96-50-4Relevant articles and documents
Diazotisation Mechanism of Heteroaromatic Amines. Diazotisation of 2-Aminothiazole as an Equilibrium
Diener, Heinz,Guelec, Bilge,Skrabal, Peter,Zollinger, Heinrich
, p. 800 - 805 (1989)
The rate of diazotisation of 2-aminothiazole was measured in 65 to 75 percent (w/w) aqueous H2SO4.The kinetic solvent isotope effect of the diazotisation in 72 percent D2SO4/D2O was determined (kH/kD = 5.8+/-0.2).These data are consistent with a mechanism in which the 2-aminothiazole, protonated at the ring N-atom, but not at the NH2 group, is attacked by the NO+ ion.The reaction does not go to completion, but to an equilibrium.The equilibrium concentration of the diazonium ion was determined in 30, 50, 70, and 90 percent (w/w) H2SO4 at three initial concentrations of reagents (0.001, 0.01, and 0.1 M).The final concentrations of the reagents and the diazonium ion are consistent with a reversible process.This is the first diazotisation for which quantitative evidence for equilibration has been found.In the very large range of acidities used (H0 = -1.73 to -9.01), it was not possible to calculate meaningful equilibrium constants that are independent of the acidity.
Synthesis of 6-membered-ring fused thiazine-dicarboxylates and thiazole-pyrimidines via one-pot three-component reactions
Bode, Moira L.,Coyanis, Elena Mabel,Fernandes, Manuel A.,Fish, Muhammad Q.,Mohlala, Reagan L.
, (2021/09/18)
A facile and efficient one-pot three-component reaction method for the synthesis of thiazine-dicarboxylates is reported. Reaction of an isocyanide and dialkyl acetylenedicarboxylate with 2-amino-4H-1,3-thiazin-4-one derivatives containing both an acidic proton and an internal nucleophile gave the products in good yields of 76–85%. The reactivity of dialkyl acetylenedicarboxylates was further tested in the synthesis of thiazole-pyrimidines where a two-component reaction of 2-aminothiazole with dialkyl acetylenedicarboxylates was successfully converted to a more efficient three-component reaction of a thiourea, α-haloketone and dialkyl acetylenedicarboxylate (DMAD/DEtAD) to give thiazole-pyrimidines in good yields of 70–91%.
SUBSTITUTED IMIDAZOLES FOR THE INHIBITION OF TGF-BETA AND METHODS OF TREATMENT
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Paragraph 0079, (2020/03/15)
This disclosure relates to low molecular weight substituted imidazoles that inhibit the TGF-b signaling pathway. More specifically, this disclosure relates to methods of using said imidazoles for the treatment of diseases related to the TGF-b signaling pathways including, but not limited to, atherosclerosis, Marfan syndrome, Loeys-Dietz syndrome, obesity, diabetes, multiple sclerosis, keratoconus, idiopathic pulmonary fibrosis, Alzheimer's Disease, chronic kidney disease, and scleroderma.
Novel synthesized SLC-0111 thiazole and thiadiazole analogues: Determination of their carbonic anhydrase inhibitory activity and molecular modeling studies
Abo-Ashour, Mahmoud F.,Eldehna, Wagdy M.,Nocentini, Alessio,Ibrahim, Hany S.,Bua, Silvia,Abdel-Aziz, Hatem A.,Abou-Seri, Sahar M.,Supuran, Claudiu T.
, p. 794 - 802 (2019/04/13)
In the presented work, we report the design and synthesis of novel SLC-0111 thiazole and thiadiazole analogues (11a–d, 12a–d, 16a–c and 17a–d). A bioisosteric replacement approach was adopted to replace the 4-fluorophenyl tail of SLC-0111 with thiazole and thiadiazole ones, which were thereafter extended with lipophilic un/substituted phenyl moieties. All the newly synthesized SLC-0111 analogues were evaluated in vitro for their inhibitory activity towards a panel of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms (hCA I, II, IX and XII), using a stopped-flow CO2 hydrase assay. All the examined isoforms were inhibited by the primary sulfonamide derivatives (11a–d and 12a–d) in variable degrees with the following KI ranges: 162.6–7136 nM for hCA I, 9.0–833.6 nM for hCA II, 7.9–153.0 nM for hCA IX, and 9.4–94.0 nM for hCA XII. In particular, compounds 12b and 12d displayed 5.5-fold more potent inhibitory activity (KIs = 8.3 and 7.9 nM, respectively) than SLC-0111 (KI = 45 nM) towards hCA IX. Molecular docking study was carried out for 12d within the hCA IX (PDB 3IAI) active site, to justify its inhibitory activity.
Hg2+ induced hydrolysis of thiazole amine based Schiff base: Colorimetric and fluorogenic chemodosimeter for Hg2+ ions in an aqueous medium
Tekuri, Venkatadri,Sahoo, Suban K.,Trivedi, Darshak R.
, p. 19 - 26 (2019/04/05)
Simple pyrene-based chemosensors 1 to 3, were synthesized from pyrene-1-carboxaldehyde and they were characterized using various spectroscopic techniques like UV–Vis, FT-IR, Mass, 1H NMR and 13C NMR. Among synthesized receptors, the receptor 1 shows high selectivity towards Hg2+ ions. Further, the high selectivity of receptor 1 towards Hg2+ ions in the presence of various other interfering metal ions like Ni2+, Zn2+, Mn2+, Co2+, Cu2+, Cr3+, Fe3+, Al3+, Ag+, Fe2+, Cd2+, Mg2+, Pb2+, Ca2+, Na+, K+ was confirmed by UV–Vis and fluorescence methods. The detection limit for Hg2+ ions was found to be 0.270 μM. The chemodosimetric irreversible hydrolysis of the receptor 1 in the presence of Hg2+ was studied by UV/Vis, fluorescence, FT-IR, LC-MS, 1H NMR and theoretical DFT study. Further, the real life applications of receptor 1 for the determination of Hg2+ ions were demonstrated by UV–Vis method.
Imidazole-thiazole coupled derivatives as novel lanosterol 14-α demethylase inhibitors: ionic liquid mediated synthesis, biological evaluation and molecular docking study
Nikalje, Anna Pratima G.,Tiwari, Shailee V.,Sarkate, Aniket P.,Karnik, Kshipra S.
, p. 592 - 606 (2017/11/06)
A novel series of imidazole-thiazole coupled derivatives (7a–7q) were synthesized using Green protocol and identified by different spectroscopic techniques. The synthesized derivatives (7a–7q) were evaluated for their in vitro antifungal activity against the six fungi strains. The compounds 7j and 7k exhibited the most promising antifungal activity. The compound 7k exhibited extremely high antifungal activity against C. albicans, C. glabrata, F. oxysporum, A. flavus, A. niger, and C. neoformans with MIC80 values of 0.2, 0.2, 20, 35, 40, and 5 μg/ml respectively. The mode of action of the most promising antifungal compounds 7j and 7k was established by ergosterol extraction and quantitation assay. From the ergosterol extraction and quantitation assay it was found that the compounds 7j and 7k act by inhibition of ergosterol biosynthesis in C. albicans. The molecular docking study revealed the high spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which proves that the tested compounds inhibit the synthesis of lanosterol 14α-demethylase. The synthesized compounds were analyzed for ADMET properties to establish oral drug like behavior and shows satisfactory results. To establish the antifungal selectivity and safety, the most active compounds were further tested for cytotoxicity against human cancer cell lines HeLa and K-562 and were found to be non-cytotoxic in nature. The in vivo acute oral toxicity study was performed for the most active compounds and results indicate that the compounds are non-toxic in nature.
Metal-free C(sp2)-H functionalization of azoles: K2CO3/I2-mediated oxidation, imination, and amination
Das, Ranajit,Banerjee, Mainak,Rai, Rakesh Kumar,Karri, Ramesh,Roy, Gouriprasanna
, p. 4243 - 4260 (2018/06/22)
The direct C2-H oxidation and imination of a wide variety of azoles was achieved by using a commercially available simple K2CO3/I2 reagent combination. The iodinated azole adduct, produced via the in situ generation of N-heterocyclic carbene, is the key intermediate for C2-H oxidation, imination, and amination of azoles. Significantly, these reactions proceed under mild conditions with high to excellent yields, are scalable to large quantity and exhibit a broad substrate scope. Interestingly, this direct C2-H imination method allowed us to access various pharmacologically active N6-alkyl or N6-aryl substituted benzimidazoquinazolinone scaffolds through intramolecular C-H imination in a sequential one-pot reaction.
Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures
Islam, Saidul,Bu?ar, Dejan-Kre?imir,Powner, Matthew W.
, p. 584 - 589 (2017/05/31)
A central problem for the prebiotic synthesis of biological amino acids and nucleotides is to avoid the concomitant synthesis of undesired or irrelevant by-products. Additionally, multistep pathways require mechanisms that enable the sequential addition of reactants and purification of intermediates that are consistent with reasonable geochemical scenarios. Here, we show that 2-aminothiazole reacts selectively with two- and three-carbon sugars (glycolaldehyde and glyceraldehyde, respectively), which results in their accumulation and purification as stable crystalline aminals. This permits ribonucleotide synthesis, even from complex sugar mixtures. Remarkably, aminal formation also overcomes the thermodynamically favoured isomerization of glyceraldehyde into dihydroxyacetone because only the aminal of glyceraldehyde separates from the equilibrating mixture. Finally, we show that aminal formation provides a novel pathway to amino acids that avoids the synthesis of the non-proteinogenic α,α-disubstituted analogues. The common physicochemical mechanism that controls the proteinogenic amino acid and ribonucleotide assembly from prebiotic mixtures suggests that these essential classes of metabolite had a unified chemical origin.
Nanostarch: a novel and green catalyst for synthesis of 2-aminothiazoles
Safari, Javad,Sadeghi, Masoud
, p. 745 - 749 (2017/03/17)
Abstract: In this work, starch nanoparticles as a green and cheap catalyst were obtained based on the precipitation of amorphous starch in ethanol. It was found that starch nanoparticles are efficient catalyst for the synthesis of 2-aminothiazoles using methylcarbonyl compounds and thiourea as precursors. The use of green and biodegradable nanostarch makes this present methodology quite simple, shorter reaction times and milder conditions, and more convenient and economically viable compared to catalyzed methods reported in the literature. Graphical abstract: [Figure not available: see fulltext.]
Synthesis of thiazole linked indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors
Guggilapu, Sravanthi Devi,Guntuku, Lalita,Reddy, T. Srinivasa,Nagarsenkar, Atulya,Sigalapalli, Dilep Kumar,Naidu,Bhargava, Suresh K.,Bathini, Nagendra Babu
, p. 83 - 95 (2017/06/27)
A series of thiazole linked indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 13d displayed cytotoxicity of IC50 = 93 nM towards DU145 cancer cell line. The most active compound 13d was also tested on RWPE-1 cells and was found to be safe compared to the DU145 cells. The target compounds were also evaluated for their inhibition activity of tubulin polymerization. Further, the treatment of compound 13d on DU145 cells led to the inhibition of cell migration ability. The detailed studies such as acridine orange/ethidium Bromide (AO/EB), DAPI, annexin V-FITC/propidium iodide staining assay suggested that the compound 13d induced apoptosis in DU145 cells. The influence of the cytotoxic compound 13d on the cell cycle distribution was assessed on the DU145 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, the treatment with compound 13d caused collapse of mitochondrial membrane potential and elevated intracellular ROS levels in DU145 cells. The results from molecular modelling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Thus, this new molecular scaffold could be a new lead for the development of anticancer agents that target tubulin.
