- Fluorescence detection of iodide anion using a donor-acceptor (D-A) thiourea derivative
-
1-(4-acetyl-phenyl)-3-(4-N,N-dimethylaminophenyl)-thiourea is synthesized and characterized by NMR, IR, MS and elemental analysis. The probe exhibits the "turn-off" fluorescence response to iodide anion in THF/H2O (v/v = 9/1) pH = 7.4 Tris-HCl buffer solution, which is attributed to the intramolecular charge transfer (ICT). It is found that the probe has a detection limit of 0.336 μM. Such interesting results could be further supported by quantum chemical calculation, UV and 1H NMR titration. Moreover, the probe is applied to determine iodide in powdered milk and urine samples. This experiment shows a good agreement between added and detected concentration of the iodide in real samples.
- Yang, Wen,Shao, Jie,Xu, Yunlong,Zhou, Weiqun,Xie, Juan
-
-
Read Online
- 1,3-Thiazepines. 2. Reaction of 2-iminohexahydrothiazepines with phenylisocyanate and isothiocyanates
-
We have shown that as a result of reaction of phenylisocyanate with 2-benzyl- and 2-aryliminohexahydrothiazepines, the corresponding N-substituted N-tetrahydroazepinyl-N′-phenylureas are formed. In the case of isothiocyanates, on boiling in different solvents we obtained the products of the exchange reaction; and at room temperature, we also obtained substituted thioureas. We suggest a probable scheme for the process. 1997 Plenum Publishing Corporation.
- Ambartsumova,Levkovich,Abdullaev
-
-
Read Online
- Synthesis methods for isothiocyanate derivative
-
The invention discloses synthesis methods for an isothiocyanate derivative. The first synthesis method includes reacting raw materials, including primary amine, trifluoromethyltrimethylsilane, potassium fluoride and sulfur, with an organic solvent at the room temperature to obtain the isothiocyanate derivative. The synthetic isothiocyanate derivative has the advantages of simple operation, safety,high efficiency, non-toxicity, low raw material price, mild condition, high yield, wide application range of substrates, high compatibility of functional groups and the like. The second synthesis method includes reacting raw materials, including the primary amine, silver trifluoromethane and potassium bromide, with the organic solvent at the room temperature to obtain the isothiocyanate derivative. The isothiocyanate derivative has the advantages of simple operation, safety, high efficiency, easy availability of the raw materials, nearly quantitative yield, wide application range of the substrates, applicability to selective post-modification of drugs or complex compounds, and the like.
- -
-
Paragraph 0033; 0034; 0035; 0036; 0041; 0042; 0043; 0044
(2019/05/22)
-
- Synthesis of thiocarbamoyl fluorides and isothiocyanates using CF3SiMe3 and elemental sulfur or AgSCF3 and KBr with amines
-
Reactions of thiocarbonyl fluoride derived from cheap, readily available, and widely used CF3SiMe3, elemental sulfur, and KF with secondary amines and primary amines at room temperature in THF provided a wide variety of thiocarbamoyl fluorides and isothiocyanates in moderate to excellent yields, respectively. The two reactions show broad substrate scope and good functional group tolerance. Moreover, AgSCF3 reacts with secondary/primary amines under KBr at room temperature, affording quantitative thiocarbamoyl fluorides/isothiocyanates, which feature late-stage application.
- Zhen, Long,Fan, Hui,Wang, Xiaoji,Jiang, Liqin
-
supporting information
p. 2106 - 2110
(2019/03/26)
-
- Reaction of Thiocarbonyl Fluoride Generated from Difluorocarbene with Amines
-
The reaction of thiocarbonyl fluoride, generated from difluorocarbene, with various amines under mild conditions is described. Secondary amines, primary amines, and o-phenylenediamines are converted to thiocarbamoyl fluorides, isothiocyanates, and difluoromethylthiolated heterocycles, respectively. Thiocarbamoyl fluorides were further transformed into trifluoromethylated amines by using a one-pot process. Thiocarbonyl fluoride is generated in situ and is rapidly fully converted in one pot under mild conditions; therefore, no special safety precautions are needed.
- Yu, Jiao,Lin, Jin-Hong,Xiao, Ji-Chang
-
supporting information
p. 16669 - 16673
(2017/12/07)
-
- Alkali-free green synthetic isothiocyanate method
-
The invention discloses an alkali-free green synthetic method for isothiocyanate, and relates to the field of organic chemical industry. The method includes the steps: (1) adding solvents into carbon sulfide reagents and primary amine serving as raw materials, performing organic reaction at the temperature of 100-150 DEG C for 10-30 hours; (2) cooling and spin-drying the raw materials after reaction, adding dichloromethane, extracting and separating organic phases by 10% of dilute hydrochloride acid, washing the organic phases, combining the organic phases into an organic layer, washing the organic layer with saturated salt water, drying the organic layer by anhydrous Na2SO4, and performing column chromatographic separation to obtain the isothiocyanate. The molar ratio of the carbon sulfide reagents to the primary amine is 1:1.2-3. Compared with a preparation method in the prior art, the method has the advantages that only heating reaction needs to be performed in the solvents, additional alkali is omitted, and the method is greener and more environmentally friendly and has better application values.
- -
-
Paragraph 0024; 0025; 0026; 0036; 0037; 0038
(2017/08/26)
-
- Aminothiazole compound, and preparation method and application thereof
-
The invention discloses an aminothiazole compound, and a preparation method and an application thereof. The compound has a following structural formula. In the formula, n, m, x are all 0 or 1, and only one of the three is 1 or the three are 0 at a same time; R1 is hydrogen, 2-pyridyl, 3-pyridyl, 4-pyridyl, phenyl, 2-pyrazinyl, 2-furyl, 2-thienyl, 2-pyrrolyl, 2-quinolyl, or 2-methylenepyridine; R2 is hydrogen or alkane with 1-10 aliphatic carbon chains; R3 or R4 is hydrogen or as the picture; R5 is hydrogen, a structure as the picture, N,N-diethyl, N,N-dipropyl, methyl, ethyl, propyl, butyl, trifluoromethyl, methoxy or cyano; among R3, R4 and R5, two are hydrogen at a same time; R6 and R7 can be same or different, and can be H, alkane with 1-10 aliphatic carbon chains, olefin or alkyne. In animal bodies, the compounds can inhibit the proliferation and growth of KRAS high mutant tumors such as pancreatic cancer and colon cancer.
- -
-
Paragraph 0042; 0043; 0044
(2016/10/08)
-
- Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses
-
There are currently no drugs available for the treatment of enterovirus (EV)-induced acute and chronic diseases such as the common cold, meningitis, encephalitis, pneumonia, and myocarditis with or without consecutive dilated cardiomyopathy. Here, we report the discovery and characterization of pyrazolopyrimidines, a well-tolerated and potent class of novel EV inhibitors. The compounds inhibit the replication of a broad spectrum of EV in vitro with IC50 values between 0.04 and 0.64 μM for viruses resistant to pleconaril, a known capsid-binding inhibitor, without affecting cytochrome P450 enzyme activity. Using virological and genetics methods, the viral capsid was identified as the target of the most promising, orally bioavailable compound 3-(4-trifluoromethylphenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine (OBR-5-340). Its prophylactic as well as therapeutic application was proved for coxsackievirus B3-induced chronic myocarditis in mice. The favorable pharmacokinetic, toxicological, and pharmacodynamics profile in mice renders OBR-5-340 a highly promising drug candidate, and the regulatory nonclinical program is ongoing. Curing the common cold! A cluster of pyrazolopyrimidines with potent broad-spectrum activity against enteroviruses was discovered. Extensive structure-property relationship analyses led to the identification of 3-(4-trifluoromethyl-phenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine, shown to be a blocker of the viral capsid protein, as a lead compound for drug development with favorable physicochemical, pharmacokinetic, and toxicological properties.
- Makarov, Vadim A.,Braun, Heike,Richter, Martina,Riabova, Olga B.,Kirchmair, Johannes,Kazakova, Elena S.,Seidel, Nora,Wutzler, Peter,Schmidtke, Michaela
-
supporting information
p. 1629 - 1634
(2015/10/06)
-
- Synthesis of isothiocyanates by reaction of amines with phenyl chlorothionoformate via one-pot or two-step process
-
A facile and efficient synthesis of isothiocyanates from amines is described. This method involves the reaction of amines with phenyl chlorothionoformate in the presence of solid sodium hydroxide by either a one-pot process or a two-step approach. The one-pot process is useful for preparing alkyl and electron-rich aryl isothiocyanates, whereas the two-step approach is more versatile, working very well not only for alkyl and electron-rich aryl isothiocyanates, but also for highly electron-deficient aryl and heterocyclic isothiocyanates. Georg Thieme Verlag Stuttgart, New York.
- Li, Zheng-Yi,Ma, Hong-Zhao,Han, Chen,Xi, Hai-Tao,Meng, Qi,Chen, Xin,Sun, Xiao-Qiang
-
p. 1667 - 1674
(2013/07/19)
-
- Synthesis and SAR of selective small molecule neuropeptide y Y2 receptor antagonists
-
Highly potent and selective small molecule neuropeptide Y Y2 receptor antagonists are reported. The systematic SAR exploration of a hit molecule N-(4-ethoxyphenyl)-4-[hydroxy(diphenyl)methyl]piperidine-1-carbothioamide, identified from HTS, led to the discovery of highly potent NPY Y2 antagonists 16 (CYM 9484) and 54 (CYM 9552) with IC50 values of 19 nM and 12 nM respectively.
- Mittapalli, Gopi Kumar,Vellucci, Danielle,Yang, Jun,Toussaint, Marion,Brothers, Shaun P.,Wahlestedt, Claes,Roberts, Edward
-
scheme or table
p. 3916 - 3920
(2012/07/03)
-
- Triphosgene: An efficient catalyst for synthesis of isothiocyanates
-
Isothiocyanates are bioactive molecules that show various biological activities such as antifungal and anathematic activities. They play a vital role in the synthesis of various heterocyclic compounds. Various isothiocyanates were prepared in good to high yield using triphosgene. Copyright Taylor & Francis Group, LLC.
- Chaskar,Yewale,Bhagat,Langi
-
p. 1972 - 1975
(2008/09/21)
-
- Regioselective covalent modification of hemoglobin in search of antisickling agents
-
Although the molecular defect in sickle hemoglobin that produces sickle cell disease has been known for decades, there is still no effective drug treatment that acts on hemoglobin itself. In this work, a series of diversely substituted isothiocyanates (R-NCS) were examined for their regioselective reaction with hemoglobin in an attempt to alter the solubility properties of sickle hemoglobin. Electrospray mass spectrometry, molecular modeling, X-ray crystallography, and conventional protein chemistry were used to study this regioselectivity and the resulting increase in solubility of the modified hemoglobin. Depending on the attached R-group, the isothiocyanates were found to react either with the Cysβ93 or the N-terminal amine of the α-chain. One of the most effective compounds in the series, 2-(N,N-dimethylamino)ethyl isothiocyanate, selectively reacts with the thiol of Cysβ93 which, in conjunction with the cationic group, was seen to perturb the local hemoglobin structure. This modified HbS shows an approximately 30% increase in solubility for the fully deoxygenated state, along with a significant increase in oxygen affinity. This compound and a related analogue appear to readily traverse the erythrocyte membrane. A discussion of the relation of these structural changes to inhibition of gelation is presented. The dual activities of increasing HbS oxygen affinity and directly inhibiting deoxy HbS polymerization, in conjunction with facile membrane traversal, suggest that these cationic isothiocyanates show substantial promise as lead compounds for development of therapeutic agents for sickle cell disease.
- Park, Soobong,Hayes, Brittany L.,Marankan, Fatima,Mulhearn, Debbie C.,Wanna, Linda,Mesecar, Andrew D.,Santarsiero, Bernard D.,Johnson, Michael E.,Venton, Duane L.
-
p. 936 - 953
(2007/10/03)
-
- Hydrolysis of N-aryl thioncarbamate esters. Modified Marcus equation for reactions with asymmetric intrinsic barriers
-
The hydrolysis of ethyl N-p-substituted arylthioncarbamates was studied at 100°C in the pH range 6.5-12.5. No general catalysis was found, and the presence of an isothiocyanate intermediate was detected, indicating that the alkaline hydrolysis occurs by an E1cb mechanism. From the pH-rate profiles, the first-order rate constants kE for the elimination step of the thioncarbamate anion forming the isothiocyanate intermediate were determined. The alkaline hydrolysis of p-substituted arylisothiocyanates was studied at 25°C in 0.1-0.3 M solutions of NaOH and in 0.1-0.3 M aqueous ethanol solutions, at different concentrations of NaOH. The second-order rate constants for the addition reaction with hydroxide (kOH) and ethoxide (kA) ions were obtained. Leffler plots for the elimination of the ethoxide ion from the arylthioncarbamate anion and for the addition of the ethoxide ion to the arylisothiocyanate were linear. From Leffler's equation, with the sole condition that dαL/dΔG should be constant, a modified Marcus equation (MME) was obtained, where a parameter p (or q for the reverse reaction) defined the asymmetry of the intrinsic barrier. (When p = 1/2 the barrier is symmetric and the MME becomes the Marcus equation in the usual form.) For the addition-elimination reaction studied, both Leffler plots were adjusted to MME with the asymmetric parameter p = 0.694 ± 0.002 for the addition and q = 0.307 ± 0.002 for the elimination reaction. The intrinsic barrier was ΔG0≠ = 24.75 ± 0.02 kcal mol-1 and |ΔGmax| = 438 ± 4 kcal mol-1 (1 kcal = 4.184 kJ). The addition reaction was exoergic and, as expected from the high intrinsic barrier, αL changed very little in the series (0.679-0.683); the transition state was product-like, and it moved towards the reagents with increasing exoergicity. Copyright
- Humeres, Eduardo,Zucco, Cesar,Nunes, Mauricea,Debacher, Nito A.,Nunes, Ricardo J.
-
p. 570 - 575
(2007/10/03)
-
- Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their biological evaluation as urokinase inhibitors
-
The serine protease urokinase (uPa) has been implicated in the progression of both breast and prostate cancer. Utilizing structure based design, the synthesis of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-carboxamidines is described. Further optimization of this series by substitution of the terminal amine yielded urokinase inhibitors with excellent activities.
- Wilson, Kenneth J.,Illig, Carl R.,Subasinghe, Nalin,Hoffman, James B.,Jonathan Rudolph,Soll, Richard,Molloy, Christopher J.,Bone, Roger,Green, David,Randall, Troy,Zhang, Marie,Lewandowski, Frank A.,Zhou, Zhao,Sharp, Celia,Maguire, Diane,Grasberger, Bruce,DesJarlais, Renee L.,Spurlino, John
-
p. 915 - 918
(2007/10/03)
-
- Experimental and Theoretical Studies of Substituent Effects in Hydrogen Bond Based Molecular Recognition of a Zwitterion by Substituted Arylureas
-
Electron withdrawing groups have a strong effect on hydrogen bonding to aryl ureas.The effect of para substituents modestly exceeds the effect of meta substituents.Among common substituent parameters, ?- (ρ = 1.77, r2 = 0.988) is found to be the best predictor for the observed effects of para substituents in aryl ureas.Semi-empirical and ab initio methods are used to calculate charge distributions in substituted benzene derivatives and in these ureas.A comparison of experimental and predicted (AM1, STO3G, 321-G*, 631-G**) dipole moments of benzene derivatives is presented.It is shown that calculated surface electric potentials for these thioureas succesfully predict the relative hydrogen bonded association energies.
- Wilcox, Craig S.,Kim, Eun-il,Romano, David,Kuo, Lung Huang,Burt, Arthur L.,Curran, Dennis P.
-
p. 621 - 634
(2007/10/02)
-
- Synthesis of 4-Substituted Thiosemicarbazones of 3-Methyl-4-phenylpyridine-2-carboxaldehyde as Antitumor Agents
-
A convenient synthesis of 3-methyl-4-phenylpyridine-2-carboxaldehyde (4) is described.Reaction of 4 with 4-substituted thiosemicarbazides (6) gives thiosemicarbazones (7) some of which (7b, 7g, 7i and 7j) exhibit significant antitumor activity in animals.Thiosemicarbazides (6e - 6j) have been prepared from the corresponding isothiocyanates (5) (which result from sodium chlorite oxidation of the addition products of CS2 and the appropriate amine) and hydrazine.Isomerisation of 1,3-dimethyl-4-phenyl-1,2,3,6-tetrahydropyridine (Δ4-isomer) to 1,2,5,6-tetrahydro analog (Δ3-isomer, 1) has been effected with refluxing conc.HCl.
- Rahman, M. F.
-
p. 828 - 830
(2007/10/02)
-