- 4-PHENYL-N-(PHENYL)THIAZOL-2-AMINE DERIVATIVES AND RELATED COMPOUNDS AS ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS FOR THE TREATMENT OF E.G. ANGIOGENESIS IMPLICATED OR INFLAMMATORY DISORDERS
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4-phenyl-N-(phenyl)thiazol-2-amine and 4-(pyridin-3-yl)-N-( phenyl) thiazol-2-amine derivatives and the corresponding thiadiazole, thiophene, oxazole, oxadiazole, imidazole and triazole derivatives and related compounds as aryl hydrocarbon receptor (AHR) agonists for the treatment of angiogenesis implicated disorders, such as e.g. retinopathy, psoriasis, rheumatoid arthritis, obesity and cancer, or inflammatory disorders.
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Paragraph 00221; 00311
(2021/06/26)
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- Design and synthesis of novel N-[3-(benzimidazol-2-ylamino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives as potential anticancer agents
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In this contribution, we report the design, synthesis and cytotoxicity studies of a series of N-[3-(benzimidazol-2-yl-amino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives. In vitro cytotoxicity assay of 26 selected compounds was carried out at National Cancer Institute (NCI), USA. Out of them, compounds 10e (NSC D-762842/1) and 11s (NSC D-764942/1) have shown remarkable cytotoxicity with GI50 values ranging between “0.589–14.3?μM” and “0.276–12.3?μM,” respectively, in the representative nine subpanels of human tumor cell lines. Further, flow cytometry analysis demonstrated that compound 10e exerted cell cycle arrest at G2/M phase and showed dose-dependent enhancement in apoptosis in K-562 leukemia cancer cells.
- Kumar, Honnavalli Yogish,Murumkar, Prashant R.,Pawar, Vijay,Srinivasan, B. P.,Yadav, M. R.
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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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- N-Trifluoromethyl Hydrazines, Indoles and Their Derivatives
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Reported herein is the first efficient strategy to synthesize a broad range of unsymmetrical N-CF3 hydrazines, which served as platform to unlock numerous currently inaccessible derivatives, such as tri- and tetra-substituted N-CF3 hydrazines, hydrazones, sulfonyl hydrazines, and valuable N-CF3 indoles. These compounds proved to be remarkably robust, being compatible with acids, bases, and a wide range of synthetic manipulations. The feasibility of RN(CF3)-NH2 to function as a directing group in C?H functionalization is also showcased.
- Bouayad-Gervais, Samir,Scattolin, Thomas,Schoenebeck, Franziska
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supporting information
p. 11908 - 11912
(2020/05/18)
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- Discovery and optimization of 4-oxo-2-thioxo-thiazolidinones as NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inhibitors
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Aberrant activation of NLRP3 inflammasome is present in a subset of acute and chronic inflammatory diseases. The NLRP3 inflammasome has been recognized as an attractive therapeutic target for developing novel and specific anti-inflammatory inhibitors. Cellular structure-activity relationship-guided optimization resulted in the identification of 4-oxo-2-thioxo-thiazolidinone derivative 9 as a selective and direct small-molecule inhibitor of NLRP3 with IC50 of 2.4 μM, possessing favorable ex vivo and in vivo pharmacokinetic properties. Compound 9 may represent a lead for the development of anti-inflammatory therapeutics for treating NLRP3-driven diseases.
- Chen, Yun,Deng, Xianming,He, Hongbin,Hu, Zhiyu,Huang, Huiying,Jiang, Hua,Li, Li,Xu, Qingyan,Zhou, Rongbin
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supporting information
(2020/02/15)
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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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- 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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p. 4484 - 4491
(2018/10/17)
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- Inhibitors of the Diadenosine Tetraphosphate Phosphorylase Rv2613c of Mycobacterium tuberculosis
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The intracellular concentration of diadenosine tetraphospate (Ap4A) increases upon exposure to stress conditions. Despite being discovered over 50 years ago, the cellular functions of Ap4A are still enigmatic. If and how the varied Ap4A is a signal and involved in the signaling pathways leading to an appropriate cellular response remain to be discovered. Because the turnover of Ap4A by Ap4A cleaving enzymes is rapid, small molecule inhibitors for these enzymes would provide tools for the more detailed study of the role of Ap4A. Here, we describe the development of a high-throughput screening assay based on a fluorogenic Ap4A substrate for the identification and optimization of small molecule inhibitors for Ap4A cleaving enzymes. As proof-of-concept we screened a library of over 42, 000 compounds toward their inhibitory activity against the Ap4A phosphorylase (Rv2613c) of Mycobacterium tuberculosis (Mtb). A sulfanylacrylonitril derivative with an IC50 of 260 ± 50 nM in vitro was identified. Multiple derivatives were synthesized to further optimize their properties with respect to their in vitro IC50 values and their cytotoxicity against human cells (HeLa). In addition, we selected two hits to study their antimycobacterial activity against virulent Mtb to show that they might be candidates for further development of antimycobacterial agents against multidrug-resistant Mtb.
- G?tz, Kathrin H.,Hacker, Stephan M.,Mayer, Daniel,Dürig, Jan-Niklas,Stenger, Steffen,Marx, Andreas
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p. 2682 - 2689
(2017/10/27)
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- A novel one-pot synthesis of isothiocyanates and cyanamides from dithiocarbamate salts using environmentally benign reagent tetrapropylammonium tribromide
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A highly efficient and simple protocol for the synthesis of isothiocyanates and cyanamides from their respective amines in the presence of a mild, efficient, and non-toxic reagent tetrapropylammonium tribromide is described. High environmental acceptability of the reagents, cost effectiveness and high yields are the important attributes of this methodology.
- Kuotsu, Neivotsonuo Bernadette,Jamir, Latonglila,Phucho, Tovishe,Sinha, Upasana Bora
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p. 832 - 841
(2018/01/17)
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- Terminal functionalized thiourea-containing dipeptides as multidrug-resistance reversers that target 20S proteasome and cell proliferation
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A series of inhibitors of 20S proteasome based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for inhibition of 20S proteasome and the effects of multidrug-resistance reversers. These compounds exhibited significant selectivity to the β5-subunit of the human 20S proteasome with IC50values at submicromolar concentrations. A docking study of the most active compound 6i revealed key interactions between 6i and the active site of the 20S proteasome in which the thiourea moiety and a nitro group were important for improving activity. In particular, compound 6i appeared to be the most potent compound against the NCI-H460 cell line, and displayed similar efficiency in drug-sensitive versus drug-resistant cancer cell lines, at least partly, by inhibition of the activity of 20S proteasome and induce apoptosis. In addition, 6i-induced apoptosis was significantly facilitated in NCI-H460/DOX cells that had been pretreated with inhibitors of P-gp. Mechanistically, compound 6i might trigger apoptotic signalling pathway. Thus, we conclude that dipeptide derivatives containing the thiourea moiety may be the potential inhibitors of proteasome with the ability to reverse multidrug resistance.
- Qin, Jian-Mei,Huang, Ri-Zhen,Yao, Gui-Yang,Liao, Zhi-Xin,Pan, Ying-Ming,Wang, Heng-Shan
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p. 259 - 269
(2016/12/02)
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- Synthesis and biological evaluation of terminal functionalized thiourea-containing dipeptides as antitumor agents
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A series of antitumor agents based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for antiproliferative activity using a panel of cancer cell lines, and the effects and mechanism of apoptosis induction were determined. These compounds exhibited significant selectivity to different cancer cell lines with IC50 values at micromolar concentrations. In particular, compound I-11 appeared to be the most potent compound, with an IC50 = 4.85 ± 1.44 μM against the NCI-H460 cell line, at least partly, by the induction of apoptosis. Mechanistically, compound I-11 induced the activation of caspase-12 and CHOP, which triggered apoptotic signalling via the ROS-dependent endoplasmic reticulum pathway and arrested the cell cycle at the S phase. Thus, we concluded that dipeptide derivatives containing the thiourea moiety terminally functionalized by electron-withdrawing substituents may be potential antitumor agents for further investigation.
- Huang, Ri-Zhen,Zhang, Bin,Huang, Xiao-Chao,Liang, Gui-Bin,Qin, Jian-Mei,Pan, Ying-Ming,Liao, Zhi-Xin,Wang, Heng-Shan
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p. 8866 - 8878
(2017/02/10)
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- Double three bromo 1,3-di-pyridine salt-based propane and its preparation method, method of use, recovery method and application
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The invention discloses a double tribromo 1,3-bipyridine onium salt dimethylmethane, and a preparation method, an application method, a recovery method and application thereof. The preparation method comprises the following steps: dissolving 1,3-bipyridine onium salt dimethylmethane by using water, and then adding potassium bromide; adding potassium peroxymonosulfate sulfate compound brine solution to prepare a clear solution after dissolving potassium bromide, and then stirring and reacting at -10 to 0 DEG C until solid is separated out; separating out solid, so as to obtain the double tribromo 1,3-bipyridine onium salt dimethylmethane. The product can be used for preparing isothiocyanate, aromatic thiourea or acetanilide. The preparation method disclosed by the invention is mild in condition, and simple to operate the reaction process, and raw materials are easily available. The double tribromo 1,3-bipyridine onium salt dimethylmethane not only can be used as a brominating reagent, but also can be used as organic synthesis intermediates, meanwhile, the reaction efficiency is improved, and the double tribromo 1,3-bipyridine onium salt dimethylmethane is convenient to recover and can be recycled.
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Paragraph 0212; 0213; 0214
(2016/10/07)
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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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- Benzothiazoles: Search for anticancer agents
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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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- Structural optimization and structure-activity relationships of N 2-(4-(4-methylpiperazin-1-yl)phenyl)- N 8-phenyl-9 H -purine-2,8-diamine derivatives, a new class of reversible kinase inhibitors targeting both EGFR-activating and resistance mutations
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This paper describe the structural optimization of a hit compound, N 2-(4-(4-methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine- 2,8-diamine (1), which is a reversible kinase inhibitor targeting both EGFR-activating and drug-resistance (T790M) mutations but has poor binding affinity. Structure-activity relationship studies led to the identification of 9-cyclopentyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)-N 8-phenyl-9H-purine-2,8-diamine (9e) that exhibits significant in vitro antitumor potency against the non-small-cell lung cancer (NSCLC) cell lines HCC827 and H1975, which harbor EGFR-activating and drug-resistance mutations, respectively. Compound 9e was further assessed for potency and selectivity in enzymatic assays and in vivo anti-NSCLC studies. The results indicated that compound 9e is a highly potent kinase inhibitor against both EGFR-activating and resistance mutations and has good kinase spectrum selectivity across the kinome. In vivo, oral administration of compound 9e at a dose of 5 mg/kg caused rapid and complete tumor regression in a HCC827 xenograft model, and an oral dose of 50 mg/kg initiated a considerable antitumor effect in an H1975 xenograft model.
- Yang, Jiao,Wang, Li-Jiao,Liu, Jing-Jing,Zhong, Lei,Zheng, Ren-Lin,Xu, Yong,Ji, Pan,Zhang, Chun-Hui,Wang, Wen-Jing,Lin, Xing-Dong,Li, Lin-Li,Wei, Yu-Quan,Yang, Sheng-Yong
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p. 10685 - 10699
(2013/02/22)
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- Environmentally benign one-pot synthesis of cyanamides from dithiocarbamates using I2 and H2O2
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An environmentally benign reaction is devised for the synthesis of cyanamides from dithiocarbamate salts using iodine and H2O 2. Taylor & Francis Group, LLC.
- Jamir, Latonglila,Sinha, Upasana Bora,Nath, Jayashree,Patel, Bhisma K.
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experimental part
p. 951 - 958
(2012/02/01)
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- Synthesis and reactivity studies of a new reagent, ethyltriphenylphosphonium tribromide
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A new reagent, ethyltriphenyl phosphonium tribromide (ETPPTB), has been synthesized and studied. Results show that the reagent is quite efficient for various reactions such as organic bominations, acylations, and isothiocyanate preparation. Copyright
- Jamir, Latonglila,Alimenla,Kumar, Anil,Sinha, Dipak,Sinha, Upasana B.
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p. 147 - 155
(2011/03/17)
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- A highly efficient methodology for 5-methyl-3-aryl-2-thiooxazolidin-4-ones using lithium perchlorate in DIPEA mediated synthesis
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(Chemical Equation Presented) An efficient methodology for the synthesis of 5-methyl-3-aryl-2-thiooxazolidin-4-ones from aryl isothiocyanates has been developed. Aryl isothiocyanates, synthesized from various anilines, were converted to the desired compounds by treating with ethyl lactate in presence of DIPEA and catalytic amount of lithium perchlorate. This method provides a convenient and cost-effective strategy, with no specific purification protocol.
- Khatik, Gopal L.,Pal, Anang,Apsunde, Tushar D.,Nair, Vipin A.
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experimental part
p. 734 - 739
(2010/08/22)
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- Lithium perchlorate-induced electrophilic activation: one-pot synthesis of 3-aryl-2-thioxotetrahydropyrimidin-4-one derivatives from aryl isothiocyanates
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A novel methodology for the synthesis of N-substituted-3-aryl-2-thioxotetrahydropyrimidin-4(1H)-one derivatives had been developed by the condensation of aryl isothiocyanates with β-amino esters using lithium perchlorate as a catalyst and triethylamine as a base. This strategy not only overcomes the disadvantages of the reported methods but also provides high yield of the product in short span of time by an easily workable procedure.
- Kumar, Varun,Nair, Vipin A.
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body text
p. 966 - 969
(2010/04/29)
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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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- The thiocarbonyl 'S' is softer than thiolate 'S': A catalyst-free one-pot synthesis of isothiocyanates in water
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Treatment of the preformed or the in situ generated aryl/alkyl dithiocarbamates triethylammonium salt (ArNHCSS-.Et 3NH+) with methyl acrylate in an aqueous medium gave solely arylisothiocyanate (ArNCS), whereas the in situ generated aryl dithiocarbamic acid (ArNHCSS-.H+) yielded exclusively the thia-Michael adduct (ArNHCSSCH2CH2COOMe). This differential reactivity can be explained by two alternative mechanisms which is dependent both on the nature of the counter cation and on the pH of the reaction medium. Irrespective of the counter cations, the thiocarbonyl sulfur (=S) atom, having large orbital-coefficient, is softer compared to the thiol/thiolate sulfur (-SH/S-) in a dithiocarbamate salt and the former adds to the Michael acceptor by a 1,4-addition.
- Jamir, Latonglila,Ali, Abdur Rezzak,Ghosh, Harisadhan,Chipem, Francis A. S.,Patel, Bhisma K.
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experimental part
p. 1674 - 1678
(2010/07/04)
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- Efficient preparation of isothiocyanates from dithiocarbamates using bromineless brominating reagent
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For the first time, the crystal structure of a ditribromide reagent 1,1'-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) has been determined. Utilizing this thiophilic bromineless brominating agent EDPBT, highly useful synthetic intermediates (alkyl and aryl isothiocyanates) have been achieved directly from dithiocarbamates. EDPBT can be easily prepared from readily available reagents. It has been used as a thiophilic reagent, and its thiophilicity dominates over its brominating ability for substrates amenable to bromination. This is a sustainable process for the preparation of isothiocyantes because the spent reagent can be recovered, regenerated, and reused. Copyright Taylor & Francis Group, LLC.
- Yella, Ramesh,Ghosh, Harisadhan,Murru, Siva,Sahoo, Santosh K.,Patel, Bhisma K.
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experimental part
p. 2083 - 2096
(2010/08/19)
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- Molecular iodine mediated preparation of isothiocyanates from dithiocarbamic acid salts
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We have developed a general economical and environmentally benign method for the preparation of isothiocyanates from the corresponding dilhiocarbamic acid salts by using cheap and readily available reagent molecular iodine. This is perhaps the most efficient method reported so far for the synthesis of isothiocyanates. The reagent is easily available and nontoxic, and the precipitated sulfur can be removed easily; hence, this method is most suitable for large-scale synthesis. Wiley-VCH Verlag GmbH & Co. KGaA.
- Nath, Jayashree,Ghosh, Harisadhan,Yella, Mamesh,Patel, Bhisma K.
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experimental part
p. 1849 - 1851
(2009/08/07)
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- A one-pot preparation of cyanamide from dithiocarbamate using molecular iodine
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An efficient one-pot method for the synthesis of cyanamides from dithiocarbamate salts via a double desulfurization strategy using molecular iodine is disclosed. Dithiocarbamates, by the action of iodine yield isothiocyanates in situ, which on treatment with aqueous NH3 give thioureas. The thioureas so generated undergo further oxidative desulfurization with I2 giving corresponding cyanamides in good yields. Environmental benignity, cost effectiveness and high yields are the important attributes of this one pot procedure. The Royal Society of Chemistry 2009.
- Nath, Jayashree,Patel, Bhisma K.,Jamir, Latonglila,Sinha, Upasana Bora,Satyanarayana
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experimental part
p. 1503 - 1506
(2010/05/18)
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- Desulfurization mediated by hypervalent iodine(III): A novel strategy for the construction of heterocycles
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The desulfurization ability of diacetoxyiodobenzene (DIB) has been explored in the preparation of isothiocyanates from the corresponding dithiocarbamate salts. The in situ generated isothiocyanates reacted with o-phenylenediamine and o-aminophenol to form monothioureas, which, on treatment with a further equivalent of DIB in one pot, gave benzimidazoles and aminobenzoxazoles, respectively. Aliphatic 1,2-diamines on reaction with 2 equiv. of isothiocyanate followed by treatment with DIB gave imidazolidenecarbothioamides, whereas the treatment of aromatic 1,2-diaminebis(thioureas) yielded benzimidazoles with the concurrent formation of isothiocyanate. The driving force for the formation of the latter is the aromatization of the product. The use of DIB makes these methods simpler and more efficient, giving high yields of the desired products in one pot. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Ghosh, Harisadhan,Yella, Ramesh,Nath, Jayashree,Patel, Bhisma K.
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scheme or table
p. 6189 - 6196
(2009/05/27)
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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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- Experimental and Theoretical Studies of Substituent Effects in Hydrogen Bond Based Molecular Recognition of a Zwitterion by Substituted Arylureas
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Electron withdrawing groups have a strong effect on hydrogen bonding to aryl ureas.The effect of para substituents modestly exceeds the effect of meta substituents.Among common substituent parameters, ?- (ρ = 1.77, r2 = 0.988) is found to be the best predictor for the observed effects of para substituents in aryl ureas.Semi-empirical and ab initio methods are used to calculate charge distributions in substituted benzene derivatives and in these ureas.A comparison of experimental and predicted (AM1, STO3G, 321-G*, 631-G**) dipole moments of benzene derivatives is presented.It is shown that calculated surface electric potentials for these thioureas succesfully predict the relative hydrogen bonded association energies.
- Wilcox, Craig S.,Kim, Eun-il,Romano, David,Kuo, Lung Huang,Burt, Arthur L.,Curran, Dennis P.
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p. 621 - 634
(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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- Synthesis of Substituted Thiocarboxamides, Carboxamides and Thioureas as Potential Anthelmintic and Antimicrobial Agents
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A series of substituted thiocarboxamides (6-26), carboxamides (27-32), thioureas (33-37) and urea (38) have been synthesized starting from various aryl isothiocyanates (1-5).Their anthelmintic and antimicrobial activities are reported.Of these 8 and 9 show 60-70percent reduction in worms at a dose of 100-250 mg/kg given for three days.
- Abuzar,Syed,Sharma, Satyavan
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p. 230 - 233
(2007/10/02)
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