Pyridine Ether Research Articles

Molecular docking-based interaction studies on imidazo[1,2-a] pyridine ethers and squaramides as anti-tubercular agents

ABSTRACT Development of new anti-tubercular agents is required in the wake of resistance to the existing and newly approved drugs through novel-validated targets like ATP synthase, etc. The major limitation of poor correlation between docking scores and biological activity by SBDD was overcome by a novel approach of quantitatively correlating the interactions of different amino acid residues present in the target protein structure with the activity. This approach well predicted the ATP synthase inhibitory activity of imidazo[1,2-a] pyridine ethers and squaramides (r = 0.84) in terms of Glu65b interactions. Hence, the models were developed on combined (r = 0.78), and training (r = 0.82) sets of 52, and 27 molecules, respectively. The training set model well predicted the diverse dataset (r = 0.84), test set (r = 0.755), and, external dataset (r ext = 0.76). This model predicted three compounds from a focused library generated by incorporating the essential features of the ATP synthase inhibition with the pIC50 values in the range of 0.0508–0.1494 µM. Molecular dynamics simulation studies ascertain the stability of the protein structure and the docked poses of the ligands. The developed model(s) may be useful in the identification and optimization of novel compounds against TB.

Two novel Co (II) bifunctional MOFs: Syntheses and applications in photocatalytic degradation of dyes and electrocatalytic water oxidation

Two novel Co (II) MOFs based on 5-(4-(imidazolyl-1-yl)phenyl) isophthalic acid (H2L), namely [Co(L)(tib)(H2O)2]n (CP 1) and [Co(L)(bip)0.5]n (CP 2) (tib ​= ​1,3,5-tirs (1-imidazolyl) benzene, bip ​= ​3,5-bis(1-imidazolyl) pyridine ether) have been synthesized under solvothermal conditions and characterized by powder X-ray diffraction, single crystal X-ray diffraction. The photodegradation studies demonstrate that CPs 1–2 show high-efficiency degradation of MV (Methyl violet), and the mechanism studies demonstrate that the main active species are ⋅OH radicals. Meanwhile, electrochemistry studies demonstrate that CPs 1–2 can catalyze water oxidation under alkaline conditions, and CPs 1–2 only need the overpotential of 348 ​mV–760 mV to deliver the current density of 1 ​mA ​cm−2.

Hypervalent iodine mediated synthesis of imidazo[1,2-a]pyridine ethers: consecutive methylene linkage and insertion of ethylene glycol

Hypervalent iodine mediated selective synthesis of imidazo[1,2-a]pyridine ethers using ethylene glycol as a methoxy ethanol source as well as solvent under metal-free conditions is described.

New fluorinated copoly(pyridine ether imide)s derived from 4,4′-oxydianiline, pyromellitic dianhydride and 4-(4-trifluoromethylphenyl)-2,6-bis[4-(4-amino-2-trifluoromethylphenoxy)phenyl]pyridine

A new aromatic diamine, 4-(4-trifluoromethylphenyl)-2,6-bis[4-(4-amino-2-trifluoromethylphenoxy)phenyl]pyridine (9FPBAPP), was prepared from 4-(4-trifluoromethylphenyl)-2,6-bis(4-hydroxyphenyl)pyridine with 2-chloro-5-nitrotrifluoromethylbenzene by substitution and reduction reactions successively. A series of fluorinated copoly(pyridine ether imide)s were prepared from 4,4′-oxydianiline (ODA), pyromellitic dianhydride and 9FPBAPP by thermal imidization procedure with various mole ratios of ODA and 9FPBAPP. All polymers were amorphous and soluble in organic solvents such as N,N-dimethylacetamide and N-methyl-2-pyrrolidone, and had Tgs of 285.8–310.0 °C, 5% weight loss temperature of 545.5–565.7 °C in nitrogen atmosphere. Tough and flexible polymer films also exhibited excellent mechanical properties with tensile strengths of 76.3–96.5 MPa, tensile moduli of 1.3–1.8 GPa, elongations at break of 15.6–25.1%, low dielectric constants of 3.04–3.51 (1 MHz) and water uptake of 0.44–0.65%, as well as high optical transparency with an ultraviolet–visible absorption cutoff wavelength in the 382–412 nm range.

Soluble copoly(pyridine ether imide)s derived from 6FDA, 1,4-bis(4-amino-2-trifluromethylphenoxy)benzene, and 4-(4-trifluoromethylphenyl)-2,6-bis(4-aminophenyl)pyridine

A series of new fluorinated copoly(pyridine ether imide)s were prepared by thermal imidization of polyamide acid derived from 1,4-bis(4-amino-2-trifluoromethylphenoxy)benzene (BATB), 4-(4-trifluoro...

Discovery of Imidazo[1,2-a]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis.

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure-activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection.

Active Metal Template Synthesis of [2]Catenanes

The synthesis of [2]catenanes by single macrocyclization and double macrocyclization strategies using Cu(I) ions to catalyze covalent bond formation while simultaneously acting as the template for the mechanically interlocked structure is reported. These "active metal template" strategies employ appropriately functionalized pyridine ether or bipyridine ligands and either the CuAAC "click" reaction of azides with terminal alkynes or the Cu(I)-mediated Cadiot-Chodkiewicz heterocoupling of an alkyne halide with a terminal alkyne. Using one macrocyclic and one acyclic building block, heterocircuit (the rings are constitutionally different) [2]catenanes are produced via the single macrocyclization route in up to 53% yield by optimizing the reaction conditions and relative stoichiometry of the starting materials. Alternatively, with the active template CuAAC reaction, a single acyclic unit can be used to form a homocircuit (two identical rings) [2]catenane in 46% yield through a one-pot, double macrocyclization, procedure. Remarkably, <7% of the corresponding noninterlocked macrocycle is isolated from this reaction, indicating the efficacy of Cu(I) as both a template for the catenane and a catalyst for covalent bond formation in the reaction.

ADDP and PS-PPh3: an efficient Mitsunobu protocol for the preparation of pyridine ether PPAR agonists.

A series of pyridine ether PPAR agonists were synthesized through an ADDP and PS-PPh3 modified Mitsunobu protocol, which eliminated significant by-product formation. This method proved to be versatile, efficient and amenable to parallel synthesis.

Intermolecular Palladium‐Catalyzed Coupling of 2‐Halopyridines and Alcohols for the Preparation of Pyridine Ether PPAR Agonists.

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Intermolecular palladium-catalyzed coupling of 2-halopyridines and alcohols for the preparation of pyridine ether PPAR agonists

A series of pyridine ether PPAR agonists were synthesized through intermolecular palladium-catalyzed coupling of 2-halopyridines and alcohols. This method proved to be versatile, efficient, and amenable to parallel synthesis.

Cyclic poly(pyridine ether)s by the polycondensation of 2,6‐difluoropyridine with various diphenols

AbstractThe bistrimethylsilyl derivatives of six different diphenols were polycondensed with 2,6‐difluoropyridine in N‐methylpyrrolidone in the presence of K2CO3. On the basis of previous studies, the reaction conditions were optimized for almost quantitative conversions. The feed ratio was systematically varied to optimize the molecular weight. A 2 mol % excess of 2,6‐difluoropyridine was needed to obtain maximum molecular weights. In the matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectra of the optimized polyethers, only cycles were found (detectable up to 5000 Da). Obviously, the relatively low molecular weights obtained under optimized conditions resulted from a limitation of the chain growth by cyclization, indicating a high cyclization tendency for poly(pyridine ether)s. The size exclusion chromatography measurements not only proved low molecular weights but also demonstrated the existence of bimodal mass distributions and high polydispersities. Protonation of the poly(pyridine ether)s required strong acids such as methane or trifluoromethane sulfonic acid. The solubilities of the neutral and protonated polyethers derived from bisphenol A were studied in various solvents. The MALDI‐TOF mass spectra proved that protonation at 20–25 °C did not cause cleavage of ether bonds. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4781–4789, 2005

Multicyclic polyethers derived from 1,1,1‐tris(4‐hydroxyphenyl)ethane and 2,6‐dihalopyridines

AbstractPoly(pyridine ether)s were prepared in two ways: the polycondensation of silylated 1,1,1‐tris(4‐hydroxyphenyl)ethane (THPE) with 2,6‐difluoropyridine (method A) and the polycondensation of free THPE with 2,6‐dichloropyridine (method B). With method A, the THPE/difluoropyridine feed ratio was varied from 1.0:1.0 to 1.0:1.6. Cycles, bicycles, and multicycles were the main reaction products, and crosslinking was never observed. When ideal stoichiometry was used exclusively, multicycles free of functional groups were obtained. These multicycles were detectable in matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectra up to B38C76 with a mass of approximately 32,000 Da. With method B, the reaction conditions were varied at a fixed feed ratio to achieve an optimum for the preparation of multicyclic polyethers, but because of the lower reactivity of 2,6‐dichloropyridine, a quantitative conversion was not achieved. The reaction products were characterized with MALDI‐TOF mass spectrometry, viscosity measurements, and size exclusion chromatography. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5725–5735, 2004

New polymer syntheses. 58. Alkylation of aromatic poly(pyridine ethers) and their application as membranes

After opftimization of the reaction conditions, several fpoly(pyridine ether)s and poly(pyridine ether sulfone)s were almost quantitatively methylated with dimethyl sulfate in nitrobenzene. DSC and WAXS data indicated that most methylated poly(pyridinium ether)s are amorphous materials with higher T g than those of the parent polyethers. The solubilities of all poly(pyridinium ether)s in various solvents were studied. A membrane based on one methylated poly(pyridinium ether sulfone) exhibited high permselectivity for CO 2 /CH 4 and He/N 2