- Inhibitors of ribosome rescue arrest growth of francisella tularensis at all stages of intracellular replication
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Bacteria require at least one pathway to rescue ribosomes stalled at the ends of mRNAs. The primary pathway for ribosome rescue is trans-translation, which is conserved in >99% of sequenced bacterial genomes. Some species also have backup systems, such as ArfA or ArfB, which can rescue ribosomes in the absence of sufficient trans-translation activity. Small-molecule inhibitors of ribosome rescue have broad-spectrum antimicrobial activity against bacteria grown in liquid culture. These compounds were tested against the tier 1 select agent Francisella tularensis to determine if they can limit bacterial proliferation during infection of eukaryotic cells. The inhibitors KKL-10 and KKL-40 exhibited exceptional antimicrobial activity against both attenuated and fully virulent strains of F. tularensis in vitro and during ex vivo infection. Addition of KKL-10 or KKL-40 to macrophages or liver cells at any time after infection by F. tularensis prevented further bacterial proliferation. When macrophages were stimulated with the proinflammatory cytokine gamma interferon before being infected by F. tularensis, addition of KKL-10 or KKL-40 reduced intracellular bacteria by >99%, indicating that the combination of cytokine-induced stress and a nonfunctional ribosome rescue pathway is fatal to F. tularensis. Neither KKL-10 nor KKL-40 was cytotoxic to eukaryotic cells in culture. These results demonstrate that ribosome rescue is required for F. tularensis growth at all stages of its infection cycle and suggest that KKL-10 and KKL-40 are good lead compounds for antibiotic development.
- Goralski, Tyler D. P.,Dewan, Kalyan K.,Alumasa, John N.,Avanzato, Victoria,Place, David E.,Markley, Rachel L.,Katkere, Bhuvana,Rabadi, Seham M.,Bakshi, Chandra Shekhar,Keiler, Kenneth C.,Kirimanjeswara, Girish S.
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- Prazosin-Related Compounds. Effect of Transforming the Piperazinylquinazoline Moiety into an Aminomethyltetrahydroacridine System on the Affinity for α1-Adrenoreceptors
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In a search for structurally new α1-adrenoreceptor (α1-AR) antagonists, prazosin (1)-related compounds 2-11 were synthesized and their affinity profiles were assessed by functional experiments in isolated rat vas deferens (α1A), spleen (β 1B), and aorta (α1D) and by binding assays in CHO cells expressing human cloned α1-AR subtypes. Transformation of the piperazinylquinazoline moiety of 1 into an aminomethyltetrahydroacridine system afforded compound 2, endowed with reduced affinity, in particular for the α1A-AR subtype. Then, to investigate the optimal features of the tricyclic moiety, the aliphatic ring of 2 was modified by synthesizing the lower and higher homologues 3 and 4. An analysis of the pharmacological profile, together with a molecular modeling study, indicated the tetrahydroacridine moiety as the most promising skeleton for α 1-antagonism. Compounds 5-8, where the replacement of the furoyl group of 2 with a benzoyl moiety afforded the possibility to evaluate the effect of the substituent trifluoromethyl on receptor binding, resulted, except for 7, in a rather surprising selectivity toward α1B-AR, in particular vs the α1A subtype. Also the insertion of the 2,6-dimethoxyphenoxyethyl function of WB 4101 on the tetrahydroacridine skeleton of 2, and/or the replacement of the aromatic amino function with a hydroxy group, affording derivatives 9-11, resulted in α1B-AR selectivity also vs the α1D subtype. On the basis of these results, the tetrahydroacridine moiety emerged as a promising tool for the characterization of the α1-AR, owing to the receptor subtype selectivity achieved by an appropriate modification of the lateral substituents.
- Rosini, Michela,Antonello, Alessandra,Cavalli, Andrea,Bolognesi, Maria L.,Minarini, Anna,Marucci, Gabriella,Poggesi, Elena,Leonardi, Amedeo,Melchiorre, Carlo
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- Remarkably Efficient Iridium Catalysts for Directed C(sp2)-H and C(sp3)-H Borylation of Diverse Classes of Substrates
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Here we describe the discovery of a new class of C-H borylation catalysts and their use for regioselective C-H borylation of aromatic, heteroaromatic, and aliphatic systems. The new catalysts have Ir-C(thienyl) or Ir-C(furyl) anionic ligands instead of the diamine-type neutral chelating ligands used in the standard C-H borylation conditions. It is reported that the employment of these newly discovered catalysts show excellent reactivity and ortho-selectivity for diverse classes of aromatic substrates with high isolated yields. Moreover, the catalysts proved to be efficient for a wide number of aliphatic substrates for selective C(sp3)-H bond borylations. Heterocyclic molecules are selectively borylated using the inherently elevated reactivity of the C-H bonds. A number of late-stage C-H functionalization have been described using the same catalysts. Furthermore, we show that one of the catalysts could be used even in open air for the C(sp2)-H and C(sp3)-H borylations enabling the method more general. Preliminary mechanistic studies suggest that the active catalytic intermediate is the Ir(bis)boryl complex, and the attached ligand acts as bidentate ligand. Collectively, this study underlines the discovery of new class of C-H borylation catalysts that should find wide application in the context of C-H functionalization chemistry.
- Chattopadhyay, Buddhadeb,Hassan, Mirja Md Mahamudul,Hoque, Md Emdadul
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supporting information
p. 5022 - 5037
(2021/05/04)
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- Rhodium(III)-catalyzed chemodivergent annulations between phenyloxazoles and diazos via C–H activation
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Acid-controlled, chemodivergent and redox-neutral annulations for the synthesis of isocoumarins and isoquinolinones have been realized via Rh(III)-catalyzed C[sbnd]H activation. Diazo compounds act as a carbene precursor, and coupling occurs in one-pot process, where adipic acid and trimethylacetic acid promote chemodivergent cyclizations.
- Zhang, Xueguo,Wang, Peigen,Zhu, Liangwei,Chen, Baohua
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supporting information
p. 695 - 699
(2020/06/28)
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- Ni-Catalyzed C(sp2)-H alkylation ofN-quinolylbenzamides using alkylsilyl peroxides as structurally diverse alkyl sources
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A Ni-catalyzed direct C-H alkylation ofN-quinolylbenzamides using alkylsilyl peroxides as alkyl-radical precursors is described. The reaction forms a new C(sp3)-C(sp2) bondviathe selective cleavage of both C(sp3)-C(sp3) and C(sp2)-H bonds. This transformation shows a high functional-group tolerance and, due to the structural diversity of alkylsilyl peroxides, a wide range of alkyl chains including functional groups and complex structures can be introduced at theortho-position of readily availableN-quinolylbenzamide derivatives. Mechanistic studies suggest that the reaction involves a radical mechanism.
- Kano, Taichi,Maruoka, Keiji,Matsumoto, Akira,Sakurai, Shunya,Tsuzuki, Saori
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supporting information
p. 7942 - 7945
(2021/08/17)
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- Synthesis and structure-activity relationship studies of n-monosubstituted aroylthioureas as urease inhibitors
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Background: Thiourea is a classical urease inhibitor which is usually used as a positive control, and many N,N'-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N'-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thiourea with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated via surface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11, and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in the intact cell, with IC50 values being 90-to 450-fold and 5-to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed an IC50 value of 0.060 ± 0.004μM against cell-free urease, which bound to urea binding site with a very low KD value (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11 was also demonstrated to have very low cytotoxicity to mammalian cells. Conclusion: The results revealed that N-monosubstituted aroylthioureas bound to the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by urease-containing pathogens.
- Dawalamu,Fang, Hai-Lian,Fu, Zi-Juan,Li, Fang,Li, Ke,Li, Wei-Yi,Liu, Li,Ni, Wei-Wei,Ouyang, Hui,Xiao, Zhu-Ping,Ye, Ya-Xi,Zhu, Hai-Liang,Zhu, Wen-Yan,Zou, Xia
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p. 1046 - 1059
(2021/11/30)
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- Copper-mediated C–H thiolation of (hetero)arenes using weakly coordinating directing group
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We have developed a copper-mediated C–H thiolation of (hetero)arenes by using monodentate amide as weakly coordinating directing group. This protocol features excellent functional group tolerance and shows satisfactory compatibility with various heterocycles, such as indole, pyrrole, imidazole, pyridine, thiophene and quinoline. The robust nature of this protocol renders that it has potential value in the synthetic application.
- Wu, Peng,Cheng, Tai-Jin,Lin, Hai-Xia,Xu, Hui,Dai, Hui-Xiong
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supporting information
(2020/06/17)
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- Base-promoted Lewis acid catalyzed synthesis of quinazoline derivatives
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A one-pot protocol has been developed for the synthesis of quinazolinones from amide-oxazolines with TsCl via a cyclic 1,3-azaoxonium intermediate and 6π electron cyclization in the presence of a Lewis acid and base. The process is operationally simple and has a broad substrate scope. This method provides a unique strategy for the construction of quinazolinones.
- Cui, Xin-Feng,Hu, Fang-Peng,Huang, Guo-Sheng,Lu, Guo-Qiang
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supporting information
p. 4376 - 4380
(2020/10/20)
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- Divergent Synthesis of Tunable Cyclopentadienyl Ligands and Their Application in Rh-Catalyzed Enantioselective Synthesis of Isoindolinone
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A series of rhodium complexes bearing sterically and electronically tunable cyclopentadienyl ligands, prepared by utilizing Co2(CO)8-mediated [2+2+1] cyclization as a key step, were synthesized. In the presence of 2.5 mol% of CpmRh4, unprecedented enantioselective [4+1] annulation reaction of benzamides and alkenes was achieved with a broad substrate scope under mild reaction conditions, providing a variety of isoindolinones with excellent regio-and enantioselectivity (up to 94% yield, 97:3 er). Preliminary mechanistic studies suggest that the reaction involves an oxidative Heck reaction and an intramolecular enantioselective alkene hydroamination reaction.
- Cui, Wen-Jun,Wu, Zhi-Jie,Gu, Qing,You, Shu-Li
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supporting information
p. 7379 - 7385
(2020/08/19)
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- Synthesis of quinazolin-4(1 H)-ones via amination and annulation of amidines and benzamides
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Quinazolinones have broad applications in the biological, pharmaceutical and material fields. Studies on the synthesis of these compounds are therefore widely conducted. Herein, a novel and highly efficient copper-mediated tandem C(sp2)-H amination and annulation of benzamides and amidines for the synthesis of quinazolin-4(1H)-ones is proposed. This synthetic route can be useful for the construction of quinazolin-4(1H)-one frameworks.
- Hu, Fangpeng,Cui, Xinfeng,Ban, Zihui,Lu, Guoqiang,Luo, Nan,Huang, Guosheng
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supporting information
p. 2356 - 2360
(2019/03/06)
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- Electrooxidative amination of sp2 C-H bonds: Coupling of amines with aryl amides via copper catalysis
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Metal-catalyzed cross-coupling reactions are among the most important transformations in organic synthesis. However, the use of C-H activation for sp2 C-N bond formation remains one of the major challenges in the field of cross-coupling chemistry. Described herein is the first example of the synergistic combination of copper catalysis and electrocatalysis for aryl C-H amination under mild reaction conditions in an atom-and step-economical manner with the liberation of H2 as the sole and benign byproduct.
- Kathiravan, Subban,Suriyanarayanan, Subramanian,Nicholls, Ian A.
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supporting information
p. 1968 - 1972
(2019/03/07)
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- Palladium-Catalyzed Electrochemical C-H Bromination Using NH4Br as the Brominating Reagent
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The palladium-catalyzed electrochemical C-H bromination of benzamide derivatives under divided cells is developed, in which NH4Br serves as a brominating reagent and electrolyte. The protocol avoids the use of chemical oxidants and provides an alternative method for the synthesis of aryl bromides.
- Yang, Qi-Liang,Wang, Xiang-Yang,Wang, Tong-Lin,Yang, Xiang,Liu, Dong,Tong, Xiaofeng,Wu, Xin-Yan,Mei, Tian-Sheng
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supporting information
p. 2645 - 2649
(2019/04/17)
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- Ligand-Promoted RhIII-Catalyzed Thiolation of Benzamides with a Broad Disulfide Scope
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A ligand-promoted RhIII-catalyzed C(sp2)?H activation/thiolation of benzamides has been developed. Using bidentate mono-N-protected amino acid ligands led to the first example of RhIII-catalyzed aryl thiolation reactions directed by weakly coordinating directing amide groups. The reaction tolerates a broad range of amides and disulfide reagents.
- Kang, Yan-Shang,Zhang, Ping,Li, Min-Yan,Chen, You-Ke,Xu, Hua-Jin,Zhao, Jing,Sun, Wei-Yin,Yu, Jin-Quan,Lu, Yi
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supporting information
p. 9099 - 9103
(2019/06/13)
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- Synthesis, antimicrobial, antioxidant, cytotoxic, antiurease and molecular docking studies of N-(3-trifluoromethyl)benzoyl-N′-aryl thiourea derivatives
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An irrefutable advancement has been noted for the infectious diseases caused due to ureolytic bacteria through the development of various drugs. Keeping in mind the extremely valuable synthetic utility and medicinal significance of thiourea derivatives, synthesis of new 3-trifluoromethyl benzoic acid thiourea derivatives (3a–j) were carried out. The biological potential of all compounds in terms of antimicrobial, antioxidant, cytotoxic and antiurease activities were studied. The compounds 3a, 3c and 3i with dichloro and methoxy groups substitution on the aryl group showed significant activity against all strain of bacteria while moderate to no activity was observed in remaining compounds. Whereas the antifungal evaluation showed that all compounds were active againts C. Albican and no activity was observed against C. Prapsilosis. The cytotoxic findings revealed the non-toxic nature of these compounds as IC50 values of majority of the compounds are above 100 μm except for compounds 3f and 3g. In addition, these compounds exhibited better antioxidant potential as 100 μm concentration inhibited >50% reactive oxygen species (ROS) production except compounds 3e, 3f and 3j. The compound 3a proved to be the most potent urease inhibitor showing the highest enzyme % inhibition (93.1%) with IC50 value of 8.17 ± 0.24 μM and found more active as compare to standard followed by compound 3e (92.6%), 3h (91.6%), 3d (90.8%), 3b (90.6%) and 3f (90.0%) with their respective IC50 values. All the synthesized compounds were docked into the binding cavity of Urease (PDB ID: 4ubp). The most active compound 3a was also ranked as top on the docking score as it was found to show valuable interactions with the target protein along with good docking scores. Hence our results revealed that the synthesized compounds have potential to be used as potent urease inhibitors after further detailed mechanistic studies.
- Maalik, Aneela,Rahim, Hina,Saleem, Muhammad,Fatima, Nighat,Rauf, Abdur,Wadood, Abdul,Malik, Muhammad Imran,Ahmed, Ayaz,Rafique, Hummera,Zafar, Muhammad Naveed,Riaz, Muhammad,Rasheed, Lubna,Mumtaz, Amara
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- Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model
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Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50 = 3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole)were evaluated in comparison to MY 5445 (4b)in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment.
- Bollenbach, Maud,Lugnier, Claire,Kremer, Mélanie,Salvat, Eric,Megat, Salim,Bihel, Frédéric,Bourguignon, Jean-Jacques,Barrot, Michel,Schmitt, Martine
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supporting information
p. 269 - 290
(2019/06/05)
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- Cu-Mediated C-H Thioetherification of Arenes at Room Temperature
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Cu-mediated C-H thioetherification of arenes with ethylene sulfide has been developed using a readily removable directing group. The reaction proceeded at room temperature, and a variety of sensitive functional groups including chloro, bromo, and vinyl were well tolerated. The thiolated products could be converted to the seven-membered benzoxathiepinones derivatives by a sequence of hydrolysis-lactonization reactions.
- Wang, Xing,Yi, Xing,Xu, Hui,Dai, Hui-Xiong
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supporting information
p. 5981 - 5985
(2019/08/26)
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- Discovery of Inhibitors of Aurora/PLK Targets as Anticancer Agents
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Aurora and polo-like kinases control the G2/M phase in cell mitosis, which are both considered as crucial targets for cancer cell proliferations. Here, naphthalene-based Aurora/PLK coinhibitors as leading compounds were designed through in silico approach, and a total of 36 derivatives were synthesized. One candidate (AAPK-25) was selected under in vitro cell based high throughput screening with an IC50 value = 0.4 μM to human colon cancer cell HCT-116. A kinome scan assay showed that AAPK-25 was remarkably selective to both Aurora and PLK families. The relevant genome pathways were also depicted by microarray based gene expression analysis. Furthermore, validated from a set of in vitro and in vivo studies, AAPK-25 significantly inhibited the development of the colon cancer growth and prolonged the median survival time at the end of the administration (p 0.05). To sum up, AAPK-25 has a great potential to be developed for a chemotherapeutic agent in clinical use.
- Qi, Baowen,Zhong, Ling,He, Jun,Zhang, Hongjia,Li, Fengqiong,Wang, Ting,Zou, Jing,Lin, Yao-Xin,Zhang, Chengchen,Guo, Xiaoqiang,Li, Rui,Shi, Jianyou
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supporting information
p. 7697 - 7707
(2019/09/10)
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- Optimization of a 1,3,4-oxadiazole series for inhibition of Ca2+/calmodulin-stimulated activity of adenylyl cyclases 1 and 8 for the treatment of chronic pain
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Adenylyl cyclases type 1 (AC1) and 8 (AC8) are group 1 transmembrane adenylyl cyclases (AC) that are stimulated by Ca2+/calmodulin. Studies have shown that mice depleted of AC1 have attenuated inflammatory pain response, while AC1/AC8 double-knockout mice display both attenuated pain response and opioid dependence. Thus, AC1 has emerged as a promising new target for treating chronic pain and opioid abuse. We discovered that the 1,3,4-oxadiazole scaffold inhibits Ca2+/calmodulin-stimulated cyclic adenosine 3‘,5‘-monophosphate (cAMP) production in cells stably expressing either AC1 or AC8. We then carried out structure-activity relationship studies, in which we designed and synthesized 65 analogs, to modulate potency and selectivity versus each AC isoform in cells. Furthermore, molecular docking of the analogs into an AC1 homology model suggests the molecules may bind at the ATP binding site. Finally, a prioritized analog was tested in a mouse model of inflammatory pain and exhibited modest analgesic properties. In summary, our data indicate the 1,3,4-oxadiazoles represent a novel scaffold for the cellular inhibition of Ca2+/calmodulin-stimulated AC1- and AC8 cAMP and warrant further exploration as potential lead compounds for the treatment of chronic inflammatory pain.
- Kaur, Jatinder,Soto-Velasquez, Monica,Ding, Zhong,Ghanbarpour, Ahmadreza,Lill, Markus A.,van Rijn, Richard M.,Watts, Val J.,Flaherty, Daniel P.
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p. 568 - 585
(2018/11/26)
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- CoIII-Catalyzed Isonitrile Insertion/Acyl Group Migration Between C?H and N?H bonds of Arylamides
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A general efficient and site-selective cobalt-catalyzed insertion of isonitrile into C?H and N?H bonds of arylamides through C?H bond activation and alcohol assisted intramolecular trans-amidation is demonstrated. This straightforward approach overcomes the limitation by the presence of strongly chelating groups. Isolation of CoIII-isonitrile complex B has been achieved for the first time to understand the reaction mechanism.
- Kalsi, Deepti,Barsu, Nagaraju,Sundararaju, Basker
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supporting information
p. 2360 - 2364
(2018/02/22)
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- Pharmaceutical-Oriented Methoxylation of Aryl C(sp 2)-H Bonds using Copper Catalysts
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A pharmaceutical-oriented, copper(II)-catalyzed methoxylation of aryl C(sp 2)-H bonds has been developed. This simple and environmentally benign reaction system occurs efficiently using oxygen as oxidant with broad substrate scope and high functional group tolerance.
- Zhang, Guofu,Zhu, Jianfei,Tong, Chaolai,Ding, Chengrong
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supporting information
p. 1451 - 1454
(2018/05/14)
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- Hemozoin inhibiting 2-phenylbenzimidazoles active against malaria parasites
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The 2-phenylbenzimidazole scaffold has recently been discovered to inhibit β-hematin (synthetic hemozoin) formation by high throughput screening. Here, a library of 325,728 N-4-(1H-benzo[d]imidazol-2-yl)aryl)benzamides was enumerated, and Bayesian statistics used to predict β-hematin and Plasmodium falciparum growth inhibition. Filtering predicted inactives and compounds with negligible aqueous solubility reduced the library to 35,124. Further narrowing to compounds with terminal aryl ring substituents only, reduced the library to 18, 83% of which were found to inhibit β-hematin formation 100 μM and 50% parasite growth 2 μM. Four compounds showed nanomolar parasite growth inhibition activities, no cross-resistance in a chloroquine resistant strain and low cytotoxicity. QSAR analysis showed a strong association of parasite growth inhibition with inhibition of β-hematin formation and the most active compound inhibited hemozoin formation in P. falciparum, with consequent increasing exchangeable heme. Pioneering use of molecular docking for this system demonstrated predictive ability and could rationalize observed structure activity trends.
- L'abbate, Fabrizio P.,Müller, Ronel,Openshaw, Roxanne,Combrinck, Jill M.,de Villiers, Katherine A.,Hunter, Roger,Egan, Timothy J.
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p. 243 - 254
(2018/10/15)
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- Copper-Mediated Cyanation of Aryl C—H Bond with Removable Bidenate Auxiliary Using Acetonitrile as the Cyano Source
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Copper-mediated cyanation of aryl C—H bond with removable bidenate auxiliary as a directing group has been developed, in which green and cheap acetonitrile is used as the “CN” source. By switching the reaction conditions, the C—H cyanated products and N-Ar-phthalimides can be provided in acceptable yields with high chemoselectivity, respectively. The use of quaternary ammonium salt is essential for cyanation reaction.
- Yu, Zhengwei,Zhang, Saisai,Shen, Zengming
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supporting information
p. 1139 - 1142
(2018/10/15)
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- Metathesis-active ligands enable a catalytic functional group metathesis between aroyl chlorides and aryl iodides
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Current methods for functional group interconversion have, for the most part, relied on relatively strong driving forces which often require highly reactive reagents to generate irreversibly a desired product in high yield and selectivity. These approaches generally prevent the use of the same catalytic strategy to perform the reverse reaction. Here we describe a catalytic functional group metathesis approach to interconvert, under CO-free conditions, two synthetically important classes of electrophiles that are often employed in the preparation of pharmaceuticals and agrochemicals—aroyl chlorides (ArCOCl) and aryl iodides (ArI). Our reaction design relies on the implementation of a key reversible ligand C–P bond cleavage event, which enables a non-innocent, metathesis-active phosphine ligand to mediate a rapid aryl group transfer between the two different electrophiles. Beyond enabling a practical and safer approach to the interconversion of ArCOCl and ArI, this type of ligand non-innocence provides a blueprint for the development of a broad range of functional group metathesis reactions employing synthetically relevant aryl electrophiles.
- Lee, Yong Ho,Morandi, Bill
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p. 1016 - 1022
(2018/09/06)
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- Ortho lithiation-in situ borylation of substituted morpholine benzamides
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Morpholine amides are cheap and safe alternative to Weinreb amides as acylating agents of organometallic species. Herein, the in-situ lithiation/borylation of 18 ortho- meta- and para-substituted morpholine benzamides has been investigated. 10 of the 18 substrates provided the desired boronic esters as the major isomer (>90% regioselectivity) in crude isolated yields ranging from 68 to 93%. The synthetic usability of such building blocks was subsequently illustrated via the synthesis of a kinase inhibitor.
- Cederbalk, Anna,Lysén, Morten,Kehler, Jan,Kristensen, Jesper L.
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p. 1576 - 1582
(2017/03/08)
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- Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a highly selective irreversible Bruton's tyrosine kinase (BTK) inhibitor
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Currently there are several irreversible BTK inhibitors targeting Cys481 residue under preclinical or clinical development. However, most of these inhibitors also targeted other kinases such as BMX, JAK3, and EGFR that bear the highly similar active cysteine residues. Through a structure-based drug design approach, we discovered a highly potent (IC50: 7?nM) irreversible BTK inhibitor compound 9 (CHMFL-BTK-01), which displayed a high selectivity profile in KINOMEscan (S score (35)?=?0.00) among 468 kinases/mutants at the concentration of 1?μM. Compound 9 completely abolished BMX, JAK3 and EGFR's activity. Both X-ray crystal structure and cysteine-serine mutation mediated rescue experiment confirmed 9's irreversible binding mode. 9 also potently inhibited BTK Y223 auto-phosphorylation (EC50: 30?nM), arrested cell cycle in G0/G1 phase and induced apoptosis in U2932 and Pfeiffer cells. We believe these features would make 9 a good pharmacological tool to study the BTK related pathology.
- Liang, Qianmao,Chen, Yongfei,Yu, Kailin,Chen, Cheng,Zhang, Shouxiang,Wang, Aoli,Wang, Wei,Wu, Hong,Liu, Xiaochuan,Wang, Beilei,Wang, Li,Hu, Zhenquan,Wang, Wenchao,Ren, Tao,Zhang, Shanchun,Liu, Qingsong,Yun, Cai-Hong,Liu, Jing
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p. 107 - 125
(2017/03/21)
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- Cp?CoIII-Catalyzed syn-Selective C-H Hydroarylation of Alkynes Using Benzamides: An Approach Toward Highly Conjugated Organic Frameworks
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Hydroarylation of internal alkynes by cost-effective CoIII-catalysis, directed by N-tert-butyl amides, is achieved to avail mono- or dihydroarylated amide products selectively in an atom and step economic way. Several important functional groups were tolerated under the reaction conditions, and syn-hydroarylation products were exclusively isolated. Notably, a 4-fold C-H hydroarylation provided a highly conjugated organic framework in one step. Kinetic study with extensive deuterium labeling experiments were performed to support the proposed mechanism.
- Bera, Sourav Sekhar,Debbarma, Suvankar,Ghosh, Avick Kumar,Chand, Santanu,Maji, Modhu Sudan
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p. 420 - 430
(2017/04/26)
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- Design, synthesis and evaluation of azaacridine derivatives as dual-target EGFR and Src kinase inhibitors for antitumor treatment
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Overexpression of EGFR is often associated with advanced stage disease and poor prognosis. In certain cancers, Src works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and Src is of therapeutic advantage against these cancers. Based on molecular docking and our previous studies, we rationally designed a new series of azaacridine derivatives as potent EGFR and Src dual inhibitors. Most of the synthesized azaacridines displayed good antiproliferative activity against K562 and A549?cells. The representative compound 13b showed nM IC50 values against K562 and A549?cells, and inhibited EGFR at inhibition rate of 33.53% at 10?μM and Src at inhibition rate of 72.12% at 1?μM. Furthermore, compound 13b could inhibit the expression of EGFR, p-EGFR, Src and p-Src. Moreover, 13b efficiently inhibited the invasion of tumor cells and induced cancer cells apoptosis. Our study suggested that azaacridine scaffold can be developed as novel multi-target kinase inhibitors for cancer therapy.
- Cui, Zhishan,Chen, Shaopeng,Wang, Yanwei,Gao, Chunmei,Chen, Yuzong,Tan, Chunyan,Jiang, Yuyang
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p. 372 - 381
(2017/05/19)
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- Heteroannulation enabled by a bimetallic Rh(III)/Ag(i) relay catalysis: Application in the total synthesis of aristolactam BII
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A redox-neutral bimetallic Rh(iii)/Ag(i) relay catalysis allowed the efficient construction of 3-alkylidene isoindolinones and 3-alkylidene isobenzofuranones. The Rh(iii) catalyst was responsible for the C-H monofluoroalkenylation reaction, whereas the Ag(i) salt was an activator for the follow-up cyclization. The methodology developed was applied as a key step in the rapid total synthesis of the natural product aristolactam BII.
- Ji, Wei-Wei,Lin,Li, Qingjiang,Wang, Honggen
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supporting information
p. 5665 - 5668
(2017/07/07)
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- Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents
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Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100?μg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.
- Sonawane, Amol D.,Rode, Navnath D.,Nawale, Laxman,Joshi, Rohini R.,Joshi, Ramesh A.,Likhite, Anjali P.,Sarkar, Dhiman
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p. 200 - 209
(2017/07/13)
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- Design, Synthesis, and Biological Evaluation of Tetrahydroisoquinoline-Based Histone Deacetylase 8 Selective Inhibitors
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Histone deacetylase 8 (HDAC8) is a promising drug target for multiple therapeutic applications. Here, we describe the modeling, design, synthesis, and biological evaluation of a novel series of C1-substituted tetrahydroisoquinoline (TIQ)-based HDAC8 inhibitors. Minimization of entropic loss upon ligand binding and use of the unique HDAC8 "open" conformation of the binding site yielded a successful strategy for improvement of both HDAC8 potency and selectivity. The TIQ-based 3g and 3n exhibited the highest 82 and 55 nM HDAC8 potency and 330- and 135-fold selectivity over HDAC1, respectively. Selectivity over other class I isoforms was comparable or better, whereas inhibition of HDAC6, a class II HDAC isoform, was below 50% at 10 μM. The cytotoxicity of 3g and 3n was evaluated in neuroblastoma cell lines, and 3n displayed concentration-dependent cytotoxicity similar to or better than that of PCI-34051. The selectivity of 3g and 3n was confirmed in SH-SY5Y cells as both did not increase the acetylation of histone H3 and α-tubulin. Discovery of the novel TIQ chemotype paves the way for the development of HDAC8 selective inhibitors for therapeutic applications.
- Taha, Taha Y.,Aboukhatwa, Shaimaa M.,Knopp, Rachel C.,Ikegaki, Naohiko,Abdelkarim, Hazem,Neerasa, Jayaprakash,Lu, Yunlong,Neelarapu, Raghupathi,Hanigan, Thomas W.,Thatcher, Gregory R. J.,Petukhov, Pavel A.
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supporting information
p. 824 - 829
(2017/08/16)
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- C-H and N-H Bond Annulation of Benzamides with Isonitriles Catalyzed by Cobalt(III)
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A simple efficient, atom-economical procedure was developed for the cobalt-catalyzed C-H bond annulation of benzamides with isonitriles under mild conditions. The reaction tolerates a variety of functional group including heterocycles. Diverse 3-(alkylimino)-2-quinolin-8-yl-2,3-dihydro-1 H -isoindol-1-ones were synthesized using isonitriles as the C1 source through C-H and N-H bond annulation via C-H bond activation in a 'green' solvent. Vinylamides were also used similarly with tert -butyl isonitrile to give 3-(tert -butylimino)-1-quinolin-8-yl-1 H -pyrrol-2(5 H)-ones.
- Kalsi, Deepti,Barsu, Nagaraju,Dahiya, Pardeep,Sundararaju, Basker
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supporting information
p. 3937 - 3944
(2017/08/29)
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- Ruthenium-Catalyzed Difluoroalkylation of 8-Aminoquinoline Amides at the C5-Position
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A ruthenium-catalyzed highly selective difluoromethylation of 8-aminoquinoline amides at the C5 position has been developed. It tolerates a broad range of functional groups, providing the corresponding difluoromethylated products in moderate to good yields. Preliminary experimental results indicate that the tricoordinate ruthenium intermediate is the key factor in achieving the C5-position selectivity.
- Chen, Changpeng,Zeng, Runsheng,Zhang, Jingyu,Zhao, Yingsheng
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supporting information
p. 6947 - 6950
(2017/12/26)
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- METHOD FOR PREPARATION OF CARBOXYLIC ACID CHLORIDES FROM METHYL KETONES WITH TWO REAGENTS
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The invention discloses a method for the preparation of carboxylic acid chlorides starting from methyl ketones with a sulfur chloride and a chlorinating reagent.
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Page/Page column 34-35
(2017/01/26)
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- Expedient Iron-Catalyzed C-H Allylation/Alkylation by Triazole Assistance with Ample Scope
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Triazole assistance set the stage for a unified strategy for the iron-catalyzed C-H allylation of arenes, heteroarenes, and alkenes with ample scope. The versatile catalyst also proved competent for site-selective methylation, benzylation, and alkylation with challenging primary and secondary halides. Triazole-assisted C-H activation proceeded chemo-, site-, and diastereo-selectively, and the modular TAM directing group was readily removed in a traceless fashion under exceedingly mild reaction conditions. One for all: A unified strategy for iron-catalyzed C-H allylation and alkylation was developed by the use of a triazole directing group that could be cleaved under exceedingly mild conditions.
- Cera, Gianpiero,Haven, Tobias,Ackermann, Lutz
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supporting information
p. 1484 - 1488
(2016/02/12)
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- Chelation-Assisted Nickel-Catalyzed Oxidative Annulation via Double C-H Activation/Alkyne Insertion Reaction
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A nickel/NHC system for regioselective oxidative annulation by double C-H bond activation and concomitant alkyne insertion is described. The catalytic reaction requires a bidentate directing group, such as an 8-aminoquinoline, embedded in the substrate. Various 5,6,7,8-tetrasubstituted-N-(quinolin-8-yl)-1-naphthamides can be prepared as well as phenanthrene and benzo[h]quinoline amide derivatives. Diarylalkynes, dialkylalkynes, and arylalkylalkynes can be used in the system. A Ni0/NiII catalytic cycle is proposed as the main catalytic cycle. The alkyne plays a double role as a two-component coupling partner and as a hydrogen acceptor. In two shakes: Oxidative annulation by a double C-H activation/alkyne insertion reaction was achieved by a nickel/NHC system. A Ni0/NiII catalytic cycle is proposed as the main catalytic cycle. The alkyne plays a double role as a two-component coupling partner and as a hydrogen acceptor.
- Misal Castro, Luis C.,Obata, Atsushi,Aihara, Yoshinori,Chatani, Naoto
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supporting information
p. 1362 - 1367
(2016/01/25)
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- Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide–hydrazone and carboxamide moiety
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A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide–hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50values of 2.21?μg/mL, 1.67?μg/mL and 1.11?μg/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide–hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest.
- He, Haifeng,Wang, Xiaoyan,Shi, Liqiao,Yin, Wenyan,Yang, Ziwen,He, Hongwu,Liang, Ying
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supporting information
p. 3263 - 3270
(2016/07/12)
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- Synthesis and biological activity of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives
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A series of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives were designed and synthesized. Their structures were confirmed by1H NMR,13C NMR and HRMS. All title compounds were evaluated for their herbicidal and antifungal activities. Preliminary bioassay results indicated that the title compounds showed good to moderate herbicidal activity at 1000?mg/L. Compound 6q presented the best activity against Digitaria sanguinalis (L) Scop., Amaranthus retroflexus L. and Arabidopsis thaliana with an inhibition degree of five. Compound 6d also showed an inhibition degree of five against D. sanguinalis. In addition, at 50?mg/L, most compounds exhibited good in vitro antifungal activity against Sclerotinia sclerotiorum, with compound 6c showing over 90% antifungal activity against S. sclerotiorum and Pellicularia sasakii.
- Huo, Jing-Qian,Ma, Liu-Yong,Zhang, Zhe,Fan, Zhi-Jin,Zhang, Jin-Lin,Beryozkina, Tetyana V,Bakulev, Vasiliy A
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p. 1547 - 1550
(2016/09/23)
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- From Lead to Drug Candidate: Optimization of 3-(Phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine Derivatives as Agents for the Treatment of Triple Negative Breast Cancer
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Herein we report the sophisticated process of structural optimization toward a previously disclosed Src inhibitor, compound 1, which showed high potency in the treatment of triple negative breast cancer (TNBC) both in vitro and in vivo but had considerable toxicity. A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives were synthesized. In vitro cell-based phenotypic screening together with in vivo assays and structure-activity relationship (SAR) studies finally led to the discovery of N-(3-((4-amino-1-(trans-4-hydroxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)ethynyl)-4-methylphenyl)-4-methyl-3-(trifluoromethyl)benzamide (13an). 13an is a multikinase inhibitor, which potently inhibited Src (IC50 = 0.003 μM), KDR (IC50 = 0.032 μM), and several kinases involved in the MAPK signal transduction. This compound showed potent anti-TNBC activities both in vitro and in vivo, and good pharmacokinetic properties and low toxicity. Mechanisms of action of anti-TNBC were also investigated. Collectively, the data obtained in this study indicate that 13an could be a promising drug candidate for the treatment of TNBC and hence merits further studies.
- Zhang, Chun-Hui,Chen, Kai,Jiao, Yan,Li, Lin-Li,Li, Ya-Ping,Zhang, Rong-Jie,Zheng, Ming-Wu,Zhong, Lei,Huang, Shen-Zhen,Song, Chun-Li,Lin, Wan-Ting,Yang, Jiao,Xiang, Rong,Peng, Bing,Han, Jun-Hong,Lu, Guang-Wen,Wei, Yu-Quan,Yang, Sheng-Yong
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supporting information
p. 9788 - 9805
(2016/11/19)
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- METHOD FOR PREPARATION OF CARBOXYLIC ACID CHLORIDES FROM METHYL KETONES
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The invention discloses a method for the preparation of carboxylic acid chlorides starting from methyl ketones with a sulfur chloride.
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Page/Page column 31
(2017/01/02)
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- Visible-Light-Mediated Synthesis of Amides from Aldehydes and Amines via in Situ Acid Chloride Formation
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An efficient visible-light photocatalysis-based one-pot amide synthesis method was developed; visible-light irradiation of a mixture of an aldehyde, tert-butyl hydrogen peroxide, and N-chlorosuccinimide using a Ru(bpy)3Cl2 photocatalyst afforded an acid chloride, which subsequently reacted with amine to yield the corresponding amide. The reaction was used to synthesize moclobemide and a D3 receptor intermediate.
- Iqbal, Naeem,Cho, Eun Jin
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p. 1905 - 1911
(2016/03/15)
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- Direct arylation of imidazo[1,5-a]azines through ruthenium and palladium catalysis
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The regioselective RuII-catalyzed direct ortho-arylation of C- 3 aryl-substituted imidazo[1,5-a]azines with (hetero)aryl halides was investigated. The employment of RuII and PdII catalysts in the same flask resulted in two sequential and distinct C-H bond arylations, which allowed the rapid synthesis of highly conjugated compounds.
- Roman, Daniela Sustac,Poiret, Valentin,Pelletier, Guillaume,Charette, Andr B.
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supporting information
p. 67 - 71
(2015/02/19)
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- Ligand-promoted ortho-C-H amination with Pd catalysts
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2,4,6-Trimethoxypyridine is identified as an efficient ligand for promoting a Pd-catalyzed ortho-C-H amination of both benzamides and triflyl-protected benzylamines. This finding provides guidance for the development of ligands that can improve or enable PdII-catalyzed Csp2-H activation reactions directed by weakly coordinating functional groups.
- Zhu, Dajian,Yang, Guoqiang,He, Jian,Chu, Ling,Chen, Gang,Gong, Wei,Chen, Ke,Eastgate, Martin D.,Yu, Jin-Quan
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supporting information
p. 2497 - 2500
(2015/02/19)
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- Nickel-catalyzed directed sulfenylation of sp2 and sp3 C-H bonds
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Directed sulfenylation of both sp2 and sp3 C-H bonds was achieved through nickel catalyzed directed C-S bond formation, giving the desired product in good to excellent yield (up to 90%). Other metal cations, including Cu, Fe, Pd, Rh, Ru and Co, gave almost no reaction under identical conditions, which highlighted the unique reactivity of this Ni system.
- Ye, Xiaohan,Petersen, Jeffrey L.,Shi, Xiaodong
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supporting information
p. 7863 - 7866
(2015/05/13)
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- Carboxylate Assisted Ni-Catalyzed C-H Bond Allylation of Benzamides
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A one-step synthetic method was developed for allylation of benzamides using Ni(COD)2/RCO2H and [Ni(μ-H2O)(OOCCMe3)2(HOOCCMe3)2]2 (A′) catalytic system. Efficient, well-defined, air and moisture-stable Ni-pivalate complex was isolated and employed in catalytic allylation. The influence of solvent on product selectivity was also investigated. Nickel-back: A one-step synthetic method was developed for the allylation of benzamides using in situ formed nickel carboxylate Ni(COD)2/RCO2H catalyst (see scheme). The air and moisture stable Ni-pivalate complex was isolated and employed in catalytic allylation. The influence of solvent on product selectivity is discussed.
- Barsu, Nagaraju,Kalsi, Deepti,Sundararaju, Basker
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supporting information
p. 9364 - 9368
(2015/06/30)
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- 1H-1,8- NAPHTHYRIDIN-2ONES AS ANTI PROLIFERATIVE COMPOUNDS
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The present invention relates to novel antiproliferative1H-1, 8-naphthyridin-2-ones of the general formula (I) or pharmaceutically acceptable salts thereof: In which the variable groups are as defined herein, and their preparation and use in therapeutic treatment of disorders related to inhibition of tyrosine kinases in warm blooded animals. The compounds can overcome imatinib induced drug resistance.
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Page/Page column 38
(2015/12/30)
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- Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity
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Bruton's tyrosine kinase (Btk) is an attractive drug target for treating several B-cell lineage cancers. Ibrutinib is a first-in-class covalent irreversible Btk inhibitor and has demonstrated impressive effects in multiple clinical trials. Herein, we present a series of novel 2,5-diaminopyrimidine covalent irreversible inhibitors of Btk. Compared with ibrutinib, these inhibitors exhibited a different selectivity profile for the analyzed kinases as well as a dual-action mode of inhibition of both Btk activation and catalytic activity, which counteracts a negative regulation loop for Btk. Two compounds from this series, 31 and 38, showed potent antiproliferative activities toward multiple B-cell lymphoma cell lines, including germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) cells. In addition, compound 31 significantly prevented tumor growth in a mouse xenograft model.
- Li, Xitao,Zuo, Yingying,Tang, Guanghui,Wang, Yan,Zhou, Yiqing,Wang, Xueying,Guo, Tianlin,Xia, Mengying,Ding, Ning,Pan, Zhengying
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supporting information
p. 5112 - 5128
(2014/07/08)
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- Copper-mediated ortho-nitration of (hetero)arenecarboxylates
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Various (hetero)arenecarboxylic acids were converted to the corresponding Daugulis amides and nitrated selectively in the ortho-position in the presence of [CuNO3(PPh3)2] and AgNO2 at 50 °C. A microwave-assisted saponification allows regenerating the carboxylate group within minutes, which may then be removed tracelessly by protodecarboxylation, or substituted by aryl- or alkoxy-groups via decarboxylative cross-coupling.
- Katayev, Dmitry,Pfister, Kai F.,Wendling, Timo,Goossen, Lukas J.
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supporting information
p. 9902 - 9905
(2014/08/18)
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- KINASE INHIBITOR AND METHOD FOR TREATMENT OF RELATED DISEASES
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Disclosed is a compound of (aminophenylamino) pyrimidyl benzamides and a synthesis method thereof. The compound has Btk-inhibition activity and can be used to treat autoimmune diseases, heteroimmune diseases, cancers or thromboembolic diseases.
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Paragraph 0084; 0085
(2014/09/17)
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- Cu(II)-mediated ortho C-H alkynylation of (hetero)arenes with terminal alkynes
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Cu(II)-promoted ortho alkynylation of arenes and heteroarenes with terminal alkynes has been developed to prepare aryl alkynes. A variety of arenes and terminal alkynes bearing different substituents are compatible with this reaction, thus providing an alternative disconnection to Sonogashira coupling.
- Shang, Ming,Wang, Hong-Li,Sun, Shang-Zheng,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 11590 - 11593
(2014/10/15)
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- Direct allylation of aromatic and α,β-unsaturated carboxamides under ruthenium catalysis
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The ruthenium-catalyzed oxidative allylation of aromatic and α,β-unsaturated carboxamides with allylic carbonates is described. These transformations proceed readily with complete linear γ-selectivity of substituted allylic carbonates. the Partner Organisations 2014.
- Kim, Mirim,Sharma, Satyasheel,Mishra, Neeraj Kumar,Han, Sangil,Park, Jihye,Kim, Minyoung,Shin, Youngmi,Kwak, Jong Hwan,Han, Sang Hoon,Kim, In Su
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supporting information
p. 11303 - 11306
(2014/11/07)
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- Ni(II)-catalyzed oxidative coupling between C(sp2)-H in benzamides and C(sp3)-H in toluene derivatives
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Oxidative coupling between C(sp2)-H bonds and C(sp3)-H bonds is achieved by the Ni(II)-catalyzed reaction of benzamides containing an 8-aminoquinoline moiety as the directing group with toluene derivatives in the presence of heptafluoroisopropyl iodide as the oxidant. The method has a broad scope and shows high functional group compatibility. Toluene derivatives can be used as the coupling partner in an unreactive solvent.
- Aihara, Yoshinori,Tobisu, Mamoru,Fukumoto, Yoshiya,Chatani, Naoto
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supporting information
p. 15509 - 15512
(2014/12/11)
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