Month: November 2022

Fang, Tianan published the artcileOrally bioavailable amine-linked macrocyclic inhibitors of factor XIa, SDS of cas: 343338-28-3, the main research area is preparation oral amine linked macrocyclic factor XIa inhibitor anticoagulant; Activated partial thromboplastin time; FXIa; Factor Xia; Thrombosis; aPTT.

The discovery of orally bioavailable FXIa inhibitors has been a challenge. Herein, we describe our efforts to address this challenge by optimization of our imidazole-based macrocyclic series. Our optimization strategy focused on modifications to the P2 prime, macrocyclic amide linker, and the imidazole scaffold. Replacing the amide of the macrocyclic linker with amide isosteres led to the discovery of substituted amine linkers which not only maintained FXIa binding affinity but also improved oral exposure in rats. Combining the optimized macrocyclic amine linker with a pyridine scaffold afforded compounds 23 and 24 that were orally bioavailable, single-digit nanomolar FXIa inhibitors with excellent selectivity against relevant blood coagulation enzymes.

Bioorganic & Medicinal Chemistry Letters published new progress about Anticoagulants. 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

Corte, James R. published the artcilePotent, Orally Bioavailable, and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups, HPLC of Formula: 343338-28-3, the main research area is thrombosis FXIa inhibitors orally bioavailable blood coagulation enzymes.

Factor XIa (FXIa) inhibitors are promising novel anticoagulants, which show excellent efficacy in preclin. thrombosis models with minimal effects on hemostasis. The discovery of potent and selective FXIa inhibitors which are also orally bioavailable has been a challenge. Here, we describe optimization of the imidazole-based macrocyclic series and our initial progress toward meeting this challenge. A two-pronged strategy, which focused on replacement of the imidazole scaffold and the design of new P1 groups, led to the discovery of potent, orally bioavailable pyridine-based macrocyclic FXIa inhibitors. Moreover, pyridine-based macrocycle 19, possessing the phenylimidazole carboxamide P1, exhibited excellent selectivity against relevant blood coagulation enzymes and displayed antithrombotic efficacy in a rabbit thrombosis model.

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

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

Okuma, Rika published the artcileA macrocyclic peptide library with a structurally constrained cyclopropane-containing building block leads to thiol-independent inhibitors of phosphoglycerate mutase, COA of Formula: C4H11NOS, the main research area is peptide cyclopropane macrocycle library thioether synthesis mRNA encoded; cyclopropane amino acid synthesis peptide cyclization anthelmintic agent filarial; anthelmintic drug target phosphoglycerate mutase enzyme inhibiting structure activity; DNA library sequence mutagenesis genetic code reprogramming SPR; cyclopropane; genetic code reprogramming; mRNA display; macrocyclic peptide.

Here we report the construction of an mRNA-encoded library of thioether-closed macrocyclic peptides by using an N-chloroacetyl-cyclopropane-containing exotic initiator whose structure is more constrained than the ordinary N-chloroacetyl-α-amino acid initiators. The use of such an initiator has led to a macrocycle library with significantly suppressed population of lariat-shaped species compared with the conventional libraries. We previously used a conventional library and identified a small lariat thioether-macrocycle with a tail peptide with a C-terminal free Cys whose side-chain plays an essential role in potent inhibitory activity against a parasitic model enzyme, phosphoglycerate mutase. On the other hand, the cyclopropane-containing macrocycle library has yielded a larger thioether-macrocycle lacking a free Cys residue, which exhibits potent inhibitory activity to the same enzyme with a different mode of action. This result indicates that such a cyclopropane-containing macrocycle library would allow us to access mechanistically distinct macrocycles.

Chemistry – An Asian Journal published new progress about Aminoacylation. 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

Hansch, Corwin published the artcileA quantitative structure-activity relationship and molecular graphics analysis of hydrophobic effects in the interactions of inhibitors with alcohol dehydrogenase, Formula: C2H3F2NO, the main research area is alc dehydrogenase inhibitor QSAR; liver alc dehydrogenase inhibitor QSAR; structure activity alc dehydrogenase inhibitor.

An anal. of the Ki values of pyrazoles, phenylacetamides, formylbenzylamines, and acetamides acting on liver alc. dehydrogenase (ADH) yielded quant. structure-activity relations (QSAR) having a linear dependency on octanol-water partition coefficients (P). The average coefficient and standard deviation with the log P term for 6 different QSARs was 0.96. This suggested complete desolvation of the substituents (directly comparable to partitioning into octanol) on binding to the enzyme. A study of a mol. graphics model of ADH constructed from x-ray crystallog. coordinates showed that the substituents are engulfed in a long hydrophobic channel which is so narrow that water of solvation must be removed from them in the binding process.

Journal of Medicinal Chemistry published new progress about Enzyme kinetics. 359-38-6 belongs to class amides-buliding-blocks, name is 2,2-Difluoroacetamide, and the molecular formula is C2H3F2NO, Formula: C2H3F2NO.

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

McCarville, Michael published the artcilePhosphorescent probes for proteins, Quality Control of 35203-88-4, the main research area is carbonic anhydrase inhibitor phosphorescent; tryptophan energy transfer; protein phosphorescent probes.

Use of bound phosphorescent chromophores to study protein structure was investigated. Carbonic anhydrase inhibitors with 3 different arrangements of singlet and triplet energy levels relative to those of tryptophan were used to determine their ability to transfer triplet energy. Ligands representing each of the 3 energy level arrangements were found to exhibit triplet-triplet energy transfer with a tryptophan residue at the active site of carbonic anhydrase. This greatly increases the number of ligands which may be useful as phosphorescent probes and is a potential source of data for determining the position of the ligand in the binding site.

Biochimica et Biophysica Acta, Protein Structure published new progress about Energy transfer. 35203-88-4 belongs to class amides-buliding-blocks, name is 3-Acetylbenzenesulfonamide, and the molecular formula is C8H9NO3S, Quality Control of 35203-88-4.

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

Galley, W. C. published the artcileKinetics of triplet-triplet energy transfer and intramolecular distances in enzyme-inhibitor complexes, Formula: C8H9NO3S, the main research area is kinetics energy transfer bimol; enzyme inhibitor complex conformation; mol distance energy transfer.

The kinetics of triplet-triplet energy transfer and donor-acceptor geometries were used to estimate mol. distances in bimol. systems and to measure variability within enzyme-inhibitor complexes. The average distance from the center of the energy donor (m-acetylbenzene sulfonamide) to that of ≥1 tryptophan residue in bovine, human B, and human C forms of carbonic anhydrase were estimated as 10.1, <9.5, and 10.4 Å, resp. The use of kinetics of triplet energy transfer is recommended for studying bimol. conformations. Nature (London, United Kingdom) published new progress about Energy transfer. 35203-88-4 belongs to class amides-buliding-blocks, name is 3-Acetylbenzenesulfonamide, and the molecular formula is C8H9NO3S, Formula: C8H9NO3S.

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

Lu, Nan published the artcileNon-aqueous electrophoresis integrated with electrospray ionization mass spectrometry on a thiol-ene polymer-based microchip device, Synthetic Route of 123-39-7, the main research area is electrophoresis integrated electrospray ionization mass spectrometry thiol ene polymer; microchip device; Electrospray interface; Microfluidics; Non-aqueous electrophoresis; Thiol-ene polymers.

Abstract: Non-aqueous capillary electrophoresis (NACE) on microfluidic chips is still a comparatively little explored area, despite the inherent advantages of this technique and its application potential for, in particular, lipophilic compounds A main reason is probably the fact that implementation of NACE on microchips largely precluded the use of polymeric substrate materials. Here, we report non-aqueous electrophoresis on a thiol-ene-based microfluidic chip coupled to mass spectrometry via an on-chip ESI interface. Microchips with an integrated ESI emitter were fabricated using a double-molding approach. The durability of thiol-ene, when exposed to different organic solvents, was investigated with respect to swelling and decomposition of the polymer. Thiol-ene exhibited good stability against organic solvents such as methanol, ethanol, N-methylformamide, and formamide, which allows for a wide range of background electrolyte compositions The integrated ESI emitter provided a stable spray with RSD% of the ESI signal ≤8%. Separation efficiency of the developed microchip electrophoresis system in different non-aqueous buffer solutions was tested with a mixture of several drugs of abuse. Ethanol- and methanol-based buffers provided comparable high theor. plate numbers (≈ 6.6 x 104-1.6 x 105 m-1) with ethanol exhibiting the best separation efficiency. Direct coupling of non-aqueous electrophoresis to mass spectrometry allowed for fast anal. of hydrophobic compounds in the range of 0.1-5μg mL-1 and 0.2-10μg mL-1 and very good sensitivities (LOD ≈ 0.06-0.28μg mL-1; LOQ ≈ 0.20-0.90μg mL-1). The novel combination of non-aqueous CE on a microfluidic thiol-ene device and ESI-MS provides a mass-producible and highly versatile system for the anal. of, in particular, lipophilic compounds in a wide range of organic solvents. This offers promising potential for future applications in forensic, clin., and environmental anal.

Analytical and Bioanalytical Chemistry published new progress about Electrophoresis. 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

Hayat, Waseem published the artcileInsight into the degradation of methomyl in water by peroxymonosulfate, Application In Synthesis of 123-39-7, the main research area is methomyl peroxymonosulfate oxidative wastewater treatment.

Methomyl (MET) is a carbamate pesticide frequently used in agriculture, globally. Its high solubility makes it a potential water pollutant. MET can be removed by peroxymonosulfate (PMS)-based advanced oxidation processes. This study explains MET degradation by PMS-Only, pyrite (PyR)-PMS and zero-valent iron (ZVI)-PMS systems. The degradation by PMS-Only, PyR-PMS and ZVI-PMS systems was 85.4%, 94.9% and 87.0%, resp. The generation of reactive oxygen species (ROS) and their role in degradation was elucidated by ESR (EPR) and free-radical quenching analyses, resp. EPR anal. indicated the presence of sulfate (SO•-4) and hydroxyl (•OH) radicals. The degradation in PMS-Only and ZVI-PMS systems was not significantly inhibited by tert-Bu alc. (TBA) and methanol (MeOH), which suggests that the degradation in both systems was not majorly carried out by SO•-4 and •OH. However, furfuryl acid (FFA) resulted in reduced degradation by applied systems, which showed that singlet oxygen (1O2) was mainly responsible for degradation in all systems. These results showed that MET was majorly degraded by non-radical PMS oxidation PMS-Only system resulted in an almost equal degradation, compared with PyR-PMS and ZVI-PMS systems. So, detailed anal. was carried out for PMS-Only system. Hence, experiments were conducted to investigate the effect of PMS concentration, MET concentration, pH and temperature on the degradation by PMS-Only system, which showed that PMS-Only system was efficient from pH 5.0 to pH 9.0, and from 10.0 °C to 40.0 °C. Further, PMS-Only system has a potential for effective degradation in real waters because it resulted in 66.5%, 63.7% and 60.4% degradation in tap water, lake water and sewage water, resp.

Journal of Environmental Chemical Engineering published new progress about Drinking waters. 123-39-7 belongs to class amides-buliding-blocks, name is N-Methylformamide, and the molecular formula is C2H5NO, Application In Synthesis of 123-39-7.

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

Jacobs, Jeffrey W. published the artcileDiscovery of Tenapanor: A First-in-Class Minimally Systemic Inhibitor of Intestinal Na+/H+ Exchanger Isoform 3, SDS of cas: 35203-88-4, the main research area is tenapanor inhibitor intestine sodium hydrogen exchanger isoform 3 NHE3.

We present herein the design, synthesis, and optimization of gut-restricted inhibitors of Na+/H+ exchanger isoform 3 (NHE3). NHE3 is predominantly expressed in the kidney and gastrointestinal tract where it acts as the major absorptive sodium transporter. We desired minimally systemic agents that would block sodium absorption in the gastrointestinal tract but avoid exposure in the kidney. Starting with a relatively low-potency highly bioavailable hit compound (1), potent and minimally absorbed NHE3 inhibitors were designed, culminating with the discovery of tenapanor (28). Tenapanor has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of irritable bowel syndrome with constipation in adults.

ACS Medicinal Chemistry Letters published new progress about Digestive tract. 35203-88-4 belongs to class amides-buliding-blocks, name is 3-Acetylbenzenesulfonamide, and the molecular formula is C8H9NO3S, SDS of cas: 35203-88-4.

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

Machida, Shingo published the artcileA novel approach to characterization of a relatively unstable intercalation compound under ambient conditions: revisiting a kaolinite-acetone intercalation compound, Name: N-Methylformamide, the main research area is kaolinite acetone intercalation hydrogen bond.

Characteristics of a kaolinite-acetone intercalation compound prepared using a kaolinite N-methylformamide intercalation compound (Kaol-NMF) as an intermediate were obtained by a set of techniques with attention to suppressing evaporation and deintercalation of acetone. X-ray diffraction (XRD) with spectroscopic analyses, Fourier-transform IR spectroscopy (FTIR) accompanied by solid-state 13C and 29Si NMR (NMR) spectroscopy with cross polarization (CP) and magic angle spinning (MAS) enable us to demonstrate full replacement of a pre-intercalated NMF monolayer with an acetone monolayer between the layers of kaolinite with an increase in the basal spacing from 1.08 nm (Kaol-NMF) to 1.12 nm. In addition, the appearance of an addnl. OH stretching band at 3630 cm-1 and the shift of the C=O stretching band to a lower wavenumber, from 1714 to 1701 cm-1, in the FTIR spectrum, along with a downfield shift of the signal due to C=O groups from 209 ppm, where a singlet was observed in the liquid-state 13C NMR spectrum of acetone in CDCl3, to 219 ppm in the 13C CP/MAS NMR spectrum, indicate hydrogen bond formation between interlayer hydroxyl groups of kaolinite and C=O groups of the intercalated acetone mols. These careful characterization studies provide information on an interaction between kaolinite and acetone under ambient conditions.

Dalton Transactions published new progress about Deintercalation. 123-39-7 belongs to class amides-buliding-blocks, name is N-Methylformamide, and the molecular formula is C2H5NO, Name: N-Methylformamide.

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