- Molecular structure, vibrational spectra and photochemistry of 5-mercapto-1-methyltetrazole
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In this work, 5-mercapto-1-methyltetrazole was studied by low temperature matrix-isolation and solid-state infrared spectroscopy, DFT(B3LYP)/6-311++G(d,p) calculations and photochemical methods. In the low temperature neat solid phase and isolated in an argon matrix, the compound was found to exist in the 1-methyl-1,4-dihydro-5H-tetrazole-5-thione tautomeric form. The infrared spectra of the compound were fully assigned and correlated with structural properties. In situ UV-irradiation (λ > 235 nm) of the matrix-isolated monomer is shown to induce different photochemical processes, all of them involving cleavage of the tetrazole ring: e. g. (1) molecular nitrogen expulsion, with production of 1-methyl-1H-diazirene-3-thiol, which is produced in two different conformers; (2) ring cleavage leading to production of methyl isothiocyanate and azide; (3) simultaneous elimination of nitrogen and sulfur with production of N-methylcarbodiimide. Following these photoprocesses, subsequent reactions occur, leading to production of methyl diazene, carbon monosulphide and nitrogen hydride. Spectroscopic evidence of the production of the above-mentioned chemical species is provided.
- Gomez-Zavaglia, A.,Reva, I. D.,Frija, L.,Cristiano, M. L.,Fausto, R.
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Read Online
- Discovery of quinazoline derivatives as a novel class of potent and in vivo efficacious LSD1 inhibitors by drug repurposing
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Histone lysine-specific demethylase 1 (LSD1) is an important epigenetic modulator, and is implicated in malignant transformation and tumor pathogenesis in different ways. Therefore, the inhibition of LSD1 provides an attractive therapeutic target for cancer therapy. Based on drug repurposing strategy, we screened our in-house chemical library toward LSD1, and found that the EGFR inhibitor erlotinib, an FDA-approved drug for lung cancer, possessed low potency against LSD1 (IC50 = 35.80 μM). Herein, we report our further medicinal chemistry effort to obtain a highly water-soluble erlotinib analog 5k (>100 mg/mL) with significantly enhanced inhibitory activity against LSD1 (IC50 = 0.69 μM) as well as higher specificity. In MGC-803 cells, 5k suppressed the demethylation of LSD1, indicating its cellular activity against the enzyme. In addition, 5k had a remarkable capacity to inhibit colony formation, suppress migration and induce apoptosis of MGC803 cells. Furthermore, in MGC-803 xenograft mouse model, 5k treatment resulted in significant reduction in tumor size by 81.6% and 96.1% at dosages of 40 and 80 mg/kg/d, respectively. Our findings indicate that erlotinib-based analogs provide a novel structural set of LSD1 inhibitors with potential for further investigation, and may serve as novel candidates for the treatment of LSD1-overexpressing cancers.
- Li, Zhonghua,Li, Zhongrui,Ma, Jinlian,Miao, Jinxin,Qin, Tingting,Yang, Nian,Zhang, Xinhui,Zhang, Zhenqiang,Zhao, Taoqian,Zhao, Xuan
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- Double three bromo 1,3-di-pyridine salt-based propane and its preparation method, method of use, recovery method and application
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The invention discloses a double tribromo 1,3-bipyridine onium salt dimethylmethane, and a preparation method, an application method, a recovery method and application thereof. The preparation method comprises the following steps: dissolving 1,3-bipyridine onium salt dimethylmethane by using water, and then adding potassium bromide; adding potassium peroxymonosulfate sulfate compound brine solution to prepare a clear solution after dissolving potassium bromide, and then stirring and reacting at -10 to 0 DEG C until solid is separated out; separating out solid, so as to obtain the double tribromo 1,3-bipyridine onium salt dimethylmethane. The product can be used for preparing isothiocyanate, aromatic thiourea or acetanilide. The preparation method disclosed by the invention is mild in condition, and simple to operate the reaction process, and raw materials are easily available. The double tribromo 1,3-bipyridine onium salt dimethylmethane not only can be used as a brominating reagent, but also can be used as organic synthesis intermediates, meanwhile, the reaction efficiency is improved, and the double tribromo 1,3-bipyridine onium salt dimethylmethane is convenient to recover and can be recycled.
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Paragraph 0075; 0076; 0185; 0186
(2016/10/07)
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- Method And Apparatus For The Enhancement Of The Biocidal Efficacy Of Monoalkyldithiocarbamate Salts
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The present invention provides a method of treating an aqueous system for biocide control, by adding an acidified solution that includes monoalkyldithiocarbamate salt and alkyl isothiocyanate to an aqueous system. A biocide feed system is also provided that is configured to generate a reproducible level of alkyl isothiocyanate. The method and system provide effective levels of alkyl isothiocyanate for rapid biocidal activity, along with levels of monoalkyldithiocarbamate salt which can decompose to form additional alkyl isothiocyanate and provide longer-term biocidal activity.
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Paragraph 0051; 0052
(2014/04/03)
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- Synthesis and structure-activity relationships of aliphatic isothiocyanate analogs as antibiotic agents
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Isothiocyanates (ITCs) are one of the many classes of breakdown products of glucosinolates found in plants and exhibit biologic activity against various pathogens. In this work, aliphatic isothiocyanates were prepared and the antimicrobial activities against plant pathogenic fungi and bacteria were tested to understand the structure-activity relationships. The results indicated that longer-chain derivatives exert a steric inhibition on toxicity of ITCs against Rhizoctonia solani because of steric hindrance and the order of the eight aliphatic ITCs was ethyl > n-propyl > methyl > n-hexyl > n-octyl > n-butyl > n-heptyl > n-pentyl. Because the hydrophobicity of ITCs was enhanced by increasing alkyl chain length, the antibacterial activity of ITCs against Erwinia carotovora was moderately intense with an increase in hydrophobicity and the order was n-octyl > n-pentyl > n-heptyl > n-hexyl > n-propyl > n-butyl > methyl > ethyl. The present study revealed that some of the compounds exhibited promising antimicrobial activity and could be used as an acceptable alternative to the traditional synthetic fungicides for controlling R. solani and E. carotovora.
- Li, Deguang,Shu, Yanan,Li, Pingliang,Zhang, Wenbing,Ni, Hanwen,Cao, Yongsong
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p. 3119 - 3125
(2013/07/11)
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- METHODS OF USING DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY (ADP-RIBOSE)POLYMERASE (PARP)
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Provided herein are methods of treating cancer comprising administering a topoisomerase inhibitor, temozolomide, or a platin in combination with a Compound of Formula (I) or Formula (II), where the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein.
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Page/Page column 154
(2011/11/01)
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- HL005 - A new selective PPARγ antagonist specifically inhibits the proliferation of MCF-7
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Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear transcription factor which is involved in many diseases, such as diabetes, inflammation, dyslipidemia, hypertension, and cancer. Recently, there are many reports showing that PPARγ agonists have preclinical and clinical anticancer activity, with relatively few reports on anticancer effects of PPARγ antagonists. From our compound library, a novel 3-thiazolinone- modified benzoic acid derivative HL005 is found as PPARγ selective ligand through SPR analysis (KD = 0.21 μM), yeast two-hybrid results suggest that HL005 antagonize the potent PPARγ agonist rosiglitazone-induced recruitment of the coactivator for PPARγ (IC 50 = 7.97 μM). Different from the most reported PPARγ antagonist, HL005 can inhibit the proliferation of MCF-7 cell line in a concentration-dependent manner and induce cell cycle arrest at G2/M phase, other than interference with cell adhesion. In order to study the binding mode of this compound, three derivatives are synthesized to get more detail about the structure-activity relationship, molecular docking and the NMR spectra indicate that similar to most PPARγ ligand, the carboxylic acid group is an important moiety for HL005 and contributes strong interaction with PPARγ.
- Lu, Weiqiang,Che, Peng,Zhang, Yanyan,Li, Honglin,Zou, Shien,Zhu, Jin,Deng, Jing,Shen, Xu,Jiang, Hualiang,Li, Jian,Huang, Jin
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experimental part
p. 112 - 120
(2012/03/10)
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- DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)
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A compound having the structure set forth in Formula (I) and Formula (II): wherein the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.
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Page/Page column 80
(2010/03/02)
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- Alkoxy isothiocyanates as intermediates in the flash vacuum pyrolysis of alkoxythioureas
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Methoxy isothiocyanate MeONCS 2b was detected by matrix isolation IR spectroscopy following flash vacuum pyrolysis (FVP) of N-methoxythioureas, N-tert-butyl-N′-methoxythiourea 1d being the best precursor. Isothiocyanates 3, amines, and aldehydes are also
- Pedersen, Carl Th.,Jensen, Frank,Flammang, Robert
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experimental part
p. 69 - 74
(2009/07/18)
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- A facile and new approach to synthesize 2-amino-4-(4-amoinophenyl)-1H-1,3- diazol-1-yl-alkylaminomethanethiones
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An "intellectual connection" approach to design a facile and new synthesis of suitably substituted 2-aminoimidazole-based precursors of expected anti-asthmatic agents through a benzidine type of rearrangement of 2-phenylazoimidazole and subsequent coupling of the product thus obtained with alkylisothiocyanates involving a degenerative operation, thereby improving the time frame of the overall synthetic sequence, is reported. The alkylisothiocyanates required in this synthetic sequence are prepared using a best combination of reported methods. The compounds reported here can be used to produce derivatives of other biological agents. Birkhaeuser 2007.
- Verma, Raman K.,Aggarwal, Monika,Bansal, Manisha,Kaur, Inder Preet
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p. 483 - 491
(2008/04/01)
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- Benzothiazole derivatives with activity as adenosine receptor ligands
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The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
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- Substituted pyrrolopyrimidines and processes for their preparation
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There are described 7H-pyrrolo[2,3-d]pyrimidine derivatives of the formula I in which the substituents are as defined in claim 1. These compounds inhibit the tyrosine kinase activity of the receptor for the epidermal growth factor (EGF) and c-erbB2 kinase and can be used as anti-tumor agents.
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- A marvelous catalysis of tellurium in the formation of isothiocyanates from isocyanides and sulfur
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Catalytic activity of tellurium in the formation of isothiocyanates from isocyanides and sulfur has been found to be extremely high and far superior to that of selenium.
- Fujiwara, Shin-Ichi,Shin-Ike, Tsutomu,Okada, Kazuhiro,Aoki, Minoru,Kambe, Nobuaki,Sonoda, Noboru
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p. 7021 - 7024
(2007/10/02)
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- Novel selenium catalyzed synthesis of isothiocyanates from isocyanides and elemental sulfur
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A variety of aliphatic and aromatic isothiocyanates were synthesized in good to excellent yields from corresponding isocyanides and elemental sulfur under mild conditions by use of catalytic amounts of elemental selenium.
- Fujiwara, Shin-Ichi,Shin-Ike, Tsutomu,Sonoda, Noboru,Aoki, Minoru,Okada, Kazuhiro,Miyoshi, Noritaka,Kambe, Nobuaki
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p. 3503 - 3506
(2007/10/02)
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- Oxidation of mixtures of thioureas: Part XI - Oxidation of mixtures of 1-alkyl-3-arylthioureas and thiourea and study of steric influence around aryl groups on formation of 1,2,4-thiadiazolines
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Hydrogen peroxide oxidation of a mixture of 1-alkyl-3-arylthiourea and thiourea in acidic alcoholic solution yields two isomeric 3-amino-1,2,4-thiadiazolines (VI and VII) via amidinothiourea.The rearrangement of the intermediate bis(formamidine)sulphide to the amidinothiourea derivative has been found to be governed by the steric effect.
- Joshua, C P,Sujatha, T S
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p. 600 - 603
(2007/10/02)
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- Synthesis of isothiocyanates by reaction of amides with carbon disulfide in the presence of solid potassium carbonate/sodium hydroxide mixture
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Readily available N-monosubstituted trifluoroacetamides are transformed into isothiocyanates in good yield by reaction, at room temperature, with carbon disulfide in acetonitrile in the presence of anhydrous sodium hydroxide/potassium carbonate basic mixture.
- Albanese,Penso
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p. 1001 - 1002
(2007/10/02)
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- Gas- Phase Ion Chemistry of Siloxide and Silamide Ions by Using the Flowing Afterglow. Unusual Rearrangements Involving SiO and SiS Bond Formation
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Siloxide ions undergo O/S exchange reactions with suitable sulfur-containing neutrals, e.g.H3SiO- + CS2 -> H3SiS- + COS.Silamide ions similarly undergo NR/O and NR/S exchange reactions together with nucleophilic displacement reactions, e.g.: .No simple correlation between rate and mechanism is observed for all the studied reactions.
- O'Hair, Richard A.J.,Sheldon, John C.,Bowie, John H.,Damrauer, Robert,DePuy, Charles H.
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p. 489 - 496
(2007/10/02)
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- REACTION OF α, β-UNSATURATED ACYL ISOTHIOCYANATES WITH SALTS OF DITHIOCARBAMIC ACIDS
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The reaction of unsaturated isothiocyanates with the sodium and calcium salts of N-alkyl- and N,N-dialkyldithiocarbamic acids was studied.Depending on the structure of the dithiocarbamate, the reaction products are thiazines or acyl dithiocarbamates.For the salts of methyldithiocarbamic acid the effect of the concentration and the nature of the metal on the relative yields of 6-phenyl-3-methylpropiorhodanine and 6-phenylpropiorhodanine was studied.A method is proposed for the synthesis of 3-substituted propiorhodanines.
- Krus, K.,Masias, A.,Beletskaya, I. P.
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p. 1421 - 1425
(2007/10/02)
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- Gas-phase Pyrolysis of Methyl Dimethylcarbamate and the Correponding Mono- and Dithio Analogs
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Gas-phase pyrolysis of methyl dimethylcarbamate (1), O-methyl dimethylthiocarbamate (2), S-methyl dimethylthiocarbamate (3), and methyl dimethyldithiocarbamate (4) has been carried out in the temperature range 1043-1404 K applying the gas-phase Curie-point pyrolysis technique.Real-time analysis of the pyrolyses were carried out by field ionization- and collision activation mass spectrometry. 1 and 4 were found to be thermally very stable even after pyrolysis at 1404 K.N-Methyl methanimine was found in moderate yield following pyrolysis of 2 and 3.The possible isomerization of the ester functions were studied by application of collision activation mass spectrometry in combination with 18O and 34S labeling.The results are discussed considering available data on the simple acetic acid esters with special emphasis on the effect of increasing sulfur content.
- Carlsen, Lars,Egsgaard, Helge
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p. 987 - 990
(2007/10/02)
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- Process for production of isothiocyanates
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Isothiocyanates are formed by oxidizing, with gaseous oxygen or air, in the presence of a metal oxidation catalyst a dithiocarbamate with appropriate control of the pH of the reaction medium to suppress the formation of by-products. Optionally a quaternary ammonium halide catalyst can be used to increase product yield.
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- Gas-Phase Synthesis and Reactions of Nitrogen- and Sulfur-Containing Anions
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The flowing afterglow and selected ion-flow tube techniques have been used to study the reactions of H2N- with N2O, CO2, CS2, SO2, and OCS in the gas phase.Thermal energy rate coefficients and product branching ratios have been determined and are discussed in terms of detailed reaction mechanisms.With use of the SIFT-drift technique, the product distribution for the reaction of H2N- with N2O was measured as a function of the center of mass kinetic energy in the range of thermal energy to ca. 15 kcal mol1-.Qualitative studies were made of the reactions of HO-, CH3O-, and (CH3)2N- with N2O, CO2, CS2, SO2, and OCS, and the reactions of a variety of other ions with OCS were also examined.These reactions provide efficient synthetic routes for the gas-phase preparation of a variety of interesting negative ions containing nitrogen and sulfur.The basicities and heats of formation of three of these anions, H2NS-, NSO-, and NCS-, have been bracketed by proton-transfer reactions.The nucleophilicities of these three anions, as well as of H2N-, HO-, HO2-, F-, HS-, CN-, NCO-, N3-, Cl-, and Br- toward CH3I, have been measured.
- Bierbaum, Veronica M.,Grabowski, Joseph J.,DePuy, Charles H.
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p. 1389 - 1393
(2007/10/02)
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- COMPARISON OF THE THERMAL AND MASS-SPECTROMETRIC FRAGMENTATION OF 2,4-THIOXO(OXO)DIHYDRO-5,6-BENZO-1,3-THIAZINES
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The pyrolysis of a series of phenyl- and methyl-substituted 2,4-thioxo(oxo)dihydro-5,6-benzo-1,3-thiazines at the Curie point was studied.Processes involving retrodiene fragmentation with the formation of, respectively, phenyisothiocyanate or phenylisocyanate lie at the foundation of the thermal transformations of these compounds.Among other stable pyrolysis products, aniline, benzonitrile, and benzene were identified by gas chromatography and mass spectrometry.Pyrolysis directly in the mass spectrometer gives a larger number of fragmentation products, since it makes it possible to also record compounds with low stabilities.The results of the two methods of analysis correlate well with one another.
- Stach, I.,Herzschuh, R.,Leistner, S.,Wagner, H.
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p. 265 - 268
(2007/10/02)
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- Reactivite de cyclo- et tri-germazanes: Mise en evidence de la participation de germyleneamines dans des reactions d'insertion-elimination
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Cyclogermazanes (R2GeNR')n (n=2,3), oligomers of germyleneamines, R2Ge=NR', are obtained through aminolysis or amonolysis of Ge-Cl bonds, by intramolecular transamination, or by reaction between chlorogermanes and dilithium amides.The oligomerization degree (n=2,3) is strongly dependent on the nature of the substituents bonded to nitrogen or germanium.Cleavage reactions by bifunctional protic reagents such as diols, dithiols, aminoalcohols, aminothiols and aminoacids have been studied and lead to the corresponding five-membered germa heterocycles resulting from the cleavage of two consecutive Ge-N bonds.Insertion reactions of either heterocumulenes and insaturated dipoles such as RNCO, RNCS, CO2, CS2, PhCHO or oxirane lead to ring expansion.Compounds resulting from diaddition of isocyanates and isothiocyanates to cyclogermazanes, decompose with formation transient germyleneamines which have been characterized by means of their 1,2-cycloaddition reactions with iso- or isothio-cyanates leading to unsatble diazagermetidiones, (or thiones).Similarly, adducts between cyclogermazanes and aldehydes , CO2, CS2 lead to cyclogermoxanes or cyclogermathianes through the corresponding germanones or germathiones. 1,3-Dipoles such as nitrones react with with cyclogermazanes at temperatures around 150 degree C to give unstable 1,3,5,2-oxadiazagermolidines.The reactivity of cyclogermazanes is enhanced in the presence of triethylamine or hexamethylphosphotriamide.The possibility of participation in the latter reactions for the monomeric germyleneamine R2Ge=NR' resulting from the equilibrium cyclogermazane germyleneamine is discussed.
- Lacrampe, G.,Lavayssiere, H.,Riviere-Baudet, M.,Satge, J.
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- A Method for the Simultaneous Preparation of Alkyl Isothiocyanates and Thiols
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Aus primaeren Alkylaminen wurden Ethyl-, Butyl-, Isobutyl- und n-Dodecyldithiocarbamate 2 hergestellt.Letztere lassen sich leicht zu den Isothiocyanaten 3 und Thiolen 4 pyrolisieren.Die Massenspektren der Ester sowie deren Pyrolyseprodukte wurden gemessen.
- Blotny, Grzegorz
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p. 1927 - 1932
(2007/10/02)
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- Relative Bond Dissociation Energies for Two-Ligand Complexes of Cu+ with Organic Molecules in the Gas Phase
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Ralative two-ligand dissociation enthalpies, δD(Cu+-2L), for Cu+ with 43 organic molecules are determined.A pulsed-laser volatilization/ionization sourse is used to generate Cu+ which reacts with EtCl and/or other molecules to give Cu(ligand)2+ species.Equilibrium constants are measured for the ligand-exchange reactions which occur when pairs of ligand molecules are present.Free energies for two-ligand exchange are obtained from the equilibrium constant for the reaction Cu(A)2+ + 2B ->/+ + 2A.The free-energiy differences are added to give a scale of relative free energies for ligand exchange.These are converted to enthalpies to give δD(Cu+-2L) scale with the assumption that enthropy changes are small and can be neglected except for symmetry corrections which are made in appropriate cases.Dependence of δD(Cu+-2L) on functional group and substituent effects is analyzed.These results for Cu+ are compared to available results for other reference acids: H+, Al+, Mn+, Li+, and CpNi+.These comparisons show that Cu+ is a softer acid than the other reference acids.This is apparent from the relative preference of Cu+ for mercaptans and HCN compared to alcohols and other oxygen bases.
- Jones, Roger W.,Staley, Ralph H.
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p. 2296 - 2300
(2007/10/02)
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- Process for the production of isothiocyanates
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Isothiocyanates of the formula (I) in which R is a straight or branched alkyl group with 1 to 18 carbon atoms, preferably methyl, and wherein the alkyl group can be substituted once or more by --OH, --OR1 or --SR1 and where R1 is an alkyl group of 1 to 6 carbon atoms or R is cycloalkyl with 3 to 8 carbon atoms, benzyl or phenyl in which the aromatic nucleus can be substituted once or more by a chlorine atom, a bromine atom, a hydroxyl group, or --R1, --OR1 or --SR1 or R is a pyridyl or thiazolyl group prepared by reacting (1) a dithiocarbamate of the general formula (II) STR1 where R is as defined above and Me is an alkali atom, one valence of an alkaline earth metal atom or the ammonium group whose hydrogen atoms can be substituted by R with (2) a cyanogen halide, preferably cyanogen chloride, in the presence of water. There is employed one mole of a dithiocarbamate of formula II as a 5 to 50 weight % aqueous solution in the presence of an inert organic solvent which is not miscible with water, and preferably in the presence of a base at a temperature from about -10° C to about +50° C, preferably between 0° C and 25° C. There is employed at least one mole of cyanogen chloride per mole of dithiocarbamate. The isothiocyanate produced is isolated from the organic phase.
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