Month: December 2022

Mendes, Ana Karla Bittencourt published the artcile1α,25-(OH)2 vitamin D3 prevents insulin resistance and regulates coordinated exocytosis and insulin secretion, Category: pyridine-derivatives, the publication is Journal of Nutritional Biochemistry (2022), 108864, database is CAplus and MEDLINE.

Vitamin D₃ is associated with improvements in insulin resistance and glycemia. In this study, we investigated the short-term effect of 1α,25-(OH)₂ Vitamin D₃ (1,25-D₃) and cholecalciferol (vitamin D₃) on the glycemia and insulin sensitivity of control and dexamethasone-induced insulin-resistance rats. ⁴⁵Ca²⁺ influx responses to 1,25-D₃ and its role in insulin secretion were investigated in isolated pancreatic islets from control rats. In vivo, 5 d treatment with 1,25-D₃ (i.p.) prevented insulin resistance in dexamethasone-treated rats. Treatment with 1,25-D₃ improved the activities of hepatic enzymes, serum lipids and calcium concentrations in insulin-resistant rats. 25-D₃ (o.g.) does not affect insulin resistance. In pancreatic islets, 1,25-D₃ increased insulin secretion and stimulated rapid response ⁴⁵Ca²⁺ influx. The stimulatory effect of 1,25-D₃ on ⁴⁵Ca²⁺ influx was decreased by diazoxide, apamine, thapsigargin, dantrolene, 2-APB, nifedipine, TEA, PKA, PKC, and cytoskeleton inhibitor, while it was increased by glibenclamide and N-ethylmaleimide. The stimulatory effect of 1,25-D₃ on ⁴⁵Ca²⁺ influx involves the activation of L-type VDCC, K⁺-ATP, K⁺-Ca²⁺, and Kv channels, which augment cytosolic calcium. These ionic changes mobilize calcium from stores and downstream activation of PKC, PKA tethering vesicle traffic and fusion at the plasma membrane for insulin secretion. This is the first study highlighting the unprecedented role of 1,25-D₃ (short-term effect) in the regulation of glucose homeostasis and on prevention of insulin resistance. Furthermore, this study shows the intracellular β-cell signal transduction of 1,25-D₃ through the modulation of pivotal ionic channels and proteins exhibiting a coordinated exocytosis of vesicles for insulin secretion.

Journal of Nutritional Biochemistry 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, Category: pyridine-derivatives.

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

Adamek, Rebecca N. published the artcileHydroxypyridinethione Inhibitors of Human Insulin-Degrading Enzyme, Recommanded Product: 2-Bromopyridin-3-amine, the publication is ChemMedChem (2021), 16(11), 1775-1787, database is CAplus and MEDLINE.

Insulin-degrading enzyme (IDE) is a human mononuclear Zn2+-dependent metalloenzyme that is widely regarded as the primary peptidase responsible for insulin degradation Despite its name, IDE is also critically involved in the hydrolysis of several other disparate peptide hormones, including glucagon, amylin, and the amyloid β-protein. As such, the study of IDE inhibition is highly relevant to deciphering the role of IDE in conditions such as type-2 diabetes mellitus and Alzheimer disease. There have been few reported IDE inhibitors, and of these, inhibitors that directly target the active-site Zn2+ ion have yet to be fully explored. In an effort to discover new, zinc-targeting inhibitors of IDE, a library of âˆ?50 metal-binding pharmacophores was screened against IDE, resulting in the identification of 1-hydroxypyridine-2-thione (1,2-HOPTO) as an effective Zn2+-binding scaffold. Screening a focused library of HOPTO compounds identified 3-sulfonamide derivatives of 1,2-HOPTO as inhibitors of IDE (Ki values of âˆ?0μM). Further structure-activity relationship studies yielded several thiophene-sulfonamide HOPTO derivatives with good, broad-spectrum activity against IDE that have the potential to be useful pharmacol. tools for future studies of IDE.

ChemMedChem published new progress about 39856-58-1. 39856-58-1 belongs to pyridine-derivatives, auxiliary class Pyridine,Bromide,Amine, name is 2-Bromopyridin-3-amine, and the molecular formula is C5H5BrN2, Recommanded Product: 2-Bromopyridin-3-amine.

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

Kakehi, Akikazu published the artcilePreparation of new nitrogen-bridged heterocycles. 72. A new approach to 1-acyl-3-(substituted methylthio)thieno[3′,4′:4,5]imidazo[1,5-a]pyridine derivatives, HPLC of Formula: 17281-59-3, the publication is Chemical & Pharmaceutical Bulletin (2010), 58(11), 1502-1510, database is CAplus and MEDLINE.

The alk. treatment of the pyridinium salts, readily available from the S-alkylation of 3-amino-4-(1-pyridinio)thiophene-5-thiolates with various alkyl halides, in chloroform at room temperature afforded the corresponding thieno[3′,4′:4,5]imidazo[1,2-a]pyridine derivatives, e.g., I (R = Ph, 4-ClC₆H₄, OEt, etc., R⁴ = H, Me, PhCH₂, Ph, etc.), in low to moderate yields via the intramol. cyclization of the resulting 1,5-dipoles followed by the aromatization of the primary cycloadducts. Interestingly, the reactions using unsym. 3-amino-4-[1-(3-methylpyridinio)]thiophene-5-thiolates afforded only 8-methylthieno[3′,4′:4,5]imidazo[1,2-a]pyridines and the other 6-Me derivatives were not formed at all. In addition, the isolation of a byproduct in the condensation reaction of pyridinium salt with the solvent (CHCl₃) is also discussed.

Chemical & Pharmaceutical Bulletin published new progress about 17281-59-3. 17281-59-3 belongs to pyridine-derivatives, auxiliary class Pyridine,Nitrile,Salt, name is 1-(Cyanomethyl)pyridin-1-ium chloride, and the molecular formula is C7H7ClN2, HPLC of Formula: 17281-59-3.

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

Kakehi, Akikazu published the artcilePreparation of new nitrogen-bridged heterocycles. 60. Syntheses and conformational analyses of bis(indolizin-1-yl) disulfides, HPLC of Formula: 17281-59-3, the publication is Chemical & Pharmaceutical Bulletin (2007), 55(10), 1458-1465, database is CAplus and MEDLINE.

Bis(indolizin-1-yl) disulfides I (R = cyano, CO₂Et, COPh, R¹ = Me, Et, CH₂Ph, etc., R² = H, Me), readily obtainable from the treatment of 1-(benzoylthio)indolizines II with piperidine, were prepared and their conformations were investigated. In comparison with those of 1-(benzoylthio)indolizines, the ¹H-NMR spectra of these disulfides showed considerable high field shifts (δ 0.13-0.82 ppm) on each pyridine ring proton and the UV spectra exhibited significant bathochromic and hyperchromic shifts. These results supported strongly the participation of an intramol. π-π interaction between two indolizine rings in these mols. and, hence, of a particular gauche (cis) conformation. However, the conformational considerations and mol. calculations (Mopac PM3) for some bis(indolizin-1-yl) disulfides showed the presence of four more stable gauche forms in which two are enantiomeric, resulting in three types of gauche structures. These three types of gauche structures were confirmed by X-ray analyses.

Chemical & Pharmaceutical Bulletin published new progress about 17281-59-3. 17281-59-3 belongs to pyridine-derivatives, auxiliary class Pyridine,Nitrile,Salt, name is 1-(Cyanomethyl)pyridin-1-ium chloride, and the molecular formula is C7H7ClN2, HPLC of Formula: 17281-59-3.

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

Shin, Youngsook published the artcileDiscovery, Optimization, and in Vivo Evaluation of Benzimidazole Derivatives AM-8508 and AM-9635 as Potent and Selective PI3Kδ Inhibitors, Recommanded Product: 2-Pyridinylboronic acid, the publication is Journal of Medicinal Chemistry (2016), 59(1), 431-447, database is CAplus and MEDLINE.

Lead optimization efforts resulted in the discovery of two potent, selective, and orally bioavailable PI3Kδ inhibitors, 1 (AM-8508) and 2 (AM-9635), with good pharmacokinetic properties. The compounds inhibit B cell receptor (BCR)-mediated AKT phosphorylation (pAKT) in PI3Kδ-dependent in vitro cell based assays. These compounds which share a benzimidazole bicycle are effective when administered in vivo at unbound concentrations consistent with their in vitro cell potency as a consequence of improved unbound drug concentration with lower unbound clearance. Furthermore, the compounds demonstrated efficacy in a Keyhole Limpet Hemocyanin (KLH) study in rats, where the blockade of PI3Kδ activity by inhibitors 1 and 2 led to effective inhibition of antigen-specific IgG and IgM formation after immunization with KLH.

Journal of Medicinal Chemistry 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 C19H14Cl2, Recommanded Product: 2-Pyridinylboronic acid.

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

Battula, S. R. K. published the artcileA mild and efficient copper-catalyzed N-arylation of unprotected sulfonimidamides using boronic acids, Formula: C5H6BNO2, the publication is Tetrahedron Letters (2014), 55(2), 517-520, database is CAplus.

An efficient and low cost copper catalyzed system for N-arylation of sulfonimidamides was developed. The reaction proceeds at room temperature under base free conditions. Various N-aryl, N-heteroaryl, and N-cyclopropyl sulfonimidamides were obtained in good to excellent yields.

Tetrahedron 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, Formula: C5H6BNO2.

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

Wall, Mark J. published the artcileDiscovery and optimization of a novel series of pyrazolyltetrahydropyran N-type calcium channel (Ca_v 2.2) blockers for the treatment of pain, HPLC of Formula: 612845-44-0, the publication is Bioorganic & Medicinal Chemistry Letters (2018), 28(23-24), 3780-3783, database is CAplus and MEDLINE.

A novel series of pyrazolyltetrahydropyran N-type calcium channel blockers are described. Structural modifications of the series led to potent compounds in both a cell-based fluorescent calcium influx assay and a patch clamp electrophysiol. assay. Representative compounds from the series were bioavailable and showed efficacy in the rat CFA and CCI models of inflammatory and neuropathic pain.

Bioorganic & Medicinal Chemistry Letters published new progress about 612845-44-0. 612845-44-0 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester,Ether,Boronic Acids,Boronic acid and ester, name is (6-Ethoxypyridin-3-yl)boronic acid, and the molecular formula is C6H16OSi, HPLC of Formula: 612845-44-0.

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

Xu, Yuqin published the artcileThe Chan-Evans-Lam N-arylation of phosphonic/phosphinic amides, Synthetic Route of 197958-29-5, the publication is Tetrahedron (2017), 73(31), 4602-4609, database is CAplus.

A stoichiometric copper(II)-mediated arylation protocol of phosphinamides and phosphonamides was herein demonstrated. Various unreported N-aryl phosphinamides and phosphonamides were successfully prepared through Chan-Evans-Lam reaction with high efficiency (up to 88% yields) and good functional groups tolerance (30 examples) in the absence of any ligands or co-catalysts.

Tetrahedron 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 C13H26N2, Synthetic Route of 197958-29-5.

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

Yu, Miao published the artcileA Practical and Robust Multistep Continuous Process for Manufacturing 5-Bromo-N-(tert-butyl)pyridine-3-sulfonamide, Product Details of C5H5NO3S, the publication is Organic Process Research & Development (2019), 23(9), 2088-2095, database is CAplus.

A multistep continuous flow process involving (1) magnesium-halogen exchange, (2) sulfonylation with sulfuryl chloride, and (3) reaction with tert-butylamine was developed for the synthesis of an arylsulfonamide pharmaceutical intermediate in the synthesis of BMS-919373. The process was successfully implemented, including a robust control strategy to manage the levels of several process impurities, to produce 76 kg of 5-bromo-N-(tert-butyl)pyridine-3-sulfonamide (I). As the instability of the reactive intermediates and existence of strong exotherms made a batch process unsuitable for production beyond a 1 kg scale, the alternative continuous process led to a practical and robust manufacturing route to the active pharmaceutical ingredient.

Organic Process Research & Development published new progress about 636-73-7. 636-73-7 belongs to pyridine-derivatives, auxiliary class Pyridine,Sulfonic acid, name is Pyridine-3-sulfonic acid, and the molecular formula is C23H20BN, Product Details of C5H5NO3S.

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

Kiselyov, Alexander S. published the artcileA novel synthesis of 2-substituted pyrido[1,2-a]-1,3,5-triazin-4-ones by the reaction of N-fluoropyridinium salts with cyanate ion and carbonitriles: evidence in support of a carbene intermediate, Product Details of C6H5F4NO3S, the publication is Tetrahedron Letters (1994), 35(2), 207-10, database is CAplus.

A carbene intermediate derived from N-fluoropyridinium cation is suggested in the novel synthesis of pyridotriazines I (R¹ = Pr, CMe₃, Ph) by the reaction of N-fluoropyridinium salts with cyanate ion and R¹CN.

Tetrahedron Letters published new progress about 107263-95-6. 107263-95-6 belongs to pyridine-derivatives, auxiliary class Fluorination reagent, name is 1-Fluoropyridiniumtriflate, and the molecular formula is C6H5F4NO3S, Product Details of C6H5F4NO3S.

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