- A catalyst-free method for the synthesis of 1,4,2-dithiazoles from isothiocyanates and hydroxylamine triflic acid salts
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A catalyst-free method for the preparation of 1,4,2-dithiazoles is developed by reactions of isothiocyanates with hydroxylamine triflic acid salts. This reaction achieves C-S, C-N, and S-N bond formation, and a range of products are obtained in moderate to good yields. The obvious feature is using shelf-stable hydroxylamine triflic acid salts as a N source to synthesize heterocycles under mild conditions.
- An, Zhenyu,Liu, Yafeng,Ren, Yi,Wang, Ting,Yan, Rulong
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supporting information
p. 6206 - 6209
(2021/07/28)
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- NaOH-promoted one-pot aryl isothiocyanate synthesis under mild benchtop conditions
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In this work, we have established a green synthesis of aryl isothiocyanates promoted by the low-cost and readily available NaOH from aryl amines and carbon disulfide in a one-pot procedure. The developed protocol features no extra desulfurating reagents and mild benchtop conditions, in which NaOH serves as both the base and the desulfurating reagent to decompose the dithiocarbamate intermediate. Fourteen examples of aryl amines bearing electronic neutral, rich and poor substituents, as well as benzylamine, have proved to be compatible substrates in the developed method to furnish the corresponding isothiocyanates. The reaction has been performed on a gram scale to further demonstrate its synthetic utility. Compared to the reported base-promoted synthesis of aryl isothiocyanates that requires the use of special equipment, such as the ball mill or the microwave reactor, the simplicity in operation and scalability enables this method to efficiently access a variety of aryl isothiocyanates.
- Li, Hang,Liu, Xinyun,Yin, Xiaogang
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supporting information
p. 839 - 844
(2021/05/27)
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- Diaryl-substituted thiosemicarbazone: A potent scaffold for the development of New Delhi metallo-β-lactamase-1 inhibitors
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The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has become an emerging public health threat. Inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. A potent scaffold, diaryl-substituted thiosemicarbazone, was constructed and assayed with metallo-β-lactamases (MβLs). The obtained twenty-six molecules specifically inhibited NDM-1 with IC50 0.038–34.7 μM range (except 1e, 2e, and 3d), and 1c is the most potent inhibitor (IC50 = 0.038 μM). The structure-activity relationship of synthetic thiosemicarbazones revealed that the diaryl-substitutes, specifically 2-pyridine and 2-hydroxylbenzene improved inhibitory activities of the inhibitors. The thiosemicarbazones exhibited synergistic antimycobacterial actions against E. coli-NDM-1, resulted a 2–512-fold reduction in MIC of meropenem, while 1c restored 16–256-, 16-, and 2-fold activity of the antibiotic on clinical isolates ECs, K. pneumonia and P. aeruginosa harboring NDM-1, respectively. Also, mice experiments showed that 1c had a synergistic antibacterial ability with meropenem, reduced the bacterial load clinical isolate EC08 in the spleen and liver. This work provided a highly promising scaffold for the development of NDM-1 inhibitors.
- Li, Jia-Qi,Sun, Le-Yun,Jiang, Zhihui,Chen, Cheng,Gao, Han,Chigan, Jia-Zhu,Ding, Huan-Huan,Yang, Ke-Wu
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- Design, synthesis and biological evaluation of novel 2,4-disubstituted quinazoline derivatives targeting H1975 cells via EGFR-PI3K signaling pathway
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In order to find new and highly effective anti-tumor drugs with targeted therapeutic effects, a series of novel 4-aminoquinazoline derivatives containing N-phenylacetamide structure were designed, synthesized and evaluated for antitumor activity against four human cancer cell lines (H1975, PC-3, MDA-MB-231 and MGC-803) using MTT assay. The results showed that the compound 19e had the most potent antiproliferative activity against H1975, PC-3, MDA-MB-231 and MGC-803 cell lines. At the same time, compound 19e could significantly inhibit the colony formation and migration of H1975 cells. Compound 19e also arrested the H1975 cell cycle in the G1 phase and mediated cell apoptosis, promoted the accumulation of ROS in H1975 cells. Furthermore, compound 19e exerted antitumor effect in vitro by reducing the expression of anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic protein Bax and p53. Mechanistically, compound 19e could significantly decreased the phosphorylation of EGFR and its downstream protein PI3K in H1975 cells. Which indicated that compound 19e targeted H1975 cell via interfering with EGFR-PI3K signaling pathway. Molecular docking showed that compound 19e could bind into the active pocket of EGFR. Those work suggested that compound 19e would have remarkable implications for further design of anti-tumor agents.
- Chao, Gao,Dai, Honglin,Ke, Yu,Li, Erdong,Lihong, Shan,Liu, Hongmin,Liu, Limin,Si, Xiaojie,Wang, Zhengjie,Yang, Zhang,Zhang, Luye,Zhang, Qiurong,Zheng, Jiaxin
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- Iron-promoted one-pot approach: Synthesis of isothiocyanates
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We have established a facile and versatile synthesis for the construction of isothiocyanates from their respective amines in the presence of an eco-friendly, inexpensive, easily available Iron catalyst under mild conditions. This reaction provides the target products through the formation of thiocarbamate salt as an intermediate. Both aromatic amines and aliphatic amines provided the respective target products in moderate to high yield under optimized reaction conditions. However, electron withdrawing substituents were difficult to give target product at room temperature, whereas, they obtained final products in good yield at moderate temperature. In addition, mechanistic studies were revealed that the synthetic route involved iron based subsequent reactions of addition and removal of sulfur.
- Pendem, Venkata Bhavanarushi,Nannapaneni, Madhavi
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p. 485 - 490
(2020/02/18)
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- Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions
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Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01–TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 μM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.
- Cheng, Minghui,Meng, Xin,Tang, Haikang,Xu, Wenqing,Yang, Fujun,Zhang, Yuan
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p. 344 - 353
(2019/12/30)
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- Direct, Microwave-Assisted Synthesis of Isothiocyanates
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A microwave-assisted desulfuration of readily available dithiocarbamates, formed in situ from primary amines, leading to target isothiocyanates has been developed. This efficient protocol provides a rapid, environmentally benign route to aliphatic and aromatic isothiocyanates.
- Janczewski, ?ukasz,Gajda, Anna,Gajda, Tadeusz
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supporting information
p. 2528 - 2532
(2019/04/03)
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- Unclicking of thioureas: Base catalyzed elimination of anilines and isothiocyanates from thioureas
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Bisaromatic thioureas are widely used in e.g. asymmetric organocatalysis and considered to be robust compounds. Herein we show, in strong contrast to common notion, that thioureas dissociate to amines and isothiocyanates in a base catalyzed reaction under mild conditions. This ‘unclicking’ process can occur in the presence of weak organic bases even at moderate temperatures. The influence of the substituents at the aromatic rings of the thiourea on the regioselectivity of this unclicking process is also shown.
- Vlatkovi?, Matea,Feringa, Ben L.
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p. 2188 - 2192
(2019/03/05)
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- Synthesis of thiocarbamoyl fluorides and isothiocyanates using CF3SiMe3 and elemental sulfur or AgSCF3 and KBr with amines
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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
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supporting information
p. 2106 - 2110
(2019/03/26)
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- Synthesis methods for isothiocyanate derivative
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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; 0069; 0070; 0071; 0072
(2019/05/22)
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- Na2S2O8-mediated efficient synthesis of isothiocyanates from primary amines in water
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We have developed two green, practical, and efficient procedures, including a one-pot one, to synthesize isothiocyanates from amines and carbon disulfide via desulfurization with sodium persulfate. Water is used as the solvent. Basic conditions are necessary for good chemoselectivity for isothiocyanates. Structurally diverse linear and branched alkyl amines and aryl amines are readily converted to isothiocyanates by the two procedures in satisfactory yields. Halogens, benzylic C-H bonds, methylthio, nitro, ester, alkenyl, electron-rich or -deficient (hetero)aryls, acetylenyl, and even phenolic and alcoholic hydroxyls are well tolerated. The one-pot procedure in water can also be used to realize the preparation of chiral isothiocyanates from chiral amines, and the modification of bioactive structures with free amino groups. In large-scale preparation, simple and practical purification procedures independent of column chromatography are developed.
- Fu, Zhicheng,Yuan, Wenhao,Chen, Ning,Yang, Zhanhui,Xu, Jiaxi
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supporting information
p. 4484 - 4491
(2018/10/17)
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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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- One-pot three-component tandem reaction: Synthesis of aryl/alkyl cyanamides libraries and their further conversion into tetrazole derivatives
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We have developed methodology for the synthesis of aryl/alkyl cyanamides from amines in one-pot four steps reaction using cheap, readily available and air stable copper source as catalyst under mild reaction conditions. We have also studied the application of cyanamides. In this connection, we could construct aryl tetrazolamine from cyanamides using click reaction.
- Mandapati, Usharani,Mandapati, Pavan,Pinapati, Srinivasarao,Tamminana, Ramana,Rudraraju, Rameshraju
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supporting information
p. 500 - 510
(2018/02/06)
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- Copper promoted desulfurization towards the synthesis of isothiocyanates
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The cheap, readily available and air stable catalyst was used as the desulfurization agent for the conversion of aniline to isothiocyanates in one pot two step reaction under mild reaction conditions.
- Mandapati, UshaRani,Pinapati, Srinivasarao,Rudraraju, RameshRaju
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p. 125 - 128
(2016/12/26)
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- Cobalt mediated by desulfurization toward the synthesis of isothiocyanates
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A highly efficient and simple protocol for the construction of aromatic and aliphatic isothiocyanates from their respective amines in the presence of cheap, readily available, and air-stable cobalt catalyst is described. All reactions were carried out under optimized reaction conditions and gave target products in good to excellent yields within shorter reaction time.
- Seelam, Mohan,Shaik, Bajivali,Kammela, Prasada Rao
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supporting information
p. 1759 - 1765
(2016/10/31)
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- A metal-free synthesis of 2-aminobenzothiazoles through aminyl radical addition to aryl isothiocyanates
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A convenient synthesis of 2-aminobenzothiazoles, starting from aryl isothiocyanates and formamides under metal-free conditions, is described. Various secondary and tertiary amine- and even α-amino acid-derived formamides can be used as amino sources in this process. Mechanistic studies suggest that the reaction is initiated by decarbonylative aminyl radical formation in the presence of n-Bu4NI and TBHP, followed by aminyl radical addition to isothiocyanates and cyclization via sulfur centred radical intermediates.
- He, Yimiao,Li, Jing,Luo, Shuang,Huang, Jinbo,Zhu, Qiang
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supporting information
p. 8444 - 8447
(2016/07/07)
-
- Synthesis of 4-phenylthieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine-5 (4H)-one derivatives and evaluation of their anti-inflammatory activity
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A series of 4-phenylthieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine-5 (4H)-ones (5a-p) with triazole or other heterocyclic substituents (6-11) was synthesized and the compounds were evaluated for their anti-inflammatory activity using the xylene-induced ear-edema test. Pharmacological analyses showed that the compound 4- (4-chlorophenyl)thieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine- 5 (4H)-one (5m) exhibited the greatest anti-inflammatory activity (50.48% inhibition, 30 min after intraperitoneal administration) and was more potent than the reference drug, indomethacin. The peak activity of 5m was observed 4 h after oral administration, and it showed a higher anti-inflammatory activity than indomethacin did at a dose of 100 mg/kg.
- Pan, Fu-Jun,Wang, Shi-Ben,Liu, Da-Chuan,Gong, Guo-Hua,Quan, Zhe-Shan
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p. 141 - 148
(2016/03/12)
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- An efficient methodology for the synthesis of thioureas from amine mediated by a cobalt source
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The cheap, readily available and air stable cobalt catalyst was used as the desulfurization agent for the conversion of aniline to thioureas in one pot three step reaction under mild reaction conditions. The reactions are rapid and facile and accomplished at room temperature.
- Seelam, Mohan,Shaikh, Baji Vali,Tamminana, Ramana,Kammela, Prasada Rao
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supporting information
p. 5297 - 5300
(2016/11/11)
-
- NOVEL FLAVONE BASED EGFR INHIBITORS AND PROCESS FOR PREPARATION THEREOF
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The present invention discloses a novel EGFR inhibitor compound of formula (1), process for preparation thereof and methods of treating abnormal cell growth in mammals by administering the compounds of formula (1). wherein, R is selected from hydrogen, alkyl, nitro, halogens such as chlorine, bromine, fluorine and iodine; Rl= hydrogen, alkyl, alkoxy, aryl, nitro, halogens such as chlorine, bromine, fluorine and iodine, trifluoromethyl, thioalkyl, trifluromethoxy, trialkylsilyl.
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Page/Page column 13; 14
(2016/09/22)
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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.
-
supporting information
p. 1613 - 1619
(2013/10/22)
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- Chloroarylation and thiocyanatoarylation of itaconic acid
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Under conditions of Meerwein reaction and anionarylation the aryldiazonium salts and itaconic acid form 2-chloro(thiocyanato)-2-benzylbutanedioic acids as the chloro- and thiocyianatoarylation products. The reaction is not accompanied by the decarboxylati
- Baranovskii,Petrushka,Fesak,Grishchuk
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p. 325 - 328
(2013/08/15)
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- 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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- Synthesis and fungicidal activities of some 2-substituted arylamino-5-(2′-furyl)-1,3,4-thiadiazolo[3,2-c]thiazoles and 5-substituted aryl-2-substituted arylamino-1,3,4-thiadiazolo[3,2-c]thiazoles
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Several 2-substituted arylamino-5-(2′-furyl)-1,3,4-thiadiazolo[3,2-c] thiazoles have been synthesised by cyclisation of 3-substituted aryl thiocarbanilido-2-(2′-furyl)thiazolidin-4-ones with cone. H 2SO4 with constant stirring in cold and 5-substituted aryl-2-substituted arylamino-1,3,4-thiadiazolo[3,2-c]thiazoles have been synthesised by the cyclisation of 2-substituted aryl-3-substituted arylthiourido-thiazolidin-4-ones with cone. H2SO4 with constant stirring in cold and screened for their antifungal activities against Helminthosporium oryzae and Cephalosporium sacchari.
- Tiwari, Shailendra,Nizamuddin
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p. 679 - 683
(2013/07/26)
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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)
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- A diversified assembly of 1,2,4-oxadiazol-3-amines: Metallic thiophile catalyzed chemoselective one-pot reaction of aryl isothiocyanates, amidines/guanidines, and hydroxylamine
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An efficient one-pot synthesis of 1,2,4-oxadiazol-3-amines from simple starting materials, isothiocyanates, amidines/guanidines, and hydroxylamine, is described. The reaction is facilitated by metallic-thiophile-assisted desulfurization of in situ formed amidino- or guanidinothiourea to give chemoselectively N-hydroxyguanidine intermediates that give exclusively various 1,2,4-oxadiazol-3-amines in good to excellent yields. The reaction mechanistic pathway may proceed through an intramolecular 5-exo-trig cyclization.
- Jalani, Hitesh B.,Sudarsanam, V.,Vasu, Kamala K.
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p. 3378 - 3386,9
(2012/12/12)
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- A new convenient synthesis of 5-aryl-2-(arylamino)-1,3,4-oxadiazole derivatives
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Electrical energy offers numerous benefits for conducting a synthesis, including increased reaction rates, yield enhancements and cleaner chemistries. 5-Aryl-2-(arylamino)-1,3,4-oxadiazoles were synthesised directly from acylthiosemicarbazide on the platinum electrode under controlled potential electrolysis in an undivided cell assembly in acetonitrile.
- Kumar, Sanjeev
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p. 216 - 220
(2015/03/03)
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- Isatin-β-thiosemicarbazones as potent herpes simplex virus inhibitors
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A series of isatin-β-thiosemicarbazones have been designed and evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in a plaque reduction assay. Their cytotoxicity was examined using human rhabdomyosarcoma cells (RD cells). Several derivatives of isatin-β-thiosemicarbazone exhibited significant and selective antiviral activity with low cytotoxicity. It was found that the thiourea group at thiosemicarbazone and the NH functionality at isatin were essential for their antiherpetic activity. The synthesis and structure-activity relationship studies are presented.
- Kang, Iou-Jiun,Wang, Li-Wen,Hsu, Tsu-An,Yueh, Andrew,Lee, Chung-Chi,Lee, Yen-Chun,Lee, Ching-Yin,Chao, Yu-Sheng,Shih, Shin-Ru,Chern, Jyh-Haur
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scheme or table
p. 1948 - 1952
(2011/05/04)
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- Synthesis and biological evaluation of dihydroisoquinoline-2(1H)- carbothioamide derivatives as TRPV1 antagonists
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TRPV1 receptor is an important analgesia target. Its antagonists are expected to prevent pain perception by blocking the receptor directly. In this letter, eight dihydroisoquinoline-2(1H)-carbothioamide derivatives were designed and synthesized as TRPV1 antagonists. The benzene ring was modified with different substitutional groups. Preliminary biological tests suggested that the new compounds exhibited TRPV1 antagonist activity and different analgesia effects, some of which were promising as analgesia drugs.
- Qian, Hai,Chen, Wei,Zhang, Xiaoyan,Zhang, Huibin,Zhou, Jinpei,Huang, Wenlong,Jin,Dai, Dongyan
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p. 235 - 237
(2011/03/18)
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- Discovery of dual inhibitors targeting both HIV-1 capsid and human cyclophilin A to inhibit the assembly and uncoating of the viral capsid
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HIV-1 assembly and disassembly (uncoating) processes are critical for the HIV-1 replication. HIV-1 capsid (CA) and human cyclophilin A (CypA) play essential roles in these processes. We designed and synthesized a series of thiourea compounds as HIV-1 assembly and disassembly dual inhibitors targeting both HIV-1 CA protein and human CypA. The SIV-induced syncytium antiviral evaluation indicated that all of the inhibitors displayed antiviral activities in SIV-infected CEM cells at the concentration of 0.6-15.8 μM for 50% of maximum effective rate. Their abilities to bind CA and CypA were determined by ultraviolet spectroscopic analysis, fluorescence binding affinity and PPIase inhibition assay. Assembly studies in vitro demonstrated that the compounds could potently disrupt CA assembly with a dose-dependent manner. All of these molecules could bind CypA with binding affinities (Kd values) of 51.0-512.8 μM. Fifteen of the CypA binding compounds showed potent PPIase inhibitory activities (IC50 values 1 μM) while they could not bind either to HIV-1 Protease or to HIV-1 Integrase in the enzyme assays. These results suggested that 15 compounds could block HIV-1 replication by inhibiting the PPIase activity of CypA to interfere with capsid disassembly and disrupting CA assembly.
- Li, Jiebo,Tan, Zhiwu,Tang, Shixing,Hewlett, Indira,Pang, Ruifang,He, Meizi,He, Shanshan,Tian, Baohe,Chen, Kan,Yang, Ming
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scheme or table
p. 3177 - 3188
(2009/09/05)
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- Triphosgene: An efficient catalyst for synthesis of isothiocyanates
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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
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p. 1972 - 1975
(2008/09/21)
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- Highly potent, water soluble benzimidazole antagonist for activated α4β1 integrin
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The cell surface receptor α4β1 integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety, resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC50 = 305 pM]. With exceptional solubility, this finding has the potential for improving PK to help diagnose and treat lymphomas.
- Carpenter, Richard D.,Andrei, Mirela,Lau, Edmond Y.,Lightstone, Felice C.,Liu, Ruiwu,Lam, Kit S.,Kurth, Mark J.
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p. 5863 - 5867
(2008/04/05)
-
- 2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 1: Discovery of CB2 receptor selective compounds
-
2-Arylimino-5,6-dihydro-4H-1,3-thiazines have been identified as a novel class of cannabinoid agonists. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of potent agonists of CB2 receptor. The most potent compound 13 displays Ki values of >5000 and 9 nM to CB1 and CB2 receptors, respectively.
- Kai, Hiroyuki,Morioka, Yasuhide,Murashi, Takami,Morita, Koichi,Shinonome, Satomi,Nakazato, Hitoshi,Kawamoto, Keiko,Hanasaki, Kohji,Takahashi, Fumiyo,Mihara, Shin-ichi,Arai, Tohko,Abe, Kohji,Okabe, Hiroshi,Baba, Takahiko,Yoshikawa, Takayoshi,Takenaka, Hideyuki
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p. 4030 - 4034
(2008/02/08)
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- Isothiocyanates from tosyl chloride mediated decomposition of in situ generated dithiocarbamic acid salts
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(Chemical Equation Presented) A facile and general protocol for the preparation of isothiocyanates from alkyl and aryl amines is reported. This method relies on a tosyl chloride mediated decomposition of a dithiocarbamate salt that is generated in situ by treatment of an amine with carbon disulfide and triethylamine. Utilizing this protocol, we have prepared 19-alkyl- and arylisothiocyanates in moderate to excellent yield.
- Wong, Rince,Dolman, Sarah J.
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p. 3969 - 3971
(2008/02/01)
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- A new method for the synthesis of isothiocyanates from dithiocarbamates or alkyl amines using chlorosilanes as decomposition reagents
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A series of isothiocyanates were prepared in good yields by the decomposition of dithiocarbamates using chlorosilanes such as Me 3SiCl, Me2SiCl2, MeSiCl3, and SiCl4 as decomposition reagents. Alkyl isothiocyanates were obtained by a facile one-pot method in high yield from alkyl amines using these inexpensive decomposition reagents in the presence of a base. Copyright Taylor & Francis Group, LLC.
- Bian, Gaofeng,Qiu, Huayu,Jiang, Jianxiong,Wu, Jirong,Lai, Guoqiao
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p. 503 - 508
(2007/10/03)
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- Use of tetramethylthiuram disulfide in synthesis of nitrogen-containing heterocyclic compounds
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We have developed a method for synthesis of aryl isothiocyanates by means of thiocarbamoylation of aromatic amines by tetramethylthiuram disulfide followed by degradation of the intermediate N(1)-aryl-N,N- dimethylthiourea by concentrated HCl. We have shown that thiocarbamoylation of 4-amino-5-ethyl-4H-1,2,4-triazole-3-thiol occurs at the 2 position of the triazole ring, while thiocarbamoylation of 4-amino-3-methyl-6-phenyl-4,5- dihydro-1,2,4-triazin-5-one leads to the dihetaryl-substituted thiourea. We consider the possibility of using N(1)-aryl-N,N-dimethylthioureas as analogs of isothiocyanates in reactions with N-nucleophiles. 2005 Springer Science+Business Media, Inc.
- Demchenko,Yanchenko,Kisly,Lozinskii
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p. 668 - 672
(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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- Thiocyanatoarylation of α,β,β-Trifluorostyrene
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Reactions of α,β,β-trifluorostyrene with arenediazonium tetrafluoroborates and potassium thiocyanate result in addition of the aryl and thiocyanato group across the double bond. Unlike other related reactions, the process requires no catalyst. The reaction is accompanied by formation of aryl thiocyanates and aryl isothiocyanates as by-products.
- Bilaya,Obushak,Ganushchak
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p. 995 - 998
(2007/10/03)
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- A general synthesis of isothiocyanates from dithiocarbamates using claycop
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A Convenient and simple synthesis of alkyl, aryl and amino acid isothiocyanates is described by the decomposition of ammonium dithiocarbamates using Claycop in mild conditions.
- Mesheram, Harashadas M.,Dale, Srinivas,Yadav
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p. 8743 - 8744
(2007/10/03)
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- Synthesis and Reaction of 2-Imino-1,3-thiazetidines and 2-Imino-1,3-dithietanes
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2-Imino-1,3-thiazetidines and 2-imino-1,3-dithietanes were synthesized and their reactivities were studied.The former readily underwent ring-opening reaction with amines to yield guanidine derivatives.The reaction products were applied to the synthesis of heterocycles such as triazoles and triazines.The latter was converted to isothiocyanate by the reaction of m-chloroperbenzoic acid.
- Okajima, Nobuyuki,Okada, Yoshiyuki
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p. 177 - 185
(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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- Synthesis and Identification of 4-Methyl-N-(4H-1,2,4-triazol-4-yl)-2-benzothiazolamine, an Impurity in the Synthesis of Tricyclazole
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The synthesis of 4-methyl-N-(4H-1,2,4-triazol-4-yl)-2-benzothiazolamine, 4, a by-product in the synthesis of tricyclazole, 1, by oxidative cyclization of the corresponding thiourea, 12, with thionyl chloride, is described.
- Dreikorn, Barry A.,Unger, Paul
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p. 1735 - 1737
(2007/10/02)
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- A NOVEL SYNTHESIS OF FLUORINATED PYRIDO PYRIMIDINE DERIVATIVES
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Fluorinated 4-imino-3,5,7-trisubstituted-pyrido pyrimidine-2(1H)thiones have been synthesised in good yields by the reaction of 2-amino-3-cyano-4,6-disubstituted-pyridines with various arylisothiocyanates.These new type of products have been characterised by elemental analysis, IR, 1H and 19F NMR spectral studies.
- Prakash, L.,Verma, S. S.,Shaihla,Tyagi, Erra,Mital, R. L.
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p. 303 - 310
(2007/10/02)
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- 1H and 13C NMR Studies on 3-Aryl-2-thioxo-4-oxazolidinones and 3-Arylrhodanines
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3-Aryl-2-thioxo-4-oxazolidinones and 3-arylrhodanines have been studied for magnetic non-equivalence of diastereotopically related proton and 13C nuclei in rotational isomers, and for steric interactions between the aryl and heterocyclic moieties of these compounds.For the majority of rotational isomers the barriers to internal rotation about the aryl C-N bond were >100 kJ mol-1, due to the steric bulk of the thiocarbonyl group.Chemical isolation of several of the diastereomers was achieved.The enhanced steric effect and the difference in the electronic effect of the sulphur atom in relation to the oxygen atom appeared to have no influence on the small chemical shift differences of the rotational isomers, detected for some 1H and some 13C nuclei.
- Aksac, Zihni,Pinar, Esat,Icli, Siddik
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p. 548 - 551
(2007/10/02)
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