- 1,2,4-TRIAZOLINOE CB1 INHIBITORS
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Disclosed are compounds according to Formula (I), and related pharmaceutical compositions. Also disclosed are therapeutic methods, e.g., of treating diseases such as diabetic kidney disease, diabetic nephropathy, obesity-related kidney disease, focal segmental glomerular sclerosis, IgA nephropathy, nephrotic syndrome, kidney fibrosis, Prader Willi syndrome, metabolic syndrome, gastrointestinal diseases, non-alcoholic liver disease, alcoholic liver disease, or non-alcoholic fatty liver disease, using the compounds of Formula (I).
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Page/Page column 56-57; 49
(2021/09/11)
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- PIPERAZINE CYCLIC UREAS
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Provided are piperazine cyclic urea compounds that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), pharmaceutically acceptable salts, hydrates and stereoisomers thereof. Provided are also pharmaceutical compositions, methods of making, and methods of use which include treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.
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Paragraph 0124
(2021/11/26)
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- 1-(N,N-DISUBSTITUTED CARBAMOYL) 4-(SUBSTITUTED SULFONYL)TRIAZOLIN-5-ONE DERIVATIVE, 4-(N,N-DISUBSTITUTED CARBAMOYL) 1-(SUBSTITUTED SULFONYL)TRIAZOLIN-5-ONE DERIVATIVE, AND HERBICIDE CONTAINING SAID DERIVATIVE AS ACTIVE INGREDIENT
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The present invention provides 1-(N,N-disubstituted carbamoyl) 4-(substituted sulfonyl)triazolin-5-one derivatives represented general formula 1, and 4-(N,N-disubstituted carbamoyl) 1-(substituted sulfonyl)triazolin-5-one derivatives represented by general formula (11), which show excellent herbicidal activity, and herbicides characterized by containing the derivatives as an active ingredient. In general formula (1), R1-R4 represent predetermined substituents. In general formula (11), R11-R14 represent predetermined substituents.
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Paragraph 0224; 0225; 0226; 0237; 0238; 0239
(2020/12/08)
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- Structure-activity relationships of triazole-benzodioxine inhibitors of cathepsin X
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Cathepsin X is a cysteine carboxypeptidase that is involved in various physiological and pathological processes. In particular, highly elevated expression and activity of cathepsin X has been observed in cancers and neurodegenerative diseases. Previously, we identified compound Z9 (1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-one) as a potent and specific reversible cathepsin X inhibitor. Here, we have explored the effects of chemical variations to Z9 of either benzodioxine or triazol moieties, and the importance of the central ketomethylenethio linker. The ketomethylenethio linker was crucial for cathepsin X inhibition, whereas changes of the triazole heterocycle did not alter the inhibitory potencies to a greater extent. Replacement of benzodioxine moiety with substituted benzenes reduced cathepsin X inhibition. Overall, several synthesized compounds showed similar or improved inhibitory potencies against cathepsin X compared to Z9, with IC50 values of 7.1 μM–13.6 μM. Additionally, 25 inhibited prostate cancer cell migration by 21%, which is under the control of cathepsin X.
- Fonovi?, Ur?a Pe?ar,Gobec, Stanislav,Hrast, Martina,Knez, Damijan,Kos, Janko,Proj, Matic,Zidar, Nace
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- METHOD FOR OBTAINING SOLUTIONS OF OTA IN A CONCENTRATED SULFURIC ACID MEDIUM; SAID SOLUTIONS; AND METHOD FOR PREPARING ONTA
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A method for obtaining solutions that contain 1,2,4-triazole-5-one (OTA) in concentrated sulphuric acid, includes using 3-amino-1,2,4-triazole (ATA) as a precursor of OTA. There is also provided a method for preparing 3-nitro-1,2,4-triazole-5-one (4) (ONTA) from the solutions.
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Paragraph 0108; 0109; 0110; 0111
(2016/03/13)
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- METHOD FOR OBTAINING SOLUTIONS OF OTA IN A CONCENTRATED SULFURIC ACID MEDIUM; SAID SOLUTIONS; AND METHOD FOR PREPARING ONTA
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A method for obtaining solutions that contain 1,2,4-triazole-5-one (OTA) in concentrated sulphuric acid, includes using 3-amino-1,2,4-triazole (ATA) as a precursor of OTA. There is also provided a method for preparing 3-nitro-1,2,4-triazole-5-one (4) (ONTA) from the solutions.
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Paragraph 0092 - 0098
(2017/01/09)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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- The crystal and computed structures of 1,2,4-triazol-5-one (TO)
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1,2,4-Triazol-5-one (TO) was synthesized by reacting semicarbazide hydrochloride with formic acid and its single crystal was grown by the slow evaporation method. Its molecular structure and crystal structure were determined by X-ray single crystal diffraction technique. The obtained results show that the crystal belongs to Crystal system of Monoclinic, space group Pn. It was characterized by elemental microanalysis and FT-IR techniques. Based on the crystal data, we had also carried quantum chemistry calculations on the title compound using the B3LYP and MP2 method with cc-pVTZ basis set. The calculation results further demonstrate the crystal structure of title compound and its other related properties.
- Zhang, Jianguo,Zhang, Tonglai,Ma, Guixia,Yu, Kaibei
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p. 503 - 508
(2007/10/03)
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- Regioselective synthesis of 1,2,4-triazol-3(2H)-ones and their 3(2H)-thiones: Kinetic studies and selective pyrolytic deprotection
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Selective pyrolytic deprotection of 2-ethyl and 2-cyanoethyl-4-arylidenimino-1,2,4-triazol-3(2H)-ones and their 3(2H)-thiones was studied by flash vacuum pyrolysis. This study is useful in regioselective synthesis of 2-and 4-substituted 1,2,4-triazoles of potential biological applications. The kinetic results and product analysis lend support to a reaction pathway involving a six-membered transition state.
- Al-Awadi, Nouria A.,Ibrahim, Yehia A.,Kaul, Kamini,Dib, Hicham
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- Process for the preparation of 1,2,4- triazolin-5-one derivatives
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The present invention relates to a process for the preparation of a compound of formula (I) wherein R represents hydrogen, C1-10alkyl, haloC1-10alkyl or aryl; which are useful intermediates in the preparation of morpholine derivatives of formula (A). Compounds of formula (A) are useful as therapeutic agents.
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- Ribofuranosyl triazolone: A natural product herbicide with activity on adenylosuccinate synthetase following phosphorylation
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2,4-Dihydro-4-(β-D-ribofuranosyl)-1,2,4(3H)-triazol-3-one (2) was identified as the principal phytotoxic component of a fermentation broth derived from an Actinomadura. The compound is a new natural product, but known by synthesis. Bread-spectrum herbicidal activity was demonstrated in greenhouse tests. Metabolite reversal studies suggested the target site was adenylosuccinate synthetase, which was confirmed by direct measurement of the activity of the 5'-phosphorylated derivative on the isolated enzyme.
- Schmitzer, Paul R.,Graupner, Paul R.,Chapin, Eleanor L.,Fields, Steven C.,Gilbert, Jeff R.,Gray, Jim A.,Peacock, Cathy L.,Gerwick, B. Clifford
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p. 777 - 781
(2007/10/03)
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- Synthesis of [3-14C]- and [5-14C]-labelled 5-nitro-1,2,4-triazol-3-one (NTO) and study of its chemical decomposition
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The chemical decomposition of NTO 1 and its corresponding amine ATO 2 was investigated. To make easier the identification of the decomposition products, we synthesized 14C-labelled NTO and ATO. Our results confirmed the high stability of the NTO triazolone ring. Its scission can be achieved partially by sulfuric acid under intensive heat and pressure. The triazolone ring of ATO was cleaved in alkaline solution. Carbon dioxide is evolved leaving a polar compound assumed to be aminoguanidine. The deamination of ATO was achieved by nitrosation. In dilute HCl (0.15 N), 2 equivalents of NO2- led to the triazolone 4, through a radical de-diazotation of the diazo intermediate. With 3 to 10 equivalents of NO2-, the nitrosation leads exclusively to the azide 6.
- Le Campion,De Suzzoni-Dezard,Robic,Vandais,Varenne,Noel,Ouazzani
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p. 1203 - 1213
(2007/10/03)
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- Synthesis and thermal decomposition of 15N-labelled NTO
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5-Nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (NTO) has been synthesized in good yield with 15N at the 1 and 2 positions. The N-H coupling provides unequivocal assignments for 1H and 15N NMR spectra and the acidic proton. The products of thermal decomposition at 270 °C were identified spectroscopically. NMR spectra reveal that thermal decomposition results in the formation of 2,4-dihydro-3H-1,2,4-triazol-3-one and ammonia (the latter observed as ammonium ion). The production of ammonia from the thermal decomposition of an energetic material is unprecedented. The gas products HCN, 15N14N, 15N2 and CO were detected by mass spectrometry. Some possible mechanisms of thermal decomposition are discussed.
- Fan, Leimin,Dass, Chhabil,Burkey, Theodore J.
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- Theoretical and experimental studies of the structure and vibrational spectra of NTO
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The structure and vibrational spectra of the high explosive 5-nitro- 2,4-dihydro-3H-1,2,4-triazol-3-one (NTO) have been determined by ab initio molecular orbital calculations at the Hartree-Fock and second-order Moller- Plesset levels and by density functional theory (B3LYP). Experimental frequencies for the molecule have been determined from infrared spectra of pure NTO films and NTO molecules isolated in an argon matrix at 21 K. A force field for gas phase NTO has been obtained based on calculated results at the MP2/6-311G** level. In addition, a force field for solid state NTO has been constructed using the experimental vibrational frequencies for NTO films and scaled ab initio vibrational frequencies. Differences between the solid state and gas phase results indicate that the environment and preparation procedure exert a marked influence on the spectral characteristics of the NTO molecule.
- Sorescu, Dan C.,Sutton, Teressa R.L.,Thompson, Donald L.,Beardall, David,Wight, Charles A.
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- Preparation and 13C NMR Spectra of Some Azolones, Azolothiones and Their Methoxy and Methylmercapto Relatives
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13C NMR chemical shifts are reported for the title compounds.The use of these data for investigating potential equilibria between azolones and azolothiones on the one hand and methoxy and methylmercaptoazoles on the other, is discussed.It is concluded that only qualitatively reliable estimates of the position of equilibrium are available.
- Bojarska-Olejnik, Elzbieta,Stefaniak, Lech,Witanowski, Michal,Webb, Graham A.
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p. 295 - 303
(2007/10/02)
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- Syntheses and Structure Assignments of Six Azolinone Ribonucleosides
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N-Ribosidation of a series of azolinones was achieved via silylation and SnCl4 catalysis.N-Ribosidation of 4-imidazolin-2-one gave 1-β-D-ribofuranosyl-4-imidazolin-2-one; of 1,2,4-triazolin-3-one gave 2- and 4-β-D-ribofuranosyl-1,2,4-triazolin-3-one, and 2,4-di-β-D-ribofuranosyl-1,2,4-triazolin-3-one; and of 2-tetrazolin-5-one gave 1-β-D-ribofuranosyl-2-tetrazolin-5-one and 1,4-di-β-D-ribofuranosyl-2-tetrazolin-5-one.Structure assignments were based on NMR and mass spectra, microanalytical data, and interconversions.The triazolinone monoriboside isomer structures were differentiated by 13C NMR long-range coupling patterns, and the assignments were confirmed by X-ray crystallography.New syntheses were developed for several of the ribonucleosides by fashioning the azolinone rings from 2,3,5-tri-O-benzoylribofuranosyl isocyanate.
- Haines, David R.,Leonard, Nelson J.,Wiemer, David F.
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p. 474 - 482
(2007/10/02)
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- ACETALS OF LACTAMS AND ACID AMIDES. 37. * REACTIONS OF AMIDE AND LACTAM ACETALS WITH DERIVATIVES OF UREA AND URETHANE AND SYNTHESIS OF CONDENSED PYRIMIDINES
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The reactions of diethylacetals of dimethylacetamide and N-methylbutyro-, -valero-, and -caprolactams with urea, thiourea, and urethane lead to the corresponding N-carbamide- and N-ethoxycarbonylamides, on the basis of which derivatives of pyrimidine and pyrrolo- and pyridopyrimidine and pyridoazepine, as well as triazole derivatives, were synthetized.
- Kaimanakova, S. I.,Kuleshova, E. F.,Solov'eva, N. P.,Granik, V. G.
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p. 1208 - 1211
(2007/10/02)
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