- Selective Reduction of Nitroarenes to Arylamines by the Cooperative Action of Methylhydrazine and a Tris(N-heterocyclic thioamidate) Cobalt(III) Complex
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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.
- Ioannou, Dimitris I.,Gioftsidou, Dimitra K.,Tsina, Vasiliki E.,Kallitsakis, Michael G.,Hatzidimitriou, Antonios G.,Terzidis, Michael A.,Angaridis, Panagiotis A.,Lykakis, Ioannis N.
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p. 2895 - 2906
(2021/02/27)
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- Preparation of Well-Ordered Mesoporous-Silica-Supported Ruthenium Nanoparticles for Highly Selective Reduction of Functionalized Nitroarenes through Transfer Hydrogenation
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MCM-41-type mesoporous silica (OMS-IL) was prepared by using an ionic liquid (1-hexadecyl-3-methylimidazolium bromide) as a template. The XRD and TEM results demonstrated that OMS-IL was more stable than the MCM-41 material. Ru nanoparticles were supported on OMS-IL (Ru/OMS-IL) by impregnating OMS-IL with a RuCl3 aqueous solution, and the resulting material was used for the selective reduction of nitroarenes. The effects of the components of the catalysts and the reaction conditions on the catalytic behavior of the prepared catalysts were investigated in detail. Ru/OMS-IL exhibited high catalytic activity and chemoselectivity for the reduction of various substituted nitroarenes to the corresponding aromatic amines in ethanol with hydrazine hydrate as a hydrogen donor under mild conditions. The Ru/OMS-IL catalysts were highly stable and could easily be recovered by simple filtration over at least six recycling reactions without any observable loss in catalytic performance.
- Wei, Ning,Zou, Xiujing,Huang, Haigen,Wang, Xueguang,Ding, Weizhong,Lu, Xionggang
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supporting information
p. 209 - 214
(2018/01/26)
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- N,N'-bis-substituted aryl thiourea derivatives and synthetic method and application thereof
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The invention discloses N,N'-bis-substituted aryl thiourea derivatives which are a series of compounds simultaneously containing various substituted aromatic ring structures and asymmetric substituted thiourea structures and are all novel structural compounds which are not reported in the literature. The biological activity test analysis of all the target compounds includes determination of DPPH antioxidant activity and antiviral activity. Results indicate that, in general, the designed and synthesized compounds are novel in structures and have the antioxidant activity and the antiviral activity revealed for the first time. In addition, the unknown biological activity is not fully elucidated, and thus the compounds are expected to provide a certain material basis for further research and development of new drugs.
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Paragraph 0069-0071
(2017/04/26)
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- Discovery of a Series of 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-ones as Selective PI3K-δ/γ Inhibitors
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Dual inhibition of PI3K-δ and PI3K-γ is an established therapeutic strategy for treatment of hematological malignancies. Reported molecules targeting PI3K-δ/γ selectively are chemically similar and based upon isoquinolin-1(2H)-one or quinazolin-4(3H)-one scaffolds. Here we report a chemically distinct series of potent, selective PI3K-δ/γ inhibitors based on a 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one scaffold with comparable biochemical potency and cellular effects on PI3K signaling. We envisage these molecules will provide useful leads for development of next-generation PI3K-δ/γ targeting therapeutics.
- Ferguson, Fleur M.,Ni, Jing,Zhang, Tinghu,Tesar, Bethany,Sim, Taebo,Kim, Nam Doo,Deng, Xianming,Brown, Jennifer R.,Zhao, Jean J.,Gray, Nathanael S.
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supporting information
p. 908 - 912
(2016/10/22)
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- BENZOTHIAZOLE COMPOUNDS
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The present invention relates to benzothiazole compounds that mimic the activity of BH3 only proteins and are capable of binding to and neutralizing pro survival Bcl 2 proteins. The invention also relates to the use of such compounds in the regulation of cell death or cell survival and the treatment and/or prophylaxis of diseases or conditions associated with the deregulation of cell death or cell survival.
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Page/Page column 58-59
(2009/05/29)
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- 4, 6-DISUBSTITUTED AMINOPYRIMIDINE DERIVATIVES AS INHIBITORS OF PROTEIN KINASES
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The present invention relates to inhibitors of general Formula (I) of cyclin-dependent kinases and therapeutic applications thereof. Furthermore, the invention relates to compounds for preventing and/or treating any type of pain, inflammatory disorders, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases and neurodegenerative diseases.
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Page/Page column 156; 174
(2008/12/08)
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- SOLUBLE EPOXIDE HYDROLASE INHIBITORS
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Disclosed are sulfonamide compounds and compositions that inhibit soluble epoxide hydrolase (sEH), methods for preparing the compounds and compositions, and methods for treating patients with such compounds and compositions. The compounds, compositions, and methods are useful for treating a variety of sEH mediated diseases, including hypertensive, cardiovascular, inflammatory, pulmonary, and diabetes-related diseases.
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Page/Page column 52-53
(2008/06/13)
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- Isothiazoles as active-site inhibitors of HCV NS5B polymerase
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Isothiazole analogs were discovered as a novel class of active-site inhibitors of HCV NS5B polymerase. The best compound has an IC50 of 200 nM and EC50 of 100 nM, which is a significant improvement over the starting inhibitor (1). The X-ray complex structure of 1 with HCV NS5B was obtained at a resolution of 2.2 A, revealing that the inhibitor is covalently linked with Cys 366 of the 'primer-grip'. Furthermore, it makes considerable contacts with the C-terminus, β-loop, and more importantly, to the active-site of the enzyme. The uniqueness of this binding mode offers a new insight for the rational design of novel inhibitors for HCV NS5B polymerase.
- Yan, Shunqi,Appleby, Todd,Gunic, Esmir,Shim, Jae Hoon,Tasu, Tania,Kim, Hongwoo,Rong, Frank,Chen, Huaming,Hamatake, Robert,Wu, Jim Z.,Hong, Zhi,Yao, Nanhua
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- Acetamidine derivatives and their use as inhibitors for the nitric oxide synthase
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A class of acetamidine derivatives of general formula (I) STR1 wherein R1 is hydrogen, C1-6 hydrocarbyl group optionally substituted by halo, halo, nitro, cyano or a group XR3 wherein X is oxygen, C(O)m wherein m is 1 or 2, S(O)n wherein n is 0, 1 or 2, or a group NR4 wherein R4 is hydrogen or C1-6 alkyl; and R3 is hydrogen, C1-6 alkyl, or a group NR5 R6 wherein R5 and R6 are independently hydrogen or C1-6 alkyl, provided that R3 is not NR5 R6 when X is oxygen or S(O)n; R1a and R1b are independently selected from hydrogen and halo; R2 is a C1-14 hydrocarbyl group which may optionally contain one or two heteroatoms, the group R2 being optionally substituted by one or more groups independently selected from halo; N3 ; nitro; CF3 ; ZR7 wherein Z is oxygen, C(O)m' wherein m' is 1 or 2, S(O)n' wherein n' is 0, 1 or 2, or a group NR8 wherein R8 is hydrogen or C1-6 alkyl and R7 is hydrogen, C1-6 alkyl or a group NR9 R10 wherein R9 and R10 are independently hydrogen or C1-6 alkyl; or R2 is substituted by a group (a) STR2 wherein R11 has a definition the same as for R1 ; with the proviso that when R1 is a C1-6 alkyl group and R2 is a C1-14 hydrocarbyl substituted by two groups ZR7 wherein one group ZR7 is CO2 H, the other group ZR7 is not NH2; and salts thereof, methods for the manufacture thereof, and therapies, particularly inhibtion of nitric oxide synthase, is disclosed.
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- Carbonic anhydrase inhibitors - Part 49: Synthesis of substituted ureido and thioureido derivatives of aromatic/heterocyclic sulfonamides with increased affinities for isozyme I
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Reaction of nine aromatic/heterocyclic sulfonamides containing a free amino group with aryl isocyanates/isothiocyanates or allyl isothiocyanate afforded the corresponding urea/thiourea derivatives, which were characterized by standard physico-chemical procedures and assayed as inhibitors of three isozymes of carbonic anhydrase (CA), i.e. hCA I, hCA II and bCA IV (h = human, b = bovine isozyme). Another series of compounds, 1,5-disubstituted-2-thiobiuret derivatives, were prepared by reaction of 3,4-dichlorophenyl isocyanate with thioureido-containing aromatic/heterocyclic sulfonamides. Good inhibition of all these three CA isozymes was observed with the new compounds, but an exciting finding was that the ureas/thioureas and especially the above-mentioned thiobiurets reported here have an increased affinity to the slow isozyme hCA I, generally less susceptible to inhibition by sulfonamides, as compared to the rapid isozymes hCA II and bCA IV. Some of the new compounds might constitute good lead molecules for developing more selective CA I inhibitors.
- Supuran, Claudiu T.,Scozzafava, Andrea,Jurca, Bogdan C.,Ilies, Marc A.
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- N-phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: Structure-activity studies and demonstration of in vivo activity
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Selective inhibition of the neuronal isoform of nitric oxide synthase (NOS) compared to the endothelial and inducible isoforms may be required for treatment of neurological disorders caused by excessive production of nitric oxide. Recently, we described N-(3-(aminomethyl)benzyl)acetamidine (13) as a slow, tight-binding inhibitor, highly selective for human inducible nitric oxide synthase (iNOS). Removal of a single methylene bridge between the amidine nitrogen and phenyl ring to give N-(3- (aminomethyl)phenyl)acetamidine (14) dramatically altered the selectivity to give a neuronal selective nitric oxide synthase (nNOS) inhibitor. Part of this large shift in selectivity was due to 14 being a rapidly reversible inhibitor of iNOS in contrast to the essentially irreversible inhibition of iNOS observed with 13. Structure-activity studies revealed that a basic amine functionality tethered to an aromatic ring and a sterically compact amidine are key pharmacophores for this class of NOS inhibitors. Maximal nNOS inhibition potency was achieved with N-(3-(aminomethyl)phenyl)-2- furanylamidine (77) (K(i-nNOS) = 0.006 μM; K(i-eNOS) = 0.35 μM; K(i-iNOS) = 0.16 μM). Finally, α-fluoro-N-(3-(aminomethyl)phenyl)acetamidine (74) (K(i- nNOS) = 0.011 μM; K(i-eNOS) = 1.1 μM; K(i-iNOS) = 0.48 μM) had excellent brain penetration and inhibited nNOS in a rat brain slice assay as well as in the rat brain (cerebellum) in vivo. Thus, N-phenylamidines should be useful in validating the role of nNOS in neurological disorders.
- Collins, Jon L.,Shearer, Barry G.,Oplinger, Jeffrey A.,Lee, Shuliang,Garvey, Edward P.,Salter, Mark,Duffy, Claire,Burnette, Thimysta C.,Furfine, Eric S.
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p. 2858 - 2871
(2007/10/03)
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- Herbicidally active phenoxyalkanecarboxylic acid derivatives
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A compound of the formula: STR1 wherein Q1 is CH or N; R is H or C1 -C5 alkyl; X is H, halogen, CF3, or NO2 ; Y is H or halogen; Z is --O-- or --NH--; A is STR2 wherein Q2, and Q3 are each CH or N; R1 and R2 are each H, C1 -C5 alkyl, C1 -C5 alkoxy, or C2 -C6 alkxoycarobnyl; R3, R4, and R5 are each H or C1 -C5 alkyl; R6 is H, halogen, or C1 -C5 alkyl; R7, R8, R9, and R10 are each H or C1 -C5 alkyl; R11 is H, C1 -C5 alkyl, C1 -C5 alkoxy, C2 -C6 alkenyl, C6 -C10 aryl, C7 -C15 aryloxyalkyl, or C7 -C15 aralkyl; R12 and R13 are each H or C1 -C5 alkyl; R14 is C1 -C5 alkyl, C2 -C6 alkenyl, C5 -C10 aryl, or C7 -C15 aralkyl; or R13 and R14 taken together form C3 -C4 alkylene, V1 and V2 are each H, halogen, NO2, CN, or CF3 ; V3 is halogen or CF3 ; W1 is --O-- or --NH--; W2 is --(CH2)n -- wherein n is 0 or 1, or CO; X1 is halogen, or a salt thereof, which is effective as a herbicidal agent.
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