Month: December 2022

Charwat, Verena published the artcileValidating the Arrhythmogenic Potential of High-, Intermediate-, and Low-Risk Drugs in a Human-Induced Pluripotent Stem Cell-Derived Cardiac Microphysiological System, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is ACS Pharmacology & Translational Science (2022), 5(8), 652-667, database is CAplus and MEDLINE.

Evaluation of arrhythmogenic drugs is required by regulatory agencies before any new compound can obtain market approval. Despite rigorous review, cardiac disorders remain the second most common cause for safety-related market withdrawal. On the other hand, false-pos. preclin. findings prohibit potentially beneficial candidates from moving forward in the development pipeline. Complex in vitro models using cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) have been identified as a useful tool that allows for rapid and cost-efficient screening of proarrhythmic drug risk. Currently available hiPSC-CM models employ simple two-dimensional (2D) culture formats with limited structural and functional relevance to the human heart muscle. Here, we present the use of our 3D cardiac microphysiol. system (MPS), composed of a hiPSC-derived heart micromuscle, as a platform for arrhythmia risk assessment. We employed two different hiPSC lines and tested seven drugs with known ion channel effects and known clin. risk: dofetilide and bepridil (high risk); amiodarone and terfenadine (intermediate risk); and nifedipine, mexiletine, and lidocaine (low risk). The cardiac MPS successfully predicted drug cardiotoxicity risks based on changes in action potential duration, beat waveform (i.e., shape), and occurrence of proarrhythmic events of healthy patient hiPSC lines in the absence of risk cofactors. We showcase examples where the cardiac MPS outperformed existing hiPSC-CM 2D models.

ACS Pharmacology & Translational Science published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, 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:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Berg, Ulf published the artcileTransition State Structural Variations in the Menshutkin Reaction. A Computational Study of Steric and Electronic Substituent Effects, COA of Formula: C6H8N2, the publication is Journal of Organic Chemistry (1995), 60(7), 1975-80, database is CAplus.

Transition structures for the gas phase S_N2 reactions of substituted pyridines with Me chloride, bromide, and iodide, resp., have been localized by the AMPAC program using the AM1 Hamiltonian. The reactions are strongly endothermic (ΔE ≈ 40-60 kcal/mol) and have activation barriers of ca. 70 kcal/mol, and the calculated order of leaving group (X) abilities is I < Br < Cl. The carbon-nitrogen bond is longer for the more reactive leaving group. The structural parameters are relatively insensitive to substitutions in the pyridine ring. Increasing the steric strain in the ortho position (Me to tert-Bu or 2,6-dimethyl) leads to looser and earlier transition states, whereas substitution with electron-withdrawing groups in the para position has very little effect on the transition structure. Solvent effects were briefly mimicked by means of a dipole placed on the N· · ·C· · ·X axis with the pos. charge pointing toward X. This results in a decrease of the activation barrier, a less endothermic reaction, earlier transition state, and a larger neg. charge on X. The consequences of steric effects in this reaction are discussed.

Journal of Organic Chemistry published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, COA of Formula: C6H8N2.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Prakash, Sekar published the artcileRhenium(I)-Catalyzed ortho-C-H Addition to Bicyclic Alkenes, Category: pyridine-derivatives, the publication is Chemistry – An Asian Journal (2018), 13(13), 1664-1668, database is CAplus and MEDLINE.

Hydroarylation of bicyclic alkenes was developed using a low-valent Re^I-catalyzed, directing group-assisted C-H bond activation strategy. The addition of sodium acetate significantly improves the reaction efficiency; moreover, bicyclic alkenes such as 7-oxa and aza benzonorbornadienes worked efficiently under this reaction condition. Preliminary mechanistic studies suggest that, after the alkene insertion, the rhenacycle preferentially undergoes protonolysis rather than reductive elimination.

Chemistry – An Asian Journal published new progress about 85237-71-4. 85237-71-4 belongs to pyridine-derivatives, auxiliary class Pyridine,Benzene, name is 5-Methyl-2-(p-tolyl)pyridine, and the molecular formula is C13H13N, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Lee, Kum-Tatt published the artcileUse of pyridine-2-aldehyde-2′-pyridylhydrazone for trace analysis of copper in foods, HPLC of Formula: 2215-33-0, the publication is Mikrochimica Acta (1976), 2(5-6), 505-13, database is CAplus.

Aqueous extracts of food were treated with a solution of pyridine-2-aldehyde-2′-pyridylhydrazone [2215-33-0] in 0.01M HCl (100 mg/100 ml) under slightly alk. conditions and the complex between Cu and the reagent was extracted with amyl alc. and the Cu content determined by colorimetry or by at. absorption. In tests with 0-10 mg Cu/20 g sugar and 0-20 μg/0.2 g defatted cocoa, 98-102% of the Cu was recovered by this method.

Mikrochimica Acta published new progress about 2215-33-0. 2215-33-0 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 2-((2-(Pyridin-2-yl)hydrazono)methyl)pyridine, and the molecular formula is C11H10N4, HPLC of Formula: 2215-33-0.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Kuduk, Scott D. published the artcileQuinolizidinone Carboxylic Acids as CNS Penetrant, Selective M₁ Allosteric Muscarinic Receptor Modulators, Safety of 2-Pyridinylboronic acid, the publication is ACS Medicinal Chemistry Letters (2010), 1(6), 263-267, database is CAplus and MEDLINE.

Pos. allosteric modulation of the M₁ muscarinic receptor represents an approach to treat the cognitive decline in patients with Alzheimer’s disease. Replacement of a quinolone ring system in a quinolone carboxylic acid series of M₁ modulators with a quinolizidinone bearing a basic amine linkage led to a series of compounds with higher free fraction, enhanced CNS exposure, and improved efficacy in rodent in vivo models of cognition.

ACS Medicinal Chemistry Letters published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Safety of 2-Pyridinylboronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Picado, Alfredo published the artcileA chemical probe for dark kinase STK17B derives its potency and high selectivity through a unique P-loop conformation, Product Details of C7H8BNO3, the publication is Journal of Medicinal Chemistry (2020), 63(23), 14626-14646, database is CAplus and MEDLINE.

STK17B is a member of the death-associated protein kinase family and has been genetically linked to the development of diverse diseases. However, the role of STK17B in normal and disease pathol. is poorly defined. Here, we present the discovery of thieno[3,2-d] pyrimidine SGC-STK17B-1 (11s), a high-quality chem. probe for this understudied “dark” kinase. 11S is an ATP-competitive inhibitor that showed remarkable selectivity over other kinases including the closely related STK17A. X-ray crystallog. of 11s and related thieno[3,2-d]pyrimidines bound to STK17B revealed a unique P-loop conformation characterized by a salt bridge between R41 and the carboxylic acid of the inhibitor. Mol. dynamic simulations of STK17B revealed the flexibility of the P-loop and a wide range of R41 conformations available to the apo-protein. The isomeric thieno[2,3-d]pyrimidine SGC-STK17B-1N (19g) was identified as a neg. control compound The >100-fold lower activity of 19g on STK17B was attributed to the reduced basicity of its pyrimidine N1.

Journal of Medicinal Chemistry published new progress about 2682066-26-6. 2682066-26-6 belongs to pyridine-derivatives, auxiliary class Boronic Acids,Boronic acid and ester,Boronic acid and ester, name is (6-Acetylpyridin-3-yl)boronic acid, and the molecular formula is C7H8BNO3, Product Details of C7H8BNO3.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Kindl, M. published the artcileScreening of phosphine ligands for anti-Markovnikov hydration of alkynes, Related Products of pyridine-derivatives, the publication is Chemicke Listy (2016), 110(11), 832-835, database is CAplus.

Hydration of C≃C bond is a very efficient synthetic step. Currently, there exist ruthenium catalytic complexes, preferably with phosphine or bipyridine ligands, able to hydrate with “anti-Markovnikov” selectivity, producing aldehydes. Although development of novel hydration catalysts was fruitful in recent years, only very few mechanistic studies of mol. structural influences are described. On the model hydration or 1-heptyne, we tested a series of various organophosphine ligands with various nitrogen functionalities having different acid-base properties. This screening showed that ligands with methylene-substituted nitrogen in five-membered ring are very promising to synthesize a catalyst for anti-Markovnikov hydration of alkynes.

Chemicke Listy published new progress about 338800-13-8. 338800-13-8 belongs to pyridine-derivatives, auxiliary class Bis-phosphine Ligands, name is 2,6-Bis((di-tert-butylphosphino)methyl)pyridine, and the molecular formula is C23H43NP2, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Dardir, Amira H. published the artcileSynthesis of Triarylmethanes via Palladium-Catalyzed Suzuki-Miyaura Reactions of Diarylmethyl Esters, Category: pyridine-derivatives, the publication is Organometallics (2021), 40(14), 2332-2344, database is CAplus and MEDLINE.

The synthesis of triarylmethanes via Pd-catalyzed Suzuki-Miyaura reactions between diarylmethyl 2,3,4,5,6-pentafluorobenzoates and aryl boronic acids is described. The system operates under mild conditions and has a broad substrate scope, including the coupling of diphenylmethanol derivatives that do not contain extended aromatic substituents. This is significant as these substrates, which result in the types of triarylmethane products that are prevalent in pharmaceuticals, have not previously been compatible with systems for diarylmethyl ester coupling. Also, the reaction can be performed stereospecifically to generate stereoinverted products. From DFT calculations, probably the oxidative addition of the diarylmethyl 2,3,4,5,6-pentafluorobenzoate substrate occurs via an S_N2 pathway, which results in the inverted products. Mechanistic studies indicate that oxidative addition of the diarylmethyl 2,3,4,5,6-pentafluorobenzoate substrates to (IPr)Pd(0) results in the selective cleavage of the O-C(benzyl) bond in part because of a stabilizing η³-interaction between the benzyl ligand and Pd. This is in contrast to previously described Pd-catalyzed Suzuki-Miyaura reactions involving Ph esters, which involve selective cleavage of the C(acyl)-O bond, because there is no stabilizing η³-interaction. It is anticipated that this fundamental knowledge will aid the development of new catalytic systems, which use esters as electrophiles in cross-coupling reactions.

Organometallics published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Guckian, Kevin published the artcilePyrazolone based TGFβR1 kinase inhibitors, Category: pyridine-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(1), 326-329, database is CAplus and MEDLINE.

Interruption of TGFβ signaling through inhibition of the TGFβR1 kinase domain may prove to have beneficial effect in both fibrotic and oncol. diseases. Herein we describe the SAR of a novel series of TGFβR1 kinase inhibitors containing a pyrazolone core. Most TGFβR1 kinase inhibitors described to date contain a core five-membered ring bearing N as H-bond acceptor. Described herein is a novel strategy to replace the core structure with pyrazolone ring, in which the carbonyl group is designed as an H-bond acceptor to interact with catalytic Lys 232.

Bioorganic & Medicinal Chemistry Letters published new progress about 197958-29-5. 197958-29-5 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester, name is 2-Pyridinylboronic acid, and the molecular formula is C5H6BNO2, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Renno, Giacomo published the artcileImidazo[1,5-a]pyridine-Based Fluorescent Probes: A Photophysical Investigation in Liposome Models, Safety of Phenyl(pyridin-2-yl)methanone, the publication is Molecules (2022), 27(12), 3856, database is CAplus and MEDLINE.

In this context, five imidazo[1,5-a]pyridine-based fluorophores were synthesized according to a one-pot cyclization between an aromatic ketone and benzaldehyde in the presence of ammonium acetate and acetic acid. The photophys. features of prepared compounds were investigated in several organic solvents and probes 2-4 exhibited the greatest solvatochromic behavior, resulting in a higher suitability as membrane probes. Their interaction with liposomes as artificial membrane model was tested showing a successful intercalation of the probes in the lipid bilayer. Kinetic experiments were carried out and the lipidic phase influence on the photophys. features was evaluated through temperature-dependent experiments The results herein reported encourage further investigations on the use of imidazo[1,5-a]pyridine scaffold as fluorescent membrane probes.

Molecules published new progress about 91-02-1. 91-02-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Benzene,Ketone, name is Phenyl(pyridin-2-yl)methanone, and the molecular formula is C12H9NO, Safety of Phenyl(pyridin-2-yl)methanone.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem