we describe GS-6207, a small mol. that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the s.c. injection site. Drawing on X-ray crystallog. information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clin. studies, monotherapy with a single s.c. dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 mo. These results provide clin. validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV.

Nature (London, United Kingdom) published new progress about Antiviral agents. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, COA of Formula: C4H11NOS.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics