6967-12-0Relevant articles and documents
Selective Reduction of Nitroarenes to Arylamines by the Cooperative Action of Methylhydrazine and a Tris(N-heterocyclic thioamidate) Cobalt(III) Complex
Ioannou, Dimitris I.,Gioftsidou, Dimitra K.,Tsina, Vasiliki E.,Kallitsakis, Michael G.,Hatzidimitriou, Antonios G.,Terzidis, Michael A.,Angaridis, Panagiotis A.,Lykakis, Ioannis N.
, p. 2895 - 2906 (2021/02/27)
We report an efficient catalytic protocol that chemoselectively reduces nitroarenes to arylamines, by using methylhydrazine as a reducing agent in combination with the easily synthesized and robust catalyst tris(N-heterocyclic thioamidate) Co(III) complex [Co(κS,N-tfmp2S)3], tfmp2S = 4-(trifluoromethyl)-pyrimidine-2-thiolate. A series of arylamines and heterocyclic amines were formed in excellent yields and chemoselectivity. High conversion yields of nitroarenes into the corresponding amines were observed by using polar protic solvents, such as MeOH and iPrOH. Among several hydrogen donors that were examined, methylhydrazine demonstrated the best performance. Preliminary mechanistic investigations, supported by UV-vis and NMR spectroscopy, cyclic voltammetry, and high-resolution mass spectrometry, suggest a cooperative action of methylhydrazine and [Co(κS,N-tfmp2S)3] via a coordination activation pathway that leads to the formation of a reduced cobalt species, responsible for the catalytic transformation. In general, the corresponding N-arylhydroxylamines were identified as the sole intermediates. Nevertheless, the corresponding nitrosoarenes can also be formed as intermediates, which, however, are rapidly transformed into the desired arylamines in the presence of methylhydrazine through a noncatalytic path. On the basis of the observed high chemoselectivity and yields, and the fast and clean reaction processes, the present catalytic system [Co(κS,N-tfmp2S)3]/MeNHNH2 shows promise for the efficient synthesis of aromatic amines that could find various industrial applications.
Discovery of 1-(1H-indazol-4-yl)-3-((1-phenyl-1H-pyrazol-5-yl)methyl) ureas as potent and thermoneutral TRPV1 antagonists
Kang, Jin Mi,Kwon, Sun Ok,Ann, Jihyae,Blumberg, Peter M.,Ha, Heejin,Yoo, Young Dong,Frank-Foltyn, Robert,Lesch, Bernhard,Bahrenberg, Gregor,Stockhausen, Hannelore,Christoph, Thomas,Lee, Jeewoo
, (2020/10/06)
A series of 1-indazol-3-(1-phenylpyrazol-5-yl)methyl ureas were investigated as hTRPV1 antagonists. The structure–activity relationship study was conducted systematically for both the indazole A-region and the 3-trifluoromethyl/t-butyl pyrazole C-region to optimize the antagonism toward the activation by capsaicin. Among them, the antagonists 26, 50 and 51 displayed highly potent antagonism with Ki(CAP) = 0.4–0.5 nM. Further, in vivo studies in mice indicated that these derivatives both antagonized capsaicin induced hypothermia, consistent with their in vitro activity, and themselves did not induce hyperthermia. In the formalin model, 51 showed anti-nociceptive activity in a dose-dependent manner.
Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents
Anh, Le Viet,Hai, Dinh Thi Thanh,Han, Byung Woo,Hien, Tran Thi Thu,Hoang, Ngo Xuan,Hoang, Van-Hai,Long, Nguyen Huu,Luu, Hung N.,Luu, Thi-Thu-Trang,Ngo, Son Tung,Ngo, Thien,Nguyen, Thanh Xuan,Nguyen, Yen Thi Kim,Tran, Phuong-Thao,Van Hieu, Duong
, p. 45199 - 45206 (2020/12/30)
In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currently on clinical trials, and the important anticancer activity of the indazole scaffold. One of them, compound N-(4-fluorobenzyl)-1,3-dimethyl-1H-indazol-6-amine (36), exhibited a potent anti-proliferative activity with an IC50 value of 0.4 ± 0.3 μM in human colorectal cancer cells (HCT116). This compound also remarkably suppressed the IDO1 protein expression. In the cell-cycle studies, the suppressive activity of compound 36 in HCT116 cells was related to the G2/M cell cycle arrest. Altogether, the current findings demonstrate that compound 36 would be promising for further development as a potential anticancer agent.
Wnt signal pathway inhibitor and use thereof
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Paragraph 0047; 0184-0187, (2017/08/10)
The invention relates to heterocyclic compounds with Wnt signal channel inhibition activity, particularly including compounds, pharmaceutically acceptable salts, various isotopes, various isomers or various crystal structures thereof having a structure represented by a general formula I (shown in the specification). By the compounds and a composition of the compounds, a Wnt signal channel can be effectively inhibited and diseases related to the Wnt signal channel can be treated or prevented.
An efficient in-situ reduction and cyclization reaction for the synthesis of 9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one, 11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo [3,4-a]acridin-10-one, and 11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives
Yan, Lirong,Li, Qingyang,Xu, Hui,Xu, Zhongyun,Yu, Qiuyu,Qin, Yaqi,Rong, Liangce
, p. 6805 - 6814 (2017/11/09)
An efficient in-situ reduction and cyclization reaction was reported from the aromatic aldehydes, 6-nitro-1H-indazole (5-nitrobenzimidazole), and 2,2-dimethyl-1,3-dioxane-4,6-dione (1,3-cyclohexanedione or dimedone) to synthesize 9-aryl-1,6,8,9-tetrahydro-7H-pyrazolo[3,4-f]quinolin-7-one, 11-aryl-1,6,7,8,9,11-hexahydro-10H-pyrazolo [3,4-a]acridin-10-one, and 11-aryl-3,6,7,8,9,11-hexahydro-10H-imidazo[4,5-a]acridin-10-one derivatives in the presence of SnCl2·2H2O in THF medium. The advantages of this method are mild conditions, convenient manipulation, high yields and wide range of substrates.
HEPARAN SULFATE BIOSYNTHESIS INHIBITORS FOR THE TREATMENT OF DISEASES
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Paragraph 000327, (2016/05/02)
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions in need of inhibition of heparan sulfate biosynthesis.
Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors
Dong, Yan,Li, Kehuang,Xu, Zhixiang,Ma, Haikuo,Zheng, Jiyue,Hu, Zhilin,He, Sudan,Wu, Yiyuan,Sun, Zhijian,Luo, Lusong,Li, Jiajun,Zhang, Hongjian,Zhang, Xiaohu
, p. 6855 - 6868 (2015/11/11)
The Wnt signaling pathway is a pivotal developmental pathway. It operates through control of cellular functions such as proliferation, differentiation, migration and polarity. Aberrant Wnt signaling has been implicated in the formation and metastasis of tumors. Porcupine is a component of the Wnt signaling pathway. It is a member of the membrane-bound O-acyltransferase family of proteins. Porcupine catalyzes the palmitoylation of Wnt proteins, a process which is essential to their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from two known porcupine inhibitor classes. The leading compound 62 demonstrated subnanomolar (IC50 0.11 nM) inhibition of Wnt signaling in a paracrine cellular reporter gene assay. Compound 62 also potently inhibited Wnt secretion into culture medium, an indication of direct inhibition of the porcupine protein. Furthermore, compound 62 showed excellent chemical, plasma and liver microsomal stabilities. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors.
Mild and selective hydrogenation of nitro compounds using palladium nanoparticles supported on amino-functionalized mesocellular foam
Verho, Oscar,Gustafson, Karl P. J.,Nagendiran, Anuja,Tai, Cheuk-Wai,B?ckvall, Jan-E.
, p. 3153 - 3159 (2015/02/03)
We present the utilization of a heterogeneous catalyst comprised of Pd nanoparticles supported on aminopropyl-functionalized siliceous mesocellular foam (Pd0-AmP-MCF) for the selective hydrogenation of aromatic, aliphatic, and heterocyclic nitro compounds to the corresponding amines. In general, the catalytic protocol exclusively affords the desired amine products in excellent yields within short reaction times with the reactions performed at room temperature under ambient pressure of H2. Moreover, the reported Pd nanocatalyst displayed excellent structural integrity for this transformation as it could be recycled multiple times without any observable loss of activity or leaching of metal. In addition, the Pd nanocatalyst could be easily integrated into a continuous-flow device and used for the hydrogenation of 4-nitroanisole on a 2.5 g scale, where the product p-anisidine was obtained in 95% yield within 2 h with a Pd content of less than 1 ppm.
Polymethylhydrosiloxane derived palladium nanoparticles for chemo- and regioselective hydrogenation of aliphatic and aromatic nitro compounds in water
Damodara, Dandu,Arundhathi, Racha,Ramesh Babu, T. Venkata,Legan, Margaret K.,Kumpaty, Hephzibah J.,Likhar, Pravin R.
, p. 22567 - 22574 (2014/06/23)
Chemo- and regioselective hydrogenation of a wide range of aliphatic, unsaturated, aromatic and heteroaromatic nitro compounds into their corresponding amines has been achieved with highly efficient polysiloxane-stabilised "Pd" nanoparticles on NAP-magnesium oxide supports using an environmentally friendly hydrogenating agent, polymethylhydrosiloxane [PMHS] in water. Highly stable and active Pd nanoparticles were prepared by the reduction of NAP-Mg-PdCl4 with PMHS, which serves as a reducing agent as well as a capping agent. The well-dispersed palladium nanoparticles on NAP-MgO catalysts also exhibit excellent regioselectivity in the hydrogenation of dinitrobenzenes to the corresponding nitroanilines. The catalyst has high durability against sintering during the hydrogenation reaction and can be reused with no loss in its activity. This journal is the Partner Organisations 2014.
Mechanistic studies of the reduction of nitroarenes by NaBH4 or hydrosilanes catalyzed by supported gold nanoparticles
Fountoulaki, Stella,Daikopoulou, Vassiliki,Gkizis, Petros L.,Tamiolakis, Ioannis,Armatas, Gerasimos S.,Lykakis, Ioannis N.
, p. 3504 - 3511 (2015/02/19)
Herein, we show that mesoporous titania-supported gold nanoparticle assemblies (Au/MTA) catalyze the activation of NaBH4 and 1,1,3,3-tetramethyl disiloxane (TMDS) compounds, which act as transfer hydrogenation agents for the reduction of nitroarenes to the corresponding anilines in moderate to high yields. On the other hand, nitroalkanes are reduced to the corresponding diazo and hydrazo compounds under the studied conditions. The substantial measured primary kinetic isotope effects found here suggested that B-H bond cleavage occurs in a rate-determining step and [Au]-H active hybrids are formed, which are responsible for the reduction of nitroarenes to the corresponding amines. Formal Hammett-type kinetic analysis of a range of para-X-substituted nitroarenes lends support to this hypothesis. Nitro compounds substituted with electron-withdrawing groups were reduced faster than the corresponding compounds with electron-donating groups. The presence of water enhanced the catalytic activity of Au/MTA in aprotic solvents. Nuclear magnetic resonance studies support the formation of the corresponding hydroxylamines as the only intermediate products. On the basis of the high observed chemoselectivities and the fast and clean reaction processes, these catalytic systems, i.e., Au/MTA-NaBH4 and Au/MTA-TMDS, show promise for the efficient synthesis of aromatic amines at industrial levels.
