Month: November 2022

Ogasawara, Daisuke published the artcileDiscovery and Optimization of Selective and in Vivo Active Inhibitors of the Lysophosphatidylserine Lipase α/β-Hydrolase Domain-Containing 12 (ABHD12), Product Details of C6H5Cl2N, the main research area is lysophosphatidylserine lipase hydrolase domain 12 ABHD12 inhibitor.

ABHD12 is a membrane-bound hydrolytic enzyme that acts on the lysophosphatidylserine (lyso-PS) and lysophosphatidylinositol (lyso-PI) classes of immunomodulatory lipids. Human and mouse genetic studies point to a key role for the ABHD12-(lyso)-PS/PI pathway in regulating (neuro)immunol. functions in both the central nervous system and periphery. Selective inhibitors of ABHD12 would offer valuable pharmacol. probes to complement genetic models of ABHD12-regulated (lyso)-PS/PI metabolism and signaling. Here, we provide a detailed description of the discovery and activity-based protein profiling (ABPP) guided optimization of reversible thiourea inhibitors of ABHD12 that culminated in the identification of DO264 as a potent, selective, and in vivo active ABHD12 inhibitor. We also show that DO264, but not a structurally related inactive control probe (S)-DO271, augments inflammatory cytokine production from human THP-1 macrophage cells. The in vitro and in vivo properties of DO264 designate this compound as a suitable chem. probe for studying the biol. functions of ABHD12-(lyso)-PS/PI pathways.

Journal of Medicinal Chemistry published new progress about Crystal structure. 132097-09-7 belongs to class pyridine-derivatives, name is 2,4-Dichloro-3-methylpyridine, and the molecular formula is C6H5Cl2N, Product Details of C6H5Cl2N.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hofbauer, Matthias published the artcileIon-pair charge-transfer complexes of a dithiooxalate zinc donor component with viologens. Synthesis, structural and electronic characterization, Related Products of pyridine-derivatives, the main research area is zincate dithiolato bipyridinium phenanthrolinium pyridylketone preparation; charge transfer zincate dithiolato viologen derivative; electrochem zincate dithiolato viologen derivative; crystal structure zincate dithiolato viologen derivative.

Bipyridinium and phenanthrolinium acceptors of different reduction potentials form with Zn 1,2-dithiooxalates (dto) ion-pair charge-transfer complexes {A2+[Zn(dto)2]2-}. The contact ion pairs exhibit absorptions in the range 390-490 nm which can be attributed to the ion-pair charge-transfer (IPCT) type. On the base of spectroscopic, electrochem. and quantum-chem. studies the relation between optical and thermal electron transfer within the ion pair applying the Hush theory is discussed. The mean reorganization energy of 12 complexes is 180 kJ mol-1 and exceeds the values found for the dithiolene systems. Due to the diminished donor ability of the dithiooxalate unit, a hypsochromic shift of the position of the IPCT band, compared with the metal dithiolenes, results. The extent of electron delocalization from [Zn(dto)2]2- to PQ2+, as described by the parameter α2, is calculated as 4.1 × 10-6. X-ray analyses of BQ[Zn(dto)2] and DP[Zn(dto)2] reveal that the solid-state structure is largely determined by the geometry of the acceptor component.

Inorganica Chimica Acta published new progress about Crystal structure. 36437-30-6 belongs to class pyridine-derivatives, name is 1,1-Di-n-octyl-4,4-bipyridinium Dibromide, and the molecular formula is C26H42Br2N2, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kucharska, E. published the artcileMolecular and crystal structure, IR and Raman spectra, and quantum chemical calculations for 2-hydroxy-3-cyano-4-methylpyridine, Recommanded Product: 2-Chloro-4-methylpyridin-3-amine, the main research area is hydroxycyanomethylpyridine crystallog mol structure IR Raman spectroscopy.

The paper presents the mol. and XRD structures as well as room temperature IR and Raman studies of 2-hydroxy-3-cyano-4-methylpyridine. The nature and assignment of the vibrational modes have been discussed on the basis of the quantum chem. calculations performed with the use of B3LYP/6-311G(d,p) basis set. The role of the hydrogen bonds in the stabilization of the structure has been analyzed. The quantum chem. calculations have been performed for the monomer as well as for the dimer coupled via the hydrogen bonds. A possible application of this compound in the hybrid formation technol. is discussed.

Vibrational Spectroscopy published new progress about Crystal structure. 133627-45-9 belongs to class pyridine-derivatives, name is 2-Chloro-4-methylpyridin-3-amine, and the molecular formula is C6H7ClN2, Recommanded Product: 2-Chloro-4-methylpyridin-3-amine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Hongwei published the artcileThe preparation of felodipine/zein amorphous solid dispersions and in vitro evaluation using a dynamic gastrointestinal system, Application In Synthesis of 72509-76-3, the main research area is felodipine zein amorphous solid dispersion spray drying gastrointestinal system; TIM-1 model; Zein; amorphous solid dispersions; bioavailability; solid-state characterization; spray drying.

Felodipine has been widely used as a poorly water-soluble model drug for various studies to improve its oral bioavailability and in vivo efficacy. In this study, we developed amorphous solid dispersions (ASDs) via spray drying to enhance the bioavailability of felodipine through using natural zein protein as a novel polymeric excipient. The solid state characterization results demonstrated a single glass transition temperature (Tg) around 128.6°C and good phys. stability post 3 mo accelerated study under the condition of 40°C and 75% relative humidity (RH), which is possibly accounted for the mol. immobilization and hydrogen bonding interactions between felodipine and zein. By combining the in vitro dissolution study with TIM-1 gastrointestinal simulation investigation, it is indicated that felodipine was rapidly released from the ASD in 30 mins, and the supersaturation of felodipine was well maintained over 6 h, which resulted in a significant enhancement of felodipine bioavailability during simulated digestive processes in the upper GI tract. This study suggests that spray drying combined with natural excipient zein is an efficient formulation strategy for the development of ASDs with enhanced aqueous solubility and bioavailability.

Pharmaceutical Development and Technology published new progress about Crystal structure. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Application In Synthesis of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Luczynska, Katarzyna published the artcileVibrational Response of Felodipine in the THz Domain: Optical and Neutron Spectroscopy Versus Plane-Wave DFT Modeling, Application In Synthesis of 72509-76-3, the main research area is felodipine plane wave DFT modeling optical neutron spectrum review.

We present a joint exptl. and computational terahertz (THz) spectroscopy study of the most stable polymorph (form I) of an antihypertensive pharmaceutical solid, felodipine (FLD). The vibrational response has been analyzed at room temperature by combining optical (THz-TDS, FT-IR, THz-Raman) and neutron (INS) terahertz spectroscopy. With the challenging example of a large and flexible mol. solid, we illustrate the complementarity of the exptl. techniques. We show how the results can be understood by employing ab initio modeling and discuss current progress in the field. To this end, we employ plane wave formulation of d. functional theory (plane wave DFT) along with harmonic lattice dynamics calculations (HLD) and ab initio mol. dynamics (AIMD) simulations. Based on a comprehensive theor. anal., we discover an inconsistency in the commonly accepted structural model, which can be linked to a distinct librational dynamics of the side ester chains. As a result, only a moderate agreement with the exptl. spectra can be achieved. We, therefore, propose an alternative structural model, effectively accounting for the influence of the large-amplitude librations and allowing for a comprehensive anal. of the vibrational resonances up to 4.5 THz. In that way, we illustrate the applicability of the computationally supported THz spectroscopy to detect subtle structural issues in mol. solids. While the provided structural model can be treated as a guess, the problem calls for further revision by means of high-resolution crystallog. The problem also draws a need of extending the THz experiments toward low-temperature conditions and single-crystal samples. On the other hand, the studied system emerges as a challenge for the DFT modeling, being extremely sensitive to the level of the theory used and the resulting description of the intermol. forces. FLD form I can be, hence, considered as a testbed for the use of more sophisticated theor. approaches, particularly relying on an advanced treatment of the van der Walls forces and going beyond zero-temperature conditions and harmonic approximation

Journal of Infrared, Millimeter, and Terahertz Waves published new progress about Crystal structure. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Application In Synthesis of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hansen, Helge-Boj published the artcileThe Stronger the Better: Donor Substituents Push Catalytic Activity of Molecular Chromium Olefin Polymerization Catalysts, Category: pyridine-derivatives, the main research area is donor substituents chromium; chromium, ligand effects, olefin polymerization, supported catalysts, UHMW-PE.

The donor strength of bifunctional pyridine-cyclopentadienyl ligands was altered systematically by the introduction of donating groups in the para-position of the pyridine. In the resulting chromium complexes an almost linear correlation between donor strength and the nitrogen-chromium distance as well as the electronic absorption maximum is exptl. observed The connection of electron-donating groups in the ligand backbone leads to an efficient transfer of the electronic influences to the catalytically active metal center without restricting it through steric effects. Therefore, catalytic olefin polymerization activity, which is already very high for the previously studied catalysts, increase considerably by attaching para-amino groups to the chelating pyridine or quinoline, resp. Combining electron-rich indenyl ligands with para-amino substituted pyridines lead to the highest catalytic activities observed so far for this class of organo chromium olefin polymerization catalysts. The resulting polymers are of ultra-high mol. weight and the ability of the catalysts to incorporate co-monomers is also very high.

Chemistry – A European Journal published new progress about Crystal structure. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Li, Chengwei published the artcileStudy on Typical Diarylurea Drugs or Derivatives in Cocrystallizing with Strong H-Bond Acceptor DMSO, Name: Methyl 4-chloropicolinate, the main research area is diarylurea drug derivative cocrystn DMSO.

Diarylureas are widely used in self-assembly and supramol. chem. owing to their outstanding characteristics as both H-bond donors and acceptors. Unfortunately, this bonding property is rarely applied in the development of urea-containing drugs. Herein, seven related DMSO complexes were screened from 12 substrates involving sorafenib and regorafenib, mainly considering the substitution effect following a robust procedure. All complexes were structurally confirmed by spectroscopic means and thermal anal. Specially, five cocrystals with three deuterated, named sorafenib·DMSO, donafenib·DMSO, deuregorafenib·DMSO, 6·DMSO, and 7·DMSO were obtained. The crystal structures revealed that all host mols. consistently bonded with DMSO in intermol. interaction in a 1:1 stoichiometry. However, further comparison with documented DMSO complexes and parent motifs presented some arrangement diversities especially for 6·DMSO which offered a counter-example to previous rules. Major changes in the orientation of meta-substituents and the packing stability for sorafenib·DMSO and deuregorafenib·DMSO were rationalized by theory anal. and computational energy calculation Cumulative data implied that the planarization of two aryl planes in diarylureas may play a crucial role in cocrystn. Also, a polymorph study bridged the transformation between these ureas and their DMSO complexes.

ACS Omega published new progress about Cocrystallization. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, Name: Methyl 4-chloropicolinate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Boel, Eline published the artcileSolvent influence on manufacturability, phase behavior and morphology of amorphous solid dispersions prepared via bead coating, Related Products of pyridine-derivatives, the main research area is solvent manufacturability phase behavior morphol amorphous solid dispersion bead; Amorphous solid dispersion; Bead coating; Drug loading screening; Morphology; Solvent.

Bead coating or fluid-bed coating serves as an auspicious solvent-based amorphous solid dispersion (ASD) manufacturing technique in respect of minimization of potential phys. stability issues. However, the impact of solvent selection on the bead coating process and its resulting pellet formulation is, to the best of our knowledge, never investigated before. This study therefore aims to investigate the influence of the solvent on the bead coating process itself (i.e. manufacturability) and on solid-state characteristics of the resulting ASDs coated onto beads. For this purpose, the drug-polymer system felodipine (FEL)-poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) was coated onto microcrystalline cellulose (MCC) beads from acetonitrile (ACN), methanol (MeOH), ethanol (EtOH), acetone (Ac), 2-propanol (PrOH), dichloromethane (DCM) and Et acetate (EthAc). A drug loading screening approach with bead coating revealed analogus ability to manufacture high drug-loaded ASDs from the different organic solvents. The results show no correlation with crystallization tendency or with equilibrium solubility of the drug in the different solvents, nor with the solvent-dependent drug-polymer miscibility obtained from film casting experiments Distinct coating morphologies were however observed for PVP-VA and FEL-PVP-VA ASDs deposited onto beads from the various solvents, which is attributed to differences in solvent evaporation kinetics.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Coating materials. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Miura, Tomoaki published the artcileSupramolecular Control of the Spin-Dependent Dynamics of Long-Lived Charge-Separated States at the Micellar Interface As Studied by Magnetic Field Effect, Recommanded Product: 1,1-Di-n-octyl-4,4-bipyridinium Dibromide, the main research area is supramol spin dynamics charge separation micellar interface magnetic field.

Spin selectivity in long-lived charge separation at the micellar interface is studied using the magnetic field effect (MFE). An amphiphilic viologen is complexed with a nonionic surfactant to form a supramol. acceptor cage, of which the size is controlled by the acceptor concentration, as confirmed by dynamic light scattering measurement. Photoinduced electron transfer (ET) from a guest polyaromatic mol. to the viologen moiety is observed spin-dependently with time-resolved fluorescence (trFL) and transient absorption (TA). A neg. MFE on the radical yield is successfully observed, which indicates generation of singlet-born long-lived radical pair that is realized by supramol. control of the donor-acceptor (D-A) distances. The dominance of the singlet-precursor MFE is sensitive to the acceptor concentration, which presumably affects the D-A distance as well as the cage size. However, theor. anal. of the MFE gives large recombination rates of ca. 108 s-1, which indicate the contribution of spin-allowed recombination of the pseudocontact radical pair generated by still active in-cage diffusion. Dependence of the viologen concentration and alkyl chain length on the recombination and escape dynamics is discussed in terms of precursor spin states and the microenvironments in the cage.

Journal of Physical Chemistry B published new progress about Charge separation. 36437-30-6 belongs to class pyridine-derivatives, name is 1,1-Di-n-octyl-4,4-bipyridinium Dibromide, and the molecular formula is C26H42Br2N2, Recommanded Product: 1,1-Di-n-octyl-4,4-bipyridinium Dibromide.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kondo, Satoshi published the artcileSimultaneous Prediction of Intestinal Absorption and Metabolism Using the Mini-Ussing Chamber System, Computed Properties of 21829-25-4, the main research area is intestine absorption metabolism; intestinal absorption; intestinal metabolism; midazolam; mini-Ussing chamber; nifedipine; prediction; transport index (TI).

The purpose of this study was to investigate the possibility of simultaneous prediction of the intestinal absorption and metabolism in a mini-Ussing chamber equipped with rat intestinal tissues, based on the transport index (TI). TI value was defined as the sum of drug amounts, by mass balance method, transported to the basal-side component and drug amounts accumulated in the tissue, which are normalized by area under the curve of the drug in the apical compartment. Midazolam and nifedipine with high permeability were used as typical P 450 substrates to examine the possibility of simultaneous prediction of intestinal absorption and metabolism The metabolite formation of both compounds was observed and ketoconazole strongly inhibited the metabolite formation of both compounds in rat intestinal tissues, leading to the improvement of the TI value to a statistically significant extent for both compounds TI ratio of nifedipine between in the presence and absence of ketoconazole was larger than that of midazolam, which was consistent with the reported lower value of fraction absorbed multiplied by intestinal availability of nifedipine. Therefore, the mini-Ussing chamber, equipped with animal intestinal tissues, showed potential to predict the intestinal absorption and metabolism simultaneously.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Biological uptake. 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, Computed Properties of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem