- Single crystal X-ray of 1-[(1,2,4-triazole-4-yl)imino]diacetyl monoxime (L) as a novel triazole and the characterization and biological studies of its chelates of Co2+, Pd2+, and Fe3+
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A novel and efficient synthesis of 1-[(1,2,4-triazole-4-yl)imino]diacetyl monoxime (L) is described. The advantages of this method are that it is inexpensive, the starting reactants are readily available, and it has good yield and short reaction times. The hull of the product was suggested by elemental analyses, spectral and single crystal X-ray. Novel Co2+, Pd2+, and Fe3+ chelates derived from L were characterized by Fourier transform infrared spectroscopy, suggesting that L acts as bidentate via the two azomethine groups. Tetrahedral geometry for Fe3+ and Co2+ and square-planar geometry around the Pd2+ chelate were suggested depending on the spectral and magnetic data. The results of density functional theory were applied to illustrate the geometry of L towards the metal ions. Coats–Redfern and Horowitz–Metzger methods were applied to investigate the kinetic and thermodynamic parameters of the chelates. Cyclic voltammetry was carried out to study the stability of the Co2+ and Fe3+ chelates. L and its complexes were tested against three types of cancer cells, antibacterial and antifungal.
- Mostafa, Mohsen M.,Elaskalany, Abdelmonem H.,El-Kkholy, Doaa E.
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- Heavy-atom isotope effects on the hydrazinolysis of methyl formate
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The carbonyl carbon, carbonyl oxygen, and nitrogen nucleophile isotope effects were measured for the hydrazinolysis of methyl formate at pH 8 and 10. At pH 8, where breakdown of a tetrahedral intermediate to products is rate-determining, the carbonyl carbon isotope effect is k12/k13 = 1.038, the carbonyl oxygen isotope effect is k16/k18 = 1.003, and the nitrogen nucleophile isotope effect is k14/k15 = 0.990. The isotope effects at pH 8 are consistent with a late transition state, which greatly resembles the hydrazide product. At pH 10, where formation of a tetrahedral intermediate is rate-determining, the carbonyl carbon isotope effect is k12/k13 = 1.020, the carbonyl oxygen isotope effect is k16/k18 = 1.004, and the nitrogen nucleophile isotope effect is k14/k15 = 0.9917. These isotope effects are best rationalized in terms of a concerted general base catalyzed nucleophilic attack of hydrazine on methyl formate as the rate-determining step.
- Marlier, John F.,Haptonstall, Brandy A.,Johnson, Amanda J.,Sacksteder, Katherine A.
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- Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
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Paragraph 0055-0056; 0070; 0090; 0093
(2021/07/24)
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- Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
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A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
- Liu, Jie,Zhang, Guang-Yu,Zhang, Zhe,Li, Bo,Chai, Fei,Wang, Qi,Zhou, Zi-Dan,Xu, Ling-Ling,Wang, Shou-Kai,Jin, Zhen,Tang, You-Zhi
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- Synthesis method of azaconazole intermediate
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The invention discloses a synthesis method of an azaconazole intermediate. The synthesis method mainly comprises a synthesis method of 2,4-dichloroacetophenone, a synthesis method of 2-bromo-1-(2,4-dichlorophenyl) ethyl ketone, and a synthesis method of ketal. The preparation method has the advantages that the development of the novel azaconazole bactericide fills up a domestic blank in the field,similar derivative synthesis research based on the synthesis method is in the ascendant, and successful development and industrial implementation of various novel bactericides can be realized. The invention provides a novel azaconazole synthesis method.
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Paragraph 0057
(2019/01/04)
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- Process for the Preparation of Triazole Antifungal Drug, Its Intermediates and Polymorphs Thereof
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A process for the preparation of 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one compound of formula-1, its intermediates and polymorphs thereof. (I)
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Paragraph 0335
(2014/12/09)
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- Synthesis and characterization of two formyl 2-tetrazenes
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The synthesis of two formyl 2-tetrazenes, namely, (E)-1-formyl-1,4,4- trimethyl-2-tetrazene (2) and (E)-1,4-diformyl-1,4-dimethyl-2-tetrazene (3), by oxidation of (E)-1,1,4,4-tetramethyl-2-tetrazene (1) using potassium permanganate in acetone solution is presented. Compound 3 was also synthesized in an improved yield from the oxidation of 1-formyl-1-methylhydrazine (4 a) using potassium permanganate in acetone. Both compounds 2 and 3 were characterized by analytical (elemental analysis, GC-MS) and spectroscopic methods (1H, 13C, and 15N NMR spectroscopy, and IR and Raman spectroscopy). In addition, the solid-state structures of the compounds were confirmed by low-temperature X-ray analysis. (Compound 2: triclinic; space group P-1; a=5.997(1) A, b=8.714(1) A, c=13.830(2) A; α=107.35(1)°, β=90.53(1)°, γ=103.33(1)°; VUC=668.9(2) A3; Z=4; ρcalc=1.292 cm-3. Compound 3: monoclinic; space group P21/c; a=5.840(2) A, b=7.414(3) A, c=8.061(2) A; β=100.75(3) °; VUC=342(2) A3; Z=2; ρcalc=1. 396 g cm-3.) The vibrational frequencies of compounds 2 and 3 were calculated using the B3LYP method with a 6-311+G(d,p) basis set. We also computed the natural bond orbital (NBO) charges using the rMP2/aug-cc-pVDZ method and the heats of formation were determined on the basis of their electronic energies. Furthermore, the thermal stabilities of these compounds, as well as their sensitivity towards classical stimuli, were also assessed by differential scanning calorimetry and standard BAM tests, respectively. Lastly, the attempted synthesis of (E)-1,2,3,4-tetraformyl-2-tetrazene (6) is also discussed.
- Delalu, Henri,Sabate, Carlos Miro
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experimental part
p. 715 - 724
(2012/07/03)
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- Synthesis of 1,6-hexanediyl-bis(semicarbazides) and 1,6-hexanediyl-bis(1,2, 4-triazol-5-ones) and their antiproliferative and antimicrobial activity
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A series of 1,6-bis(3-substituted 1,5-dihydro-5-oxo-4H-1,2,4-triazol- -4-yl)hexanes 3a-g were synthesized by the cyclization reaction of 1,6-bis{[(2- -substituted hydrazinyl)carbonyl]amino}hexanes 2a-g in alkaline medium. The new derivatives 3a-c were screened in vitro for their antiproliferative and anticancer activity in human tumor cell lines derived from breast and lung carcinoma cells. Compounds 3a (at a concentration of 0.18 mM), 3b (at concentrations of 0.12 and 0.02 mM) and 3c (at concentrations of 0.23 and 0.11 mM) were found to be the most effective against the lung cell line. Compound 3a had the greatest antiproliferative effect on the breast carcinoma cell line. Representative compounds were established and evaluated as antimicrobial agents. All the tested derivatives showed minimum inhibitory concentrations (MIC) in the range 1.87-7.5 μg mL-1. Compound 3b was the most effective against Candida albicans (MIC 1.87 μg mL-1). Copyright 2012 (CC) SCS.
- Pitucha, Monika,Rzymowska, Jolanta,Olender, Alina,Grzybowska-Szatkowska, Ludmia
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scheme or table
p. 1 - 8
(2012/05/05)
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- Synthesis, experimental and theoretical study on the structure of some semicarbazides with potential antibacterial activity
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A series of 1,4-disubstituted semicarbazide and 4,4'-bis[1-substituted semicarbazide]diphenyl-methane derivatives were synthesized to explore their antibacterial activity. New compounds were characterized by elemental analysis and spectroscopic data. In order to find the tautomeric equilibrium for the molecules energy calculations for each possible tautomeric form of model compound 2, and for the most antibacterially active compound 7 in the investigated series, were calculated for the gas phase at the RHF/SCF/6-31G** level of theory.
- Pitucha, Monika,Karczmarzyk, Zbigniew,Kosikowska, Urszula,Malm, Anna
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scheme or table
p. 505 - 511
(2011/06/28)
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- Synthesis and antihyperlipidemic activity of some novel 4-(substitutedamino)-5-substituted-3-mercapto-(4H)-1,2,4-triazoles
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Hyperlipidemia is considered one of the key factors for cardiovascular diseases. Based on earlier work on a series of 5-alkyl-4-aryl-3-mercapto-(4H)-1, 2,4-triazoles, for further lead modification, a series of 4-(substituted)amino- 5-substituted-3-mercapto-(4H)-1,2,4-triazoles was designed. Target compounds were synthesized by the well known Hoggarth synthesis of substituted 1,2,4-triazoles. Synthesized compounds were screened for lipid lowering activity using the "Poloxamer 407 induced hyperlipidemia in rats" model at a dose of 100 mg/kg p. o. Compounds were found to alter serum lipid levels significantly. Most of the compounds significantly reduced serum cholesterol and triglyceride levels. Some of the compounds were found to reduce triglycerides and elevate high density lipoprotein (HDL) levels more than the standard drug atorvastatin (CAS 134523-03-8). Compounds with chloro substitution on aryl rings were found more active in reducing serum lipid levels than other substitutions. ECV ? Editio Cantor Verlag.
- Chhabria, Mahesh T.,Suhagia, Bhanubhai N.,Brahmkshatriya, Pathik S.,Raval, Priyesha M.
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scheme or table
p. 452 - 457
(2012/06/16)
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- Novel route for the transformation of a pyrimidine ring using hydrazides
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It has been shown from X-ray structural analytical data that the reaction of 2-ethoxycarbonylmethyl-1,4,6-trimethylpyrimidinium iodide with carboxylic acid hydrazides gives pyrazolo[1,5-a]pyrimidine derivatives and not the isomeric triazolo[4,3-a]pyridines previously reported. This novel and previously unreported rearrangement of 1,2-dialkylpyrimidinium salts occurs via recyclization of the pyrimidine ring with inclusion of a fragment of the nucleophilic reagent into the transformation product. 2006 Springer Science+Business Media, Inc.
- Danagulyan,Tadevosyan,Tamazyan,Panosyan
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p. 233 - 245
(2007/10/03)
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- New ditopic and tripodal 1,2,4-triazole- and tetrazole-based ligands for coordination chemistry
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The practical synthesis of two new classes of polytopic azole-based ligands is reported. The synthesis of the precursor amines was achieved by substitution of a leaving group by an azide followed by reduction with triphenylphosphine and water. Another efficient method employs a Mitsunobu coupling with phthalimide allowing the conversion of a primary alcohol into a primary amine. The triazole and tetrazole were obtained by cyclization of these amine precursors. The first family consisted of ditopic ligands containing both 1-R-tetrazole and 4-R-1,2,4-triazole moieties linked by an alkyl spacer, while the second consists of branched ligands with three azole cycles linked to a benzene core through ether bonds. Both classes are suitable for building multidimensional polynuclear coordination assemblies and for the observation of thermal spin state crossover behavior with iron(II) ions. Georg Thieme Verlag Stuttgart.
- Boland, Yves,Hertsens, Pascale,Marchand-Brynaert, Jacqueline,Garcia, Yann
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p. 1504 - 1512
(2007/10/03)
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- NOVEL PROCESSES FOR THE PREPARATION OF SUBSTITUTED PROPENONE DERIVATIVES
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The present invention provides industrial and commercial processes for the preparation of 2-acyl-5-benzylfuran derivatives, 1,2,4-triazole-3-carboxylic acid ester derivatives and propenone derivatives having anti-HIV activities and usuful crystals thereof. wherein R1, R2 and R4 each is independently hydrogen or the like; A is CR6 or N; R6 is hydrogen or the like; Q is a protecting group; and L is a leaving group.
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- New straightforward synthesis and characterization of a unique 1β- methylcarbapenem antibiotic biapenem bearing a σ-symmetric bicyclotriazoliumthio group as the pendant moiety
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Biapenem 1, (1R,5S,6S,)-2-[(6,7-dihydro-5H-pyrazolo[1,2- α][1,2,4]triazolium-6-yl)thio]-6-yl)thio]-6-[(R)-1-hydroxyethyl]-1- methylcarbapen-2-em-3-carboxylate, is a new non-natural 1β-methylcarbapenem antibiotic which exhibits a wide range of antibacterial activity, remarkable chemical stability, and extensive stability against human renal dehydropeptidase-I. Mercaptobicyclotriazolium chloride 2 useful for the pendant moiety of 1 was successfully synthesized starting from hydrazine hydrate 3 along an economically available synthetic route. The thiol 2 was efficiently exploited for an expeditious synthesis of biapenem 1. Characterization (crystal structure, nonbonded S- - -O interaction, conformational analysis, and CH- - -O hydrogen bonds) of 1 was investigated by its X-ray crystallographic, 1H NMR, and deuteration experiment analyses.
- Kumagai, Toshio,Tamai, Satoshi,Abe, Takao,Matsunaga, Hiroshi,Hayashi, Kazuhiko,Kishi, Ikuo,Shiro, Motoo,Nagao, Yoshimitsu
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p. 8145 - 8149
(2007/10/03)
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- Clarifiers for polyolefins and polyolefin compositions containing same
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Dibenzylidene xylonates are a new class of clarifiers for polyolefins. The invention includes polyolefin compositions having the new clarifiers therein.
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- Amidrazones and derivatives thereof
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The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging) which contain novel amidrazones and derivatives thereof. Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
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- 3,6,7,8-Substituted-s-triazolo[4,3-b]pyridazines as bronchodilators
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3,6,7,8-Substituted-s-triazolo-pyridazine compounds such as 7,8-dimethyl-6-morpholino-3-methyl-s-triazolo[4,3-b]pyridazine or 7,8-dimethyl-6-(1-pyrrolidinyl)-3-(isopropyl)-s-triazolo-[4,3-b]pyridazine are prepared by the reaction of a carboxylic acid with a substituted 3-hydrazino-6-halo-pyridazine followed by the reaction of the resulting 6-halotriazolopyridazine with a corresponding base. The compounds have pharmacological activity as bronchodilators.
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- Benzofuro[3,2-c]pyrazol-3-amine derivatives
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Herein is disclosed benzofuro[3,2-c]pyrazol-3-amine derivatives, therapeutically acceptable acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions. The derivatives are useful for producing analgesia in a mammal. In addition, some of the derivatives are useful for inhibiting gastric acid secretion, convulsions, anxiety and aggression, and producing muscle relaxation, hypnosis and sedation in a mammal.
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- Purification and characterization of animal porphobilinogen synthases. I. Bovine liver porphobilinogen synthase
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Porphobilinogen synthase was purified from ox liver by ammonium sulfate fractionation, heat denaturation and column chromatography (purification: 400-fold; specific activity 4.72 nkat). The molecular weight of the native enzyme obtained by thin-layer gel filtration is about 280 000. Using 8M urea in the presence of dithiothreitol as reducing agent, the molecule breaks down into 8 subunits of molecular weight 36 000 (dodecyl-sulfate gel electrophoresis); the preparation of aminoethylated subunit is described. According to the above-mentioned molecular weight and to the quantitative amino acid analysis after total hydrolysis, the following composition of the enzyme sbunit was calculated Asx23-24 Thr7 Ser23-24 Glx29-31 Pro22-23 Gly22-24 Ala36-37 Val23-26 Met7 Ile9 Leu34-35 Tyr10 Phe11-12 Lys11-12 Cys6-7 His6-8 Arg22 Trp1-2. The subunits, having two free sulfhydryl groups, therefore consist of a chain of about 306 amino acids. The Dansyl-Edman procedure did not enable identification of any free N-terminal amino acid. The acyl group blocking the N-terminus is an acetyl group. It was identified, after hydrazinolysis of the enzyme, by means of chromatographic comparison with 1-formyl-2-dansyl-hydrazine and 1-acetyl-2-dansylhydrazine, whose syntheses and UV spectra are described.
- Kreutzer,Schmidt,Stadler,Zeitler
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p. 1081 - 1091
(2007/10/05)
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