- Discovery of novel N-benzylbenzamide derivatives as tubulin polymerization inhibitors with potent antitumor activities
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A series of novel N-benzylbenzamide derivatives were designed and synthesized as tubulin polymerization inhibitors. Among fifty-one target compounds, compound 20b exhibited significant antiproliferative activities with IC50 values ranging from 12 to 27 nM against several cancer cell lines, and possessed good plasma stability and satisfactory physicochemical properties. Mechanism studies demonstrated that 20b bound to the colchicine binding site and displayed potent anti-vascular activity. Notably, the corresponding disodium phosphate 20b-P exhibited an excellent safety profile with the LD50 value of 599.7 mg/kg (i.v. injection), meanwhile, it significantly inhibited tumor growth and decreased microvessel density in liver cancer cell H22 allograft mouse model without obvious toxicity. Collectively, 20b and 20b-P are novel promising anti-tubulin agents with more druggable properties and deserve to be further investigated for cancer therapy.
- Zhu, Huajian,Li, Wenlong,Shuai, Wen,Liu, Yang,Yang, Limei,Tan, Yuchen,Zheng, Tiandong,Yao, Hong,Xu, Jinyi,Zhu, Zheying,Yang, Dong-Hua,Chen, Zhe-Sheng,Xu, Shengtao
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- Copper-Catalyzed Intermolecular C(sp2)-H Amination with Electrophilic O-Benzoyl Hydroxylamines
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A copper-catalyzed intermolecular electrophilic amination of benzamides with O-benzoyl hydroxylamines was achieved with the assistance of an 8-aminoquinolyl group. With this protocol, good compatibility was observed for a variety of aryl amides and hetero
- Rao, Wei-Hao,Li, Qi,Jiang, Li-Li,Deng, Xue-Wan,Xu, Pan,Chen, Fang-Yuan,Li, Ming,Zou, Guo-Dong
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p. 10580 - 10590
(2021/08/20)
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- Catalyst-free photodecarbonylation ofortho-amino benzaldehyde
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It is almost a consensus that decarbonylation of the aldehyde group (-CHO) needs to not only be mediated by transition metal catalysts, but also requires severe reaction conditions (high temperature and long reaction time). In this work, inspired by the “conformational-selectivity-based” design strategy, we broke this consensus and discovered a catalyst-free photodecarbonylation of the aldehyde group. It revealed that decarbonylation can be easily achieved with visible light irradiation by introducing a tertiary amine into theortho-position of the aldehyde group. A diverse array of tertiary amines is tolerated by our photodecarbonylation under mild conditions. Furthermore, the (QM) computations of the mechanism and the experiments on well-designed special substrates revealed that our photodecarbonylation depends on the conformational specificity of the aldehyde group and tertiary amine, and occurs through an unusual [1,4]-H shift and a subsequent [1,3]-H shift.
- Li, Lamei,Wang, Songping,Wei, Wentao,Yan, Ming,Zhou, Jingwei
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supporting information
p. 3421 - 3426
(2020/06/25)
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- N-benzylbenzamide derivatives and preparation method and pharmaceutical application thereof
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The invention relates to the field of pharmaceutical chemistry, discloses N-benzylbenzamide derivatives with antitumor activity and a preparation method thereof, and further discloses pharmaceutical compositions containing the compounds and application of the compounds or pharmaceutical salts thereof or the compositions containing the compounds to preparation of medicines for treating tumors and inhibiting diseases or symptoms related to tubulin activity.
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- Discovery of 2-(pyridin-2-yl)aniline as a directing group for the sp2 C-H bond amination mediated by cupric acetate
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2-(Pyridin-2-yl) aniline was designed as a new, removable directing group in promoting C-H amination mediated by cupric acetate. Employing this auxiliary, the β-C(sp2)-H bonds of benzamide derivatives can be effectively aminated with a variety of amines in moderate to good yields with good functional group tolerance in air. In addition, the quinazolinone derivatives were isolated from the reaction mixture of N-(2-(pyridin-2-yl)phenyl)benzamide with formamide or 5-nitroindole. The corresponding mechanism is discussed. These results indicate that 2-(pyridine-2-yl)aniline can serve as a directing group.
- Zhao, Hong-Yi,Wang, Hui-Yan,Mao, Shuai,Xin, Minhang,Zhang, Hao,Zhang, San-Qi
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p. 6622 - 6631
(2017/08/16)
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- Nickel-Catalyzed Direct Amination of Arenes with Alkylamines
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(Figure Presented) The efficient nickel-catalyzed direct amination of arenes with simple alkylamines has been achieved with the assistance of a bidentate directing group through sp2 C-H bond functionalization. Preliminary mechanistic investigations indicate that the reaction probably proceeds through a NiI/NiIII catalytic pathway.
- Yan, Qiangqiang,Chen, Zhengkai,Yu, Wenlong,Yin, Hong,Liu, Zhanxiang,Zhang, Yuhong
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supporting information
p. 2482 - 2485
(2015/05/27)
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- Discovery of benzoylpiperazines as a novel class of potent and selective GlyT1 inhibitors
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Screening of the Roche compound library led to the identification of the benzoylpiperazine 7 as a structurally novel GlyT1 inhibitor. The SAR which was developed in this series resulted in the discovery of highly potent compounds displaying excellent sele
- Pinard, Emmanuel,Alberati, Daniela,Borroni, Edilio,Fischer, Holger,Hainzl, Dominik,Jolidon, Synese,Moreau, Jean-Luc,Narquizian, Robert,Nettekoven, Matthias,Norcross, Roger D.,Stalder, Henri,Thomas, Andrew W.
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scheme or table
p. 5134 - 5139
(2009/05/26)
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- 2, 3, 4, 5-TETRAHYDRO-1H-[1, 4] BENZODIAZEPINE-3-HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE INHIBITORS
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Compounds having formula (1) are useful in treating disease conditions mediated by matrix metalloproteinases and TACE, such as tumor growth, osteoarthritis, rheumatoid arthritis and degenerative cartilage loss.
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- 2,3,4,5-tetrahydro-1H-(1,4)benzodiazepine-3-hydroxamic acids
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Compounds having the following formula: ? are useful in treating disease conditions mediated by matrix metalloproteinases and TACE, such as tumor growth, osteoarthritis, rheumatoid arthritis and degenerative cartilage loss.
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- Combination of MTP inhibitors or apoB-secretion inhibitors with fibrates for use as pharmaceuticals
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The invention relates to the use of fibrates for lowering the liver toxicity of MTP inhibitors as well as pharmaceutical compositions containing an MTP inhibitor and a fibrate.
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- Heteroarylcarboxylic acid amides, the preparation thereof and their use as pharmaceutical compositions
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A compound of formula wherein: Aa, Ra, X1 to X4, Het, and R5 to R7 are defined as in claim 1, the isomers and the salts thereof, particularly the physiologically acceptable salts thereof, which are valuable inhibitors of the microsomal triglyceride-transfer protein (MTP), medicaments containing these compounds and their use, as well as the preparation thereof.
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- 2,3,4,5-tetrahydro-1H-[1,4]-benzodiazepine-3-hydroxyamic acids
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Compounds are provided having the following formula: wherein R, R1, R2, R3, and R4 are defined in the specification, which have matrix metalloproteinase inhibiting activity.
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