Day: December 6, 2022

Liu, Bei-Bei published the artcileNS8593 inhibits Ca2+ permeant channels reversing mouse airway smooth muscle contraction, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is NS8593 calcium channel airway smooth muscle allergic asthma; Airway smooth muscle; L-type voltage-dependent Ca(2+) channel; NS8593; Store-operated Ca(2+) entry; Transient receptor potential channel.

This study focused on investigating whether NS8593 reverses airway smooth muscle (ASM) contraction and the underlying mechanism. ASM contraction in mouse tracheal rings and lung slices was measured. Currents mediated by voltage dependent Ca2+ channels (VDCCs) and ACH-activated channels were measured using the whole-cell patch-clamp technique in single tracheal smooth muscle cells (TSMCs). Intracellular Ca2+ level and cell length were measured using an LSM 700 laser confocal microscope and a Zen 2010 software. Mouse respiratory system resistance (Rrs) was assessed using a FlexiVent FX system. High K+ (80 mM K+) and ACH induced ASM contraction in mouse tracheal rings and lung slices, which was partially relaxed by nifedipine (blocker of L-type VDCCs, LVDCCs), YM-58483 (blocker of store-operated Ca2+ entry (SOCE), transient receptor potential C3 (TRPC3) and TRPC5 channels), resp. However, the contraction was completely reversed by NS8593, whereas, slightly relaxed by formoterol. ACH activated inward currents, which displayed linear and reversed around 0 mV, indicating the currents were mediated by non-selective cation channels (NSCCs). Moreover, these currents were blocked by YM-58483. In addition, such currents were abolished by NS8593, implicating that NS8593 inhibits the same channels. Besides, NS8593 inhibited increases of intracellular Ca2+ and the associated cell shortening. Finally, NS8593 inhibited ACH-induced increases of mouse respirator system resistance (Rrs). Our results indicate that NS8593 inhibits LVDCCs and NSCCs, resulting in decreases of intracellular Ca2+ and then leading to ASM relaxation. These data suggest that NS8593 might be a new bronchodilator.

Life Sciences published new progress about Allergic asthma. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Perry, Matthew W. D. published the artcileDiscovery of AZD8154, a Dual PI3Kγδ Inhibitor for the Treatment of Asthma, Related Products of pyridine-derivatives, the main research area is AZD8154 PI3K gamma delta inhibitor asthma inhaled.

Starting from our previously described PI3Kγ inhibitors, we describe the exploration of structure-activity relationships that led to the discovery of highly potent dual PI3Kγδ inhibitors. We explored changes in two positions of the mols., including macrocyclization, but ultimately identified a simpler series with the desired potency profile that had suitable physicochem. properties for inhalation. We were able to demonstrate efficacy in a rat ovalbumin challenge model of allergic asthma and in cells derived from asthmatic patients. The optimized compound, AZD8154, has a long duration of action in the lung and low systemic exposure coupled with high selectivity against off-targets.

Journal of Medicinal Chemistry published new progress about Allergic asthma. 21190-89-6 belongs to class pyridine-derivatives, name is Ethyl 6-chloropicolinate, and the molecular formula is C8H8ClNO2, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Guiping published the artcileDiscovery of N-substituted (2-phenylcyclopropyl)methylamines as functionally selective serotonin 2C receptor agonists for potential use as antipsychotic medications, Application In Synthesis of 71255-09-9, the main research area is phenylcyclopropylmethylamine preparation serotonin 2C receptor agonist antipsychotic.

A series of N-substituted (2-phenylcyclopropyl)methylamines were designed and synthesized, with the aim of finding serotonin 2C (5-HT2C)-selective agonists with a preference for Gq signaling. A number of these compounds exhibit 5-HT2C selectivity with a preference for Gq-mediated signaling compared with β-arrestin recruitment. Furthermore, the N-Me compound I•HCl, which displayed an EC50 of 23 nM in the calcium flux assay while showing no β-arrestin recruitment activity, is the most functionally selective 5-HT2C agonist reported to date. The N-benzyl compound II•HCl, which showed an EC50 of 24 nM at the 5-HT2C receptor, is fully selective over the 5-HT2B receptor. In an amphetamine-induced hyperactivity model, compound II showed significant antipsychotic-drug-like activity. These compounds shed light on the role of functional selectivity at the 5-HT2C receptor with respect to antipsychotic activity.

Journal of Medicinal Chemistry published new progress about 5-HT2C agonists. 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Application In Synthesis of 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hansen, Martin published the artcileSynthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines as 5-HT2A/2C partial agonists, Computed Properties of 71255-09-9, the main research area is bromodimethoxy phenethyl amine preparation 5HT2A 5HT2C agonist; 5-HT(2A) agonists; N-Benzyl phenethylamines; Selectivity; Serotonin; Structure activity relations.

N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives Special attention is given to the 2′ and 3′-position of the N-benzyl as such compounds are known to be very potent. We found that substitutions in these positions are generally well tolerated. The 2′-position was further examined using a range of substituents to probe the hydrogen bonding requirements for optimal affinity and selectivity, and it was found that small changes in the ligands in this area had a profound effect on their affinities. Furthermore, two ligands that lack a 2′-benzyl substituent were also found to have high affinity contradicting previous held notions. Several high-affinity ligands were identified and assayed for functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines.

Bioorganic & Medicinal Chemistry published new progress about 5-HT2A agonists. 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Computed Properties of 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Odani, Noritaka published the artcileDetermining the effect of photodegradation on film coated nifedipine tablets with terahertz based coating thickness measurements, Related Products of pyridine-derivatives, the main research area is nifedipine film coating thickness photodegradation TOF MLR; Photostability; Process analytical technology; Tablet coating; Terahertz spectroscopy.

Film coating of nifedipine tablets is commonly performed to reduce photo-degradation The coating thickness of these tablets is a primary dictating factor of photo-stability. Terahertz spectroscopy enables accurate measurement of coating thickness. This study identifies a method to determine an end-point of a photo-protective coating process by using coating thickness measurements from terahertz time of flight spectroscopy (THz-TOF). For this method, nifedipine tablets, at different coating thicknesses, were placed in a photostability chamber. The illumination conditions of the coated tablets were adjusted based on the time duration of these tablets inside the chamber. A multiple linear regression model was developed with the coating thickness estimates from THz-TOF and illumination conditions information to predict the amount of drug remaining after photo-degradation (percent label claim). The prediction error of this model was 1.03% label claim in the range of 88.4-100.6% label claim. According to this model, acceptable levels of photo-protection in illumination conditions of up to approx. 700,000 lx hours was achieved at the end of the coating process (approx. 50 ^fmm coating thickness) performed in this study. These results suggest THz-TOF as a viable process anal. technol. tool for process understanding and end-point determination of a photo-protective coating process.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Far-IR radiation. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ghiazza, Clement published the artcileDeaminative chlorination of aminoheterocycles, HPLC of Formula: 24484-93-3, the main research area is chloro heterocycle selective preparation; aminoheterocycle deaminative chlorination.

Herein we present a simple methodol. that enabled the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)-NH2 could be converted into C(sp2)-Cl bonds. The method was characterized by its wide functional group tolerance and substrate scope, allowing the modification of different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH2 into Cl in a late-stage fashion enabled practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents.

Nature Chemistry published new progress about Chemoselectivity. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, HPLC of Formula: 24484-93-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Spencer, John published the artcileSynthesis and solid state study of pyridine- and pyrimidine-based fragment libraries, Quality Control of 26820-62-2, the main research area is preparation pyridine pyrimidine library solid state study microwave irradiation.

A library of pyridines and pyrimidines, e.g. I [X = CH, N], has been synthesized in excellent yields employing microwave and flow chem. methodologies. Work-up bottlenecks have been facilitated substantially by the use of supported reagents and many of the final compounds have been studied in the solid state by single crystal X-ray diffraction.

Tetrahedron Letters published new progress about Chemical library. 26820-62-2 belongs to class pyridine-derivatives, name is 4-(5-Nitropyridin-2-yl)morpholine, and the molecular formula is C9H11N3O3, Quality Control of 26820-62-2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yang, Min published the artcilePalladium-Catalyzed C-4 Selective Coupling of 2,4-Dichloropyridines and Synthesis of Pyridine-Based Dyes for Live-Cell Imaging, Application In Synthesis of 132097-09-7, the main research area is palladium catalyst coupling dichloropyridine boronic ester toxicity cell imaging; pyridine dye palladium catalyst coupling dichloropyridine boronic ester.

An alternative process of Pd-catalyzed C-4 selective coupling of 2,4-dichloropyridines with boronic esters was developed, which afforded 24 examples of C-4 coupled pyridines in moderate to good yields. After further arylation, 21 examples of C-2, C-4 diarylated pyridines with a significant photophys. property were obtained, which were applied as pyridine-based dyes into live-cell imaging with good biocompatibility and low toxicity.

Journal of Organic Chemistry published new progress about Biocompatibility. 132097-09-7 belongs to class pyridine-derivatives, name is 2,4-Dichloro-3-methylpyridine, and the molecular formula is C6H5Cl2N, Application In Synthesis of 132097-09-7.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Bordallo, Eduardo published the artcileDissolution of amorphous nifedipine from micelle-forming carboxymethylcellulose derivatives, Quality Control of 21829-25-4, the main research area is self assembly amphiphilic polyethylene glycol graft oxidized CM cellulose; micelle CMC graft polyoxyethylene dodecylamine terminated nifedipine; Amphiphilic graft copolymers; Encapsulation; Lipophilic drug; Micelles; Nifedipine; Photostabilization.

We show that a novel amphiphilic graft copolymer combining the biodegradability and biocompatibility of oxidized CM-cellulose (CMC) with that of hydrophilic poly(ethylene glycol) (PEG), and hydrophobic dodecylamine (DDA), improves the solubility and dissolution performance of nifedipine (NIF), considered as a model hydrophobic drug. The hydrophobic components of the graft copolymer have the multiple effect of favoring micelle formation and loading. At the same time, the interaction between the hydrophobic core and NIF has the secondary effect to suppress drug crystallization, favoring its dissolution, and to increase photostability. Oxidized CMC-g-PEG-DDA micelles reached values of drug concentration, loading capacity and encapsulation efficiency as high as 340μg mL-1, 6.4% and 34.1%, resp. Loaded micelles showed a good stability with a limited release profile at pH 1.2, whereas at pH 7.4 the swollen cores enable much higher and progressive release, that reaches 3.4 and 6.6% after 3 and 5 h, resp., corresponding to very competitive concentration of 34 and 66μg mL-1. A series of oxidized CM-cellulose-graft-poly(ethylene glycol)-dodecylamine (OCMC-g-PEG-DDA) was prepared by using an appositely prepared PEG with terminal amino groups and different amounts of DDA. The nanoaggregates formed in aqueous solution were characterized by surface tension measurements, fluorescence spectroscopy, dynamic light scattering (DLS) and scanning electron microscopies (SEM and TEM). The micelles showed narrow hydrodynamic size distributions and diameters varying from 163 to 193 nm depending on the ratio of DDA to PEG chains. The DDA content in the graft copolymers also affected the core-shell interfacial compactness.

Carbohydrate Polymers published new progress about Biocompatibility. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Quality Control of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Radix, Sylvie published the artcileA Journey through Hemetsberger-Knittel, Leimgruber-Batcho and Bartoli Reactions: Access to Several Hydroxy 5- and 6-Azaindoles, Application In Synthesis of 71255-09-9, the main research area is azaindole preparation Hemetsberger Knittel Bartoli Leimgruber Batcho reaction.

The preparation of various 5- and 6-azaindoles, heterocyclic structures e.g., I that are frequently part of mols. in clin. development, and their monohydroxy analogs were described. Different strategies, relying on the de novo pyrrole ring formation, were investigated and, Hemetsberger-Knittel, Bartoli and Leimgruber-Batcho approaches, 4- and 7-monohydroxy 5- and 6-azaindoles e.g., I were obtained. The crucial introduction of the oxygen atom was carried out from halogen derivatives, using nucleophilic substitution reactions under basic conditions with or without a copper catalyst. Some preliminary oxidation reactions have shown that it was yet not possible to synthesize the azaquinone indole structure from monohydroxy azaindole, using mol. oxygen in the presence of salcomine as a catalyst.

Helvetica Chimica Acta published new progress about Bartoli reaction. 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Application In Synthesis of 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem