- Anionic fluorescent probe, preparation method and application thereof
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The invention discloses an anionic fluorescent probe, and a preparation method and an application thereof. The anionic fluorescent probe is prepared by mixing 1-(4-amino) phenyl-1, 2, 2-triphenylethylene with a phenyl isothiocyanate derivative and carrying out a condensation reaction. The fluorescent probe has selectivity on anions and can be used for quantitatively analyzing the recognized anions.
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Paragraph 0032; 0043-0044
(2021/05/01)
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- USP8 inhibitor, preparation method and applications thereof
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The invention discloses a USP8 inhibitor, a preparation method and applications thereof, belongs to the field of medicinal chemistry, and particularly relates to a class of USP8 inhibitors (I) containing substituted thiourea or substituted guanidine derivatives, and a preparation method thereof. According to the invention, the results of biological experiments prove that the compound has good USP8inhibitory activity and cell activity and can be used for treating diseases such as malignant tumors and the like.
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Paragraph 0107-0110
(2020/06/02)
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- Discovery of novel USP8 inhibitors via Ubiquitin-Rho-110 fluorometric assay based high throughput screening
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USP8, one member of deubiquitinating enzymes (DUBs) families, maintains the ubiquitination level of EGFR and regulates the downstream signaling pathways. The deregulation of USP8 has been implicated in many human diseases, especially in cancer. Therefore, USP8 has been identified as a promising target for drug design. Herein, via high throughput screening based on Ubiquitin-rhodamine-110 (Ubiquitin-Rho-110) fluorometric activity assay, we discovered a novel inhibitor DC-U43. By structure optimization, DC-U43-10 reached a half-maximal inhibitory concentration (IC50) value of 2.6 ± 1.1 μM and exhibited 10-fold selectivity against USP7. The binding between DC-U43-10 and USP8 was validated by surface plasmon resonance (SPR) assay with a KD value of 10.5 ± 3.7 μM. It also inhibited the colony formation of H1975 cells. Hence, DC-U43-10 represents a kind of USP8 inhibitors with novel scaffold and has broad prospects for being a probe for USP8-related academic and clinical research.
- Bian, Jinlei,Chen, Kaixian,Ding, Hong,Han, Jie,Jiang, Hualiang,Li, Zhiyu,Luo, Cheng,Ma, Zengyi,Tian, Yucheng,Wang, Jubo,Xu, Xi,Yu, Liang,Zhang, Qilin,Zhang, Yichao,Zhao, Yao
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- Highly Acidic Conjugate-Base-Stabilized Carboxylic Acids Catalyze Enantioselective oxa-Pictet–Spengler Reactions with Ketals
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Acyclic ketone-derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone-derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well-known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion-binding to a thiourea site.
- Zhu, Zhengbo,Odagi, Minami,Zhao, Chenfei,Abboud, Khalil A.,Kirm, Helmi Ulrika,Saame, Jaan,L?kov, M?rt,Leito, Ivo,Seidel, Daniel
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supporting information
p. 2028 - 2032
(2019/12/24)
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- Synthesis of thiocarbamoyl fluorides and isothiocyanates using amines with CF3SO2Cl
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A practical and efficient method to synthesize thiocarbamyl fluorides and isothiocyanates from amines with trifluoromethanesulfonyl chloride was developed. In the presence of the reducing agent triphenylphosphine and sodium iodide, thiocarbamyl fluorides and isothiocyanates were synthesized from secondary/primary amine in moderate to excellent yields, respectively. A broad scope of substrates and good functional group compatibility were observed.
- Jiang, Lvqi,Yi, Wenbin,Wei, Jingjing,Liang, Shuaishuai
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p. 12374 - 12381
(2020/11/10)
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- Triton-B catalyzed one pot multicomponent synthesis of isothiocyanates in non-aqueous medium
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A facile and novel method to synthesize isothiocyanides from cyclic and acyclic amines and carbon disulphide in DMSO with Triton-B as catalyst in non-aqueous medium is being reported. The method is less tedious and offers excellent yields. The structures have been elucidated by 1H NMR, 13C NMR and mass spectroscopy.
- Singh, Neha,Khare, Richa
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p. 1636 - 1638
(2019/06/11)
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- Design, synthesis, antiproliferative and antibacterial evaluation of quinazolinone derivatives
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A series of novel quinazolinone derivatives bearing a disulfide bond were designed and synthesized. Their in vitro antiproliferative activities were evaluated using CCK-8 assay against SMMC-7721, Hela, A549 and MCF-7 human cancer cell lines and normal cell lines L929. The preliminary bioassay results demonstrated that all compounds 7a–7h, 8a–8h and 9a–9h exhibited antiproliferation with various degrees, and some compounds showed better effects than positive control 5-fluorouracil against different cancer cell lines. Among these compounds, 8c and 9f showed significant antiproliferative activity against SMMC-7721 cells with IC50 values of 2.88 and 2.56 μM, respectively. In Hela cells, compounds 9c and 9d showed highly effective biological activity with IC50 values of 3.16 and 2.68 μM, respectively. Compounds 7a and 9a exhibited good inhibitory effect against A549 cells with IC50 values of 3.53 and 3.54 μM, respectively. In MCF-7 cells, compounds 7e, 8e and 9e displayed excellent activity with IC50 values of 1.26, 1.12 and 1.85 μM, respectively. Besides, most of the tested compounds showed low cytotoxic effect against the normal cell lines L929. Biological evaluation indicated that all the tested compounds possessed antibacterial activity with certain degrees.
- Wang, Hai-Xin,Liu, Hai-Ying,Li, Wei,Zhang, Shuai,Wu, Zheng,Li, Xin,Li, Cai-Wen,Liu, Yu-Ming,Chen, Bao-Quan
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p. 203 - 214
(2019/01/04)
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- Organophosphine-free copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur
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A copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur in the absence of organophosphine has been established. This approach represents a simple and efficient one-pot synthesis of isothiocyanates, and features excellent functional group tolerance and the use of a cheap, safe and odorless sulfur source. Moreover, this process could directly provide isothiocyanate analogous bioactive molecules, thiocarbonyl-containing pesticides and facile construction of benzoxazole and benzimidazole frames.
- Feng, Wei,Zhang, Xing-Guo
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supporting information
p. 1144 - 1147
(2019/01/28)
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- Isothiocyanate synthesized by three components and preparation method of isothiocyanate
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The invention discloses isothiocyanate and a preparation method thereof. The method comprises the steps that primary amine, sodium difluorobromoacetate and elemental sulfur are taken as reactants forreaction; the reaction is carried out under the action of a copper catalyst, wherein the copper catalyst is any one of cuprous chloride, copper bromide, cuprous iodide, copper chloride and copper trifluoromethanesulfonate; an alkali is also added, wherein the alkali is any one of sodium bicarbonate, potassium carbonate, cesium carbonate, potassium phosphate, DABCO and sodium tert-butoxide; the whole reaction is carried out in a solvent, wherein the solvent is acetonitrile or dimethyl sulfoxide, the reaction temperature is 80-120 DEG C, and the reaction time is 10-14 hours. The method can directly synthesize the target product, does not need to separate intermediate products and only needs stirring and heating reaction under normal pressure to obtain the target product, and the yield can beup to 87%; a waste solution is fewer during the reaction, and the method protects the environment and ensures the health of an operator; in addition, a series of isothiocyanate derivatives can be prepared, and the method has a stronger substrate universality.
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-
Paragraph 0050
(2019/04/26)
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- Differentiating Antiproliferative and Chemopreventive Modes of Activity for Electron-Deficient Aryl Isothiocyanates against Human MCF-7 Cells
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The consumption of Brassica vegetables provides beneficial effects through organic isothiocyanates (ITCs), products of the enzymatic hydrolysis of glucosinolate secondary metabolites. The ITC l-sulforaphane (l-SFN) is the principle agent in broccoli that demonstrates several modes of anticancer action. While the anticancer properties of ITCs like l-SFN have been extensively studied and l-SFN has been the subject of multiple human clinical trials, the scope of this work has largely been limited to those derivatives found in nature. Previous studies have demonstrated that structural changes in an ITC can lead to marked differences in a compound's potency to 1) inhibit the growth of cancer cells, and 2) alter cellular transcriptional profiles. This study describes the preparation of a library of non-natural aryl ITCs and the development of a bifurcated screening approach to evaluate the dose- and time-dependence on antiproliferative and chemopreventive properties against human MCF-7 breast cancer cells. Antiproliferative effects were evaluated using a commercial MTS cell viability assay. Chemopreventive properties were evaluated using an antioxidant response element (ARE)-promoted luciferase reporter assay. The results of this study have led to the identification of 1) several key structure–activity relationships and 2) lead ITCs for continued development.
- Anderson, Ruthellen H.,Lensing, Cody J.,Forred, Benjamin J.,Amolins, Michael W.,Aegerter, Cassandra L.,Vitiello, Peter F.,Mays, Jared R.
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p. 1695 - 1710
(2018/08/01)
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- p-Aromatic Isothiocyanates: Synthesis and Anti Plant Pathogen Activity
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In this study, a series of p-aromatic isothiocyanates are prepared by reacting p-aromatic amines with carbon disulphide and further treating with molecular iodine to yield corresponding isothiocyanate derivatives. The structures of newly synthesized compounds are confirmed by IR, NMR, and MS data. Activity of the products against plant pathogenic fungi and bacteria is tested and the structure-activity relationship is approached. p-Nitrophenyl isothiocyanate most efficiently inhibits Rhizoctonia solani and Erwinia carotovora. The order of seven aromatic isothiocyanates antifungicidal activity is following: p-nitrophenyl > p-methoxyphenyl > p-chlorophenyl > p-methylphenyl > p-ethylphenyl > phenyl > p-fluorophenyl. For antibacterial activity, the order was p-nitrophenyl > p-chlorophenyl > p-methylphenyl > p-ethylphenyl > p-fluorophenyl > phenyl > p-methoxyphenyl. The present study indicates that some of the compounds exhibit promising antimicrobial activity and can be used as an alternative to the traditional synthetic fungicides for controlling R. solani and E. carotovora.
- Tang,Niu,Wang,Huo,Li,Luo,Cao
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p. 1252 - 1257
(2018/08/16)
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- Dynamic Ureas with Fast and pH-Independent Hydrolytic Kinetics
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Low cost, high performance hydrolysable polymers are of great importance in biomedical applications and materials industries. While many applications require materials to have a degradation profile insensitive to external pH to achieve consistent release profiles under varying conditions, hydrolysable chemistry techniques developed so far have pH-dependent hydrolytic kinetics. This work reports the design and synthesis of a new type of hydrolysable polymer that has identical hydrolysis kinetics from pH 3 to 11. The unprecedented pH independent hydrolytic kinetics of the aryl ureas were shown to be related to the dynamic bond dissociation controlled hydrolysis mechanism; the resulting hindered poly(aryl urea) can be degraded with a hydrolysis half-life of 10 min in solution. More importantly, these fast degradable hindered aromatic polyureas can be easily prepared by addition polymerization from commercially available monomers and are resistant to hydrolysis in solid form for months under ambient storage conditions. The combined features of good stability in solid state and fast hydrolysis at various pH values is unprecedented in polyurea material, and will have implications for materials design and applications, such as sacrificial coatings and biomaterials.
- Cai, Kaimin,Ying, Hanze,Cheng, Jianjun
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supporting information
p. 7345 - 7348
(2018/06/11)
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- Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea against Meloidogyne incognita
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Two series of novel 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea were designed and synthesized. The bioassay results showed that most of the test compounds showed good nematicidal activity against M. incognita at the concentration of 10.0?mg?L?1 in vivo. The compounds A13, A17 and B3 showed excellent nematicidal activity on the second stage juveniles of the root-knot nematode with the inhibition rate of 51.3%, 58.3% and 51.3% at the concentration of 1.0?mg?L?1 respectively. It suggested that the structure of 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea could be optimized further.
- Chang, Yaning,Zhang, Jingwei,Chen, Xiulei,Li, Zhong,Xu, Xiaoyong
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supporting information
p. 2641 - 2644
(2017/05/10)
-
- Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase
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A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (hDHODH) inhibitors. Compounds 26 and 31 displayed IC50 values of 1.75 and 1.12 μM, respectively. The structure-activity relationship was summarized. Further binding mode analysis revealed that compound 31 could form a hydrogen bond with Tyr38 and a water-mediated hydrogen bond with Ala55, which may be necessary for maintaining the bioactivities of the compounds in this series. Further structural optimization of the para- or meta-position of the phenyl group at R will lead to the identification of more potent hDHODH inhibitors.
- Zeng, Fanxun,Qi, Tiantian,Li, Chunyan,Li, Tingfang,Li, Honglin,Li, Shiliang,Zhu, Lili,Xu, Xiaoyong
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supporting information
p. 1297 - 1302
(2017/07/07)
-
- Synthesis and antimicrobial activity of some new 1,2,4-trizoles
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A series of 1,2,4-triazole derivatives were synthesized using appropriate synthetic route and structures were confirmed by IR,1H NMR and elemental analysis. All the synthesized compounds (6a-6h and 7a-7h) were evaluated for antimicrobial activity by determining their minimum inhibitory concentrations (MICs) against a panel of Gram-positive, Gram-negative bacteria and fungi. Most of the compounds showed significant antimicrobial activity against Gram-positive bacteria viz. S. aureus, B. subtilis, Gram-negative bacteria viz. E. coli, P. aerugenosa and fungi viz. C. albicans, A. niger. Some of the compounds showed better antibacterial activities against Gram-positive bacteria compared to Gram-negative bacteria. Compounds 7g, 6g, 6a exhibited good MICs against Gram-positive bacteria and 7f showed better MICs against Gram-negative bacteria compared to reference norfloxacin. Compounds 7f and 7d exhibited MICs which is equipotent to the reference drug ketoconazole.
- Jain, Rakesh Kumar,Mishra, Vikash Kumar,Kashaw, Varsha
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p. 1317 - 1322
(2017/05/02)
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- Alkali-free green synthetic isothiocyanate method
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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.
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-
Paragraph 0024; 0025; 0026; 0039; 0040; 0041
(2017/08/26)
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- Isothiocyanation of amines using the Langlois reagent
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The Langlois reagent was found to be effective for the isothiocyanation of primary amines in the presence of copper iodide and diethyl phosphonate.
- Liao, Yan-Yan,Deng, Jian-Chao,Ke, Yan-Ping,Zhong, Xiao-Lin,Xu, Li,Tang, Ri-Yuan,Zheng, Wenxu
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supporting information
p. 6073 - 6076
(2017/07/10)
-
- Synthesis of Isothiocyanates and Unsymmetrical Thioureas with the Bench-Stable Solid Reagent (Me4N)SCF3
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A highly efficient, selective, and rapid transformation of primary amines and diamines to isothiocyanates and cyclic thioureas is disclosed. As opposed to established approaches that employ toxic or volatile electrophilic liquids and require reaction control (i.e., slow addition, cooling), this protocol utilizes the bench-stable, solid reagent (Me4N)SCF3 at room temperature. The method is characterized by operational simplicity, high speed, efficiency, high functional group tolerance, and late-stage applicability. The byproducts are solids, allowing isolation of the target compounds by filtration.
- Scattolin, Thomas,Klein, Alexander,Schoenebeck, Franziska
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supporting information
p. 1831 - 1833
(2017/04/11)
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- NOVEL BENZIMIDAZOLE BASED EGFR INHIBITORS
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The present invention disclosed a novel EGFR inhibitor compound of formula (I), process for preparation thereof and methods of treating abnormal cell growth in mammals by administering the compounds of formula (I). Wherein, R= -H, 3-CH3, 4-NO2, 4-Cl, 2-CH3, 4-CH3, 4-Br, 4-F R1= -H, -4-OCH3, -4-NO2,-2-NO2, -4-Cl, -2,4,6-CH3, -4-CH3, -2-F,4-Br, -4-CF3, -4-S-CH3, -4-Cl,-3-CF3, -3-S-CH3, -3,5-CF3, -2-S-CH3, -3-CF3,-4-OCF3, -Si-(CH3)3, -Si-(C2H5)3, (CH3)2-Si- C2H5.
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Page/Page column 12
(2016/06/15)
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- Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses
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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
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supporting information
p. 1629 - 1634
(2015/10/06)
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- Purification-free, small-scale synthesis of isothiocyanates by reagentless fragmentation of polymer-supported 1,4,2-oxathiazoles
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The synthesis of isothiocyanates (ITCs) by employing polymer-supported 1,4,2-oxathiazoles is described. The ITCs are obtained in moderate yields and high purity through a reagentless, thermal fragmentation of polymer-supported 1,4,2-oxathiazoles that are obtained by trapping nitrile oxides with polymer-supported thiocarbonates. A purification-free, small-scale synthesis for isothiocyanates (ITCs) is reported that proceeds through a catch-and-release system. This is a convenient method to produce small quantities of ITCs in high purity for screening purposes. Copyright
- Burkett, Brendan A.,Fu, Pincheng,Hewitt, Russell J.,Ng, Su Ling,Toh, Joel D. W.
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p. 1053 - 1058
(2014/03/21)
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- Purification-Free, Small-Scale Synthesis of Isothiocyanates by Reagentless Fragmentation of Polymer-Supported 1,4,2-Oxathiazoles
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The synthesis of isothiocyanates (ITCs) by employing polymer-supported 1,4,2-oxathiazoles is described. The ITCs are obtained in moderate yields and high purity through a reagentless, thermal fragmentation of polymer-supported 1,4,2-oxathiazoles that are obtained by trapping nitrile oxides with polymer-supported thiocarbonates. A purification-free, small-scale synthesis for isothiocyanates (ITCs) is reported that proceeds through a catch-and-release system. This is a convenient method to produce small quantities of ITCs in high purity for screening purposes.
- Burkett, Brendan A.,Fu, Pincheng,Hewitt, Russell J.,Ng, Su Ling,Toh, Joel D. W.
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p. 1053 - 1058
(2015/10/05)
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- Facile and versatile synthesis of alkyl and aryl isothiocyanates by using triphosgene and cosolvent
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A mild and efficient method for the conversion of alkyl and aryl amines to isothiocyanates via dithiocarbamates has been developed using (CH 3)2CO-CS2 as co-solvent and triphosgene as dehydrosulfurization reagent. High yields, mild reaction conditions and excellent functional group compatibility make it become a versatile synthetic method for the preparation of isothiocyanates compared with reported methods. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Liu, Pengfei,Li, Chunyan,Zhang, Jingwei,Xu, Xiaoyong
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supporting information
p. 3342 - 3351
(2013/10/01)
-
- Synthesis of isothiocyanates by reaction of amines with phenyl chlorothionoformate via one-pot or two-step process
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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
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p. 1667 - 1674
(2013/07/19)
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- A simple and straightforward synthesis of phenyl isothiocyanates, symmetrical and unsymmetrical thioureas under ball milling
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Promoted by KOH under ball milling, anilines were efficiently transformed into isothiocyanates (in presence of 5.0 equiv. CS2) or symmetrical thioureas (in presence of 1.0 equiv. CS2), without using any other harsh or toxic decomposition reagent. Some in situ generated isothiocyanates can directly "click" with other amines to afford unsymmetrical thioureas.
- Zhang, Ze,Wu, Hao-Hao,Tan, Ya-Jun
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p. 16940 - 16944
(2013/09/24)
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- The rapid generation of isothiocyanates in flow
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Isothiocyanates are versatile starting materials for a wide range of chemical reactions. However, their high nucleophilic susceptibility means they are best prepared and used immediately. We report here on a flow platform for the fast and efficient formation of isothiocyanates by the direct conversion of easily prepared chloroximes. To expedite this chemistry a flow insert cartridge containing two immobilised reagents is used to affect the chemical transformation which typically eliminates the requirements for any conventional work-up or purification of the reaction stream.
- Baumann, Marcus,Baxendale, Ian R.
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supporting information
p. 1613 - 1619
(2013/10/22)
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- Synthesis of new enantiopure thioureas derived from (S)-proline
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Enantiopure thiourea derivatives, containing pyrrolidine ring, were prepared by the reaction of N-Boc-(S)-2-aminomethylpyrrolidine (6) with thioisocyanates 8.
- Wroblewska, Aneta,Mloston, Grzegorz
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p. 509 - 511
(2013/07/25)
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- A general and facile one-pot process of isothiocyanates from amines under aqueous conditions
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A general and facile one-pot protocol for the preparation of a broad range of alkyl and aryl isothiocyanates has been developed from their corresponding primary amines under aqueous conditions. This synthetic process involves an in situ generation of a dithiocarbamate salt from the amine substrate by reacting with CS2 followed by elimination to form the isothiocyanate product with cyanuric acid as the desulfurylation reagent. The choice of solvent is of decisive importance for the successful formation of the dithiocarbamate salt particularly for highly electron-deficient substrates. This novel and economical method is suitable for scale-up activities.
- Sun, Nan,Li, Bin,Shao, Jianping,Mo, Weimin,Hu, Baoxiang,Shen, Zhenlu,Hu, Xinquan
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experimental part
p. 61 - 70
(2012/04/04)
-
- Synthesis and pharmacological evaluation of 2,4-dinitroaryldithiocarbamate derivatives as novel monoacylglycerol lipase inhibitors
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Monoacylglycerol lipase (MAGL) is responsible for signal termination of 2-arachidonoylglycerol (2-AG), an endocannabinoid neurotransmitter endowed with several physiological effects. Previously, we showed that the arylthioamide scaffold represents a privileged template for designing MAGL inhibitors. A series of 37 compounds resulting from pharmacomodulations around the arylthioamide template were synthesized and tested to evaluate their inhibitory potential on MAGL activity as well as their selectivity over fatty acid amide hydrolase (FAAH), another endocannabinoid-hydrolyzing enzyme. We have identified 2,4-dinitroaryldithiocarbamate derivatives as a novel class of MAGL inhibitors. Among the synthesized compounds, we identified [2,4-dinitrophenyl-4-(4-tert- butylbenzyl)piperazine-1-carbodithioate] (CK37), as the most potent MAGL inhibitor within this series (IC50 = 154 nM). We have also identified [2,4-dinitrophenyl-4-benzhydrylpiperazine-1-carbodithioate] (CK16) as a selective MAGL inhibitor. These compounds are irreversible MAGL inhibitors that probably act by interacting with Cys208 or Cys242 and Ser122 residues of the enzyme. Moreover, CK37 is able to raise 2-arachidonoylglycerol (2-AG) levels in intact cells.
- Kapanda, Coco N.,Masquelier, Julien,Labar, Geoffray,Muccioli, Giulio G.,Poupaert, Jacques H.,Lambert, Didier M.
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supporting information; experimental part
p. 5774 - 5783
(2012/07/28)
-
- Benzothiazoles: Search for anticancer agents
-
Novel derivatives of 2-amino benzothiazoles 4(a-j) have been synthesized and tested for their antitumor activity using National Cancer Institute (NCI) disease oriented antitumor screen protocol against nine panel of cancer cell lines. Among the synthesized compounds, two compounds were granted NSC code and screened at National Cancer Institute (NCI)-USA for anticancer activity at a single high dose (10-5 M) and five dose in full NCI 60 cell panel. Among the selected compounds, 7-chloro-N-(2,6-dichlorophenyl)benzo[d]thiazol-2- amine (4i) with GI50 values of 7.18 × 10-8 M against Non-Small Cell HOP-92 Lung Cancer cell line proved to be the most active members in this study. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors.
- Noolvi, Malleshappa N.,Patel, Harun M.,Kaur, Manpreet
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scheme or table
p. 447 - 462
(2012/10/08)
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- Novel platinum(II) and palladium(II) complexes of thiosemicarbazones derived from 5-substitutedthiophene-2-carboxaldehydes and their antiviral and cytotoxic activities
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A series of thiosemicarbazones and their platinum(II) and palladium(II) complexes have been synthesized. The chemical structures of ligands and their complexes were characterized by UV-Vis, IR, 1H NMR, 13C NMR, MS spectra, elemental analysis and TGA. The antiviral and cytotoxic activities of all compounds have been tested. Results of broad antiviral evaluation showed that none of the compounds evaluated endowed with anti-DNA or -RNA virus activity at subtoxic concentrations except for the palladium complex 1b. This compound exhibited slightly selective inhibition against cytomegalovirus. The platinum complex 4a exhibited the best cytostatic activities against human cervix carcinoma. Ligands 2, 4 and 5 showed cytostatic potential. The palladium complexes were in general less cytostatic than the corresponding platinum complexes or unliganded congeners.
- Karakü?ük-Iyido?an, Ay?egül,Ta?demir, Demet,Oru?-Emre, Emine El?in,Balzarini, Jan
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scheme or table
p. 5616 - 5624
(2012/01/03)
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- Synthesis of 2-iminothiophen-3(2H)-ones from 3H-1,2-dithiol-3-ones
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3H-1,2-Dithiol-3-ones undergo a new transformation into 2-iminothiophen-3(2H)-ones upon treatment with isonitriles; the structure of iminothiophenone 10 was confirmed by X-ray diffraction analysis.
- Ogurtsov, Vladimir A.,Karpychev, Yurii V.,Pestravkina, Dar'Ya A.,Belyakov, Pavel A.,Nelyubina, Yulia V.,Rakitin, Oleg A.
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experimental part
p. 282 - 284
(2011/05/15)
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- Menthone semicarbazides and thiosemicarbazides as anticonvulsant agents
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A series of novel (±) 3-menthone semicarbazides (1-7) and thiosemicarbazides (8-14) were synthesized using an appropriate synthetic route and characterized by thin layer chromatography and spectral analysis. The anticonvulsant activity of synthesized compounds was established after intraperitoneal administration in three seizure models in mice which include maximal electroshock seizure (MES), subcutaneous pentylene tetrazole (scPTZ) induced seizure and minimal neurotoxicity test. Seven compounds exhibited protection in both models and N1 - (4-fluorophenyl) - N4- (menth-3-one) semicarbazide (4) emerged as the most active compound with MES ED50 of 44.15mg/kg and scPTZ ED50 of 38.68mg/kg at 0.25h duration. These compounds were found to elevate γ-amino butyric acid (GABA) levels in the midbrain region, thus indicating that (±) 3-menthone semicarbazides could be considered as a lead molecule in designing of a potent anticonvulsant drug.
- Jain, Endra,Kumar,Stables, James,Sinha, Reema
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experimental part
p. 44 - 50
(2011/11/12)
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- Modified julia-kocienski reaction promoted by means of m-NPT (nitro-phenyltetrazole) sulfone
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m-Nitrophenyltetrazole sulfone (2) was employed in the Julia-Kocienski reaction. The olefination reaction between 2 and carbonyl compounds proceeded smoothly under Masamune-Roush conditions (DBU and LiCl). These conditions were also applicable to our catechin derivative synthesis. Furthermore, phenolic mesylate was also tolerated in this mild reaction.
- Sakai, Yuki,Ikeuchi, Kazutada,Yamada, Yuji,Wakimoto, Toshiyuki,Kan, Toshiyuki
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scheme or table
p. 827 - 829
(2010/06/12)
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- Novel synthesis of anthelmintic drug 4-isothiocyanato-4′- nitrodiphenyl ether and its analogs
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An efficient, mild, chemoselective, and convenient protocol for synthesis of isothiocyanate derivatives. This protocol was applied successfully in the novel synthesis of anthelmintic drug 4-isothiocyanato-4′-nitrodiphenyl ether and its analogs. Copyright Taylor & Francis Group, LLC.
- Chaskar,Bandgar,Modhave,Patil,Yewale
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body text
p. 992 - 1001
(2009/09/08)
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- Diethyl chlorophosphate: A mild and versatile reagent for the one-pot preparation of isothiocyanates from amines
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A simple, efficient, and new method has been developed for the synthesis of isothiocyanates from amines. The reaction of a variety of aromatic and aliphatic amines with carbon disulfide in the presence of diethyl chlorophosphate as an efficient reagent proceeded effectively to afford the corresponding isothiocyanates in moderate yields. This method is easy, rapid, and moderate-yielding for the synthesis of isothiocyanates from amines. Georg Thieme Verlag Stuttgart.
- Kaboudin, Babak,Jafari, Ehsan
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experimental part
p. 2683 - 2685
(2009/04/04)
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- Kinetic and mechanistic study on the thermal reactivity of stabilized phosphorus ylides, part 3: [(Acetyl) (arylcarbamoyl)-methylene] triphenylphosphoranes and [(alkoxy-carbonyl) (arylcarbamoyl)-methylene] triphenylphosphoranes and their thiocarbamoyl analogues
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A series of five [(acety])(arylcarbabmoyl)methylene]triphenyl-phosphoranes 1a-e and their thiocarbamoyl analogues 2a-e, |(alkoxycarbonyl)(arylcarbamoyl) methylene]triphenylphosphoranes 3a-e and thiocarbamoyl analogues 4a-e were prepared and fully characterized. All ylides are found under conditions of flash vacuum pyrolysis to fragment giving arylisocyanate or isothiocyanate and acetyl ylides or alkoxy ylides which undergo thermal extrusion of Ph3PO. A kinetic study shows that these reactions are unimolecular and are of first-order nature with no significant substituent effect. The thiocarbamoyl ylides 2 react from 4.6 to 42 times faster than their carbamoyl ylides 1, while the thiocarbamoyl ylides 4 react from 6.6 to 20.9 times faster than their carbamoyl ylides 3.
- Aitken, R. Alan,Al-Awadi, Nouria A.,Dawson, Graham,El-Dusouqui, Osman,Kaul, Kamini,Kumar, Ajith
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- Synthesis of mesoionic 4-(para-substituted phenyl-5-2,4-dichlorophenyl)-1, 3-4-thiadiazolium-2-aminides by direct cyclization via acylation of thiosemicarbazides
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The synthesis of ten novel mesoionic 4-[para-substituted (H, CH 3, OCH3, NO2, Cl, Br, OH, t-C4H 9, C6H5, C4H9) phenyl-5-2,4-dichlorophenyl]-1,3-4-thiadiazolium-2-aminides, as hydrochlorides, are described. The synthesis strategy utilized the corresponding para-substituted isothiocyanates as starting materials to obtain the thiosemicarbazides through reaction with phenylhydrazine (61-98%), which were then submitted to acylation with 2,4-dichloro benzoyl chloride and direct cyclization to generate the desired substituted mesoionic compounds in good yields (ca. 80%). Copyright Taylor & Francis Group, LLC.
- Britto, Marcelo Moreira,Almeida, Tania Mara Grigolli,Leitao, Andrei,Donnici, Claudio Luis,Lopes, Miriam Tereza Paz,Montanari, Carlos Alberto
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p. 3359 - 3369
(2007/10/03)
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- Synthesis, thermal reactivity and kinetics of substituted [(benzoyl)(phenylcarbamoyl)methylene]triphenylphosphoranes and their thiocarbamoyl analogues
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A range of 16 substituted benzoyl/arylcarbamoyl and benzoyl/ arylthiocarbamoyl stabilised ylides have been prepared. They are found under conditions of flash vacuum pyrolysis to fragment giving a benzoyl ylide and aryl isocyanate or isothiocyanate accompanied in some cases by secondary pyrolysis products. Kinetic studies show the thiocarbamoyl ylides to react consistently faster than their carbamoyl analogues and substituent effects suggest a polar cyclic transition state, which involves attack by the benzoyl oxygen on the carbamoyl/thiocarbamoyl NH. Graphical Abstract.
- Aitken, R. Alan,Al-Awadi, Nouria A.,Dawson, Graham,El-Dusouqi, Osman M.E.,Farrell, Dorcas M.M.,Kaul, Kamini,Kumar, Ajith
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p. 129 - 135
(2007/10/03)
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- Reactions of arenediazonium tetrafluoroborates with 1,4-bis(acryloyloxy)butane in the presence of thiocyanate ion
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The first thiocyanatoarylation reaction with an unsaturated compound containing two isolated multiple bonds, 1,4-bis(acryloyloxy)butane, was effected. The reactions of 1,4-bis(acryloyloxy)butane with arenediazonium tetrafluoroborates occur in aqueous acet
- Gorbovoi,Baranovskii,Koval'skii,Grishchuk
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p. 1230 - 1232
(2007/10/03)
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- Hydrolysis of N-aryl thioncarbamate esters. Modified Marcus equation for reactions with asymmetric intrinsic barriers
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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.
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p. 570 - 575
(2007/10/03)
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- A new synthesis of aryl isothiocyanates: Carbon disulfide as a dipolarophile. The reaction of (4,5,6,7-tetrahydro-2H-1,2,3-benzotriazolium-1-yl)arylaminide 1,3-dipoles with carbon disulfide: Synthesis, kinetics, mechanism. Azolium 1,3-dipoles
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A new synthesis of aryl isothiocyanates in which the aryl nitrogen moiety ultimately comes from an arylhydrazine is described. Treatment of (4,5,6,7-tetrahydro-2H-1,2,3-benzotriazolium-1-yl)arylaminide 1,3-dipoles (derived from cyclohexane-1,2-dione bis(arylhydrazones)) with carbon disulfide in acetone at ambient temperatures gives high yields of aryl isothiocyanates and 2-aryl-4,5,6,7-tetrahydro-2H-1,2,3-benzotriazole as a leaving group. The kinetics and mechanism of the reaction were investigated. The mechanism involves a polar cycloaddition of the triazolium-aminide to the CS2 generating a partially ring-closed intermediate which fragments to the aryl isothiocyanate. Carbon disulfide is not a kinetic superdipolarophile with (1,2,3-benzotriazolium-1-yl)aminide 1,3-dipoles. The Royal Society of Chemistry 2000.
- Butler, Richard N.,Wallace, Leonie M.
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p. 4335 - 4338
(2007/10/03)
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- Synthesis and structure-activity relationships of novel phenylcyanoguanidine derivatives as potassium channel openers
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3,5-Di-substituted phenylcyanoguanidine derivatives with halogen, cyano, and/or nitro groups at the 3- and 5-positions of the benzene ring exhibited very strong smooth muscle relaxation activity in vitro, as compared to pinacidil. Among them, N-(3-chloro-5-cyanophenyl)-N'-cyano-N''-tert- pentylguanidine (5s) showed 27-fold more potent activity than pinacidil, and exhibited a stronger and more lasting antihypertensive effect than pinacidil by oral administration to spontaneously hypertensive rats. We propose a new pharmacophore model in which the essential factors for binding to the potassium channel are an NH and a bulky alkyl group.
- Yoshiizumi, Kazuya,Ikeda, Shoji,Goto, Katsumi,Morita, Tominori,Nishimura, Noriyasu,Sukamoto, Takayuki,Yoshino, Kohichiro
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p. 2042 - 2050
(2007/10/03)
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- Some chemistry of 4,5-dichloro-1,2,3-dithiazolium chloride and its derivatives
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4,5-Dichloro-1,2,3-dithiazolium chloride 1 reacts with fluoroanilines (see Table 1) to give the iminodithiazoles 5 in very high yield.Thermolysis of the latter gave the corresponding 2-cyanobenzothiazoles 6 together, in some cases, with the cyanoimidoyl chlorides 7.This reaction sequence provides modest yields of 2-cyanobenzothiazoles from the corresponding aniline, in two steps.Treatment of the iminodithiazoles with m-chloroperbenzoic acid in dichloromethane at or below room temperature opened the heterocyclic ring to give the N-arylcyanothioformamides (e.g. 8 --> 10), except for the p-nitrophenyl compound which gave p-nitrophenyl isothiocyanate 14 in high yield.
- Besson, Thierry,Rees, Charles W.
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p. 1659 - 1662
(2007/10/02)
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- 1,1'-Thiocarbonyldi-2,2'-pyridone. A New Useful Reagent for Functional Group Conversions under Essentially Neutral Conditions
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1,1'-Thiocarbonyldi-2,2'-pyridone is a useful reagent for the preparation of nitriles, carbodiimides, cyclic thionocarbonates, and isothiocyanates and deoxygenation of alcohols under essentially neutral conditions.
- Kim, Sunggak,Yi, Kyu Yang
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p. 2613 - 2615
(2007/10/02)
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- Fragmentation of N-aryl- and N-Aralkyl-N',N"-dicarbomethoxyguanidines with Thiophosgene
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N-Aryl- and N-aralkyl-N',N"-dicarbomethoxyguanidines (3) on treatment with thiophosgene undergo fragmentation to yield N,N'-dicarbomethoxyurea (5) and the isothiocyanates.
- Viswanathan, N.,Sidhaye, A. R.
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p. 659 - 660
(2007/10/02)
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- DI-2-PYRIDYL THIONOCARBONATE. A NEW REAGENT FOR THE PREPARATION OF ISOTHIOCYANATES AND CARBODIIMIDES.
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Reaction of amines with di-2-pyridyl thionocarbonate affords the corresponding isothiocyanates at room temperature, while reaction of N,N'-disubstituted thioureas with di-2-pyridyl thionocarbonate in the presence of 4-dimethylaminopyridine as a catalyst affords the corresponding carbodiimides in high yields.
- Kim, Sunggak,Yi, Kyu Yang
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p. 1661 - 1664
(2007/10/02)
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- Degradation in Aqueous Solution of O-Aryl N-Arylthioncarbamates to Aryloxide Ions and Isothiocyanates. A Study of Leffler's Assumption
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Rate constants for the title reaction have been measured in both forward and reverse directions leading to rates and equilibrium constants for all steps in equation (i).The effects of varying the structures of Ar and Ar' on the equilibrium and rate constants were measured; identical Leffler-Grunwald indices (α=βF/βEQ=d log k/d log K) for the addition step are observed for variation in Ar and Ar' although individual β values are markedly different.Identical α parameters arising from different substituent interaction pathways to a single bond are required if the reaction conforms to the Leffler assumption; on this basis the α parameter is considered a good measure of transition-state structure relative to reactant- and product-states for the addition reaction. 'Effective charges' on the phenolic oxygen in the thioncarbamate and its conjugate base indicate considerable C(1+)-S(1-) character in the formal thioncarbamoyl bond.
- Hill, Stephen V.,Thea, Sergio,Williams, Andrew
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p. 437 - 446
(2007/10/02)
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