- 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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- New strategy for detection of hydrogen peroxide based on bi-nucleophilic reaction
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Two novel fluorescent probes based on 7-hydroxy-4-methyl-coumarin, FAA-MC-OH (2-fluoro-4-nitro-phenylacetyl hydroxyl coumarin) and FBA-MC-OH (2-fluoro-4-nitro-benzoyl hydroxyl coumarin) are first synthesized, and spectral studies confirm that both the pro
- Liu, Xiang,Mao, Chenxin,Tian, Yafei,Wang, Bei,Wang, Shuoshuo
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supporting information
(2021/07/14)
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- Discovery of novel 2-phenylamino-4-prolylpyrimidine derivatives as TRK/ALK dual inhibitors with promising antitumor effects
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In order to explore novel TRK and ALK dual inhibitors, a series of 2-phenylamino-4-prolylpyrimidine derivatives were designed, synthesized and evaluated for their in vitro cytotoxicity and enzymatic activities. Delightfully, most compounds were detected m
- Cao, Zhi,Guo, Ming,Jiang, Nan,Li, Changtao,Li, Tong,Wang, Xinyu,Yang, Jing,Zhai, Xin
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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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Paragraph 0042-0045
(2019/05/08)
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- 2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONES AND RELATED COMPOUNDS USEFUL AS HIV REPLICATION INHIBITORS
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The present invention relates to compounds and compositions acting as inhibitors of HIV integrase. The compound of the invention is of Formula (I), or a tautomer (I') thereof, or a pharmaceutically acceptable salt, or solvate of said compound or tautomer
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Page/Page column 83
(2012/07/13)
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- A highly selective tandem cross-coupling of gem-dihaloolefins for a modular, efficient synthesis of highly functionalized indoles
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(Chemical Equation Presented) A highly efficient method of indole synthesis using gem-dihalovinylaniline substrates and an organoboron reagent was developed via a Pd-catalyzed tandem intramolecular amination and an intermolecular Suzuki coupling. Aryl, alkenyl, and alkyl boron reagents are all successfully employed, making for a versatile modular approach. The reaction tolerates a variety of substitution patterns on the aniline leading to indoles with group at C2-C7. The orthogonal approach of the sequential copper- and palladium-mediated synthesis of 1,2-diarylindoles exploited the wide availability of diverse organoboron reagents.
- Fang, Yuan-Qing,Lautens, Mark
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p. 538 - 549
(2008/09/17)
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- A novel antibacterial 8-chloroquinolone with a distorted orientation of the N1-(5-amino-2,4-difluorophenyl) group
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Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential. In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones. Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6- fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria. This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus. The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity. An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 Cl atom and the N-1 substituent. Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group. Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.
- Kuramoto, Yasuhiro,Ohshita, Yoshihiro,Yoshida, Jiro,Yazaki, Akira,Shiro, Motoo,Koike, Tohru
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p. 1905 - 1917
(2007/10/03)
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- Synthesis of 7-benzoxazol-2-yl and 7-Benzothiazol-2-yl-6-fluoro- quinolones
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The fluoroquinolones, 7-benzoxazol-2-yl-1-ethyl-6-fluoro-1,4-dihydro-4- oxoquinoline-3-carboxylic acid and 7-benzothiazol-2-yl-1-ethyl-6-fluoro-1,4- dihydro-4-oxoquinoline-3-carboxylic acid, were synthesized. The compounds were obtained, by use of the Gou
- Richardson, Thomas O.,Shanbhag, Vinayak P.,Adair, Kimberly,Smith, Shantel
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p. 1301 - 1304
(2007/10/03)
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- Process for 8-cyano-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acids and intermediates thereof
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A process for preparing 8-cyano-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acids from substituted benzoic acids. Intermediates involved in the process are also described. 8-cyano-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizin
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- Antimicrobial 8-cyano-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acids
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The compounds 8-cyano-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid and 8-cyano-6,7-dihydro-9-fluoro-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid are disclosed as potent antimicrobial agents. Pharmaceutically-acceptable carboxylate salts, esters, acyl chlorides, amides and alkylaminoalkyl ester salts of the acids are also disclosed.
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- Antimicrobial derivatives of 8-amino and 8-aminomethyl benzo(ij)quinolizine
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This invention relates to antimicrobial compounds of the formula STR1 wherein X is hydrogen or fluorine; Y is selected from the group consisting of STR2 and ester, carboxylate salts, and alkylaminoalkyl ester salts thereof.
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- Micellar Catalysis of Nucleophilic Aromatic Substitution Reaction Between Anionic Nucleophiles and Aromatic Substrates Containing Anionic Substituents
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Rate constants for SNAr reactions between anionic nucleophiles and aromatic substrates bearing anionic substituents in the presence and absence of micelles of cetyltrimethylammonium bromide (ctab) have been measured.Micellar catalysis of this class of reaction seems to be of the same order of magnitude as for SNAr reactions between anionic nucleophiles and dipolar organic substrates.Micellar catalysis of SNAr reactions of the ambident nitrite ion has also been studied.The magnitude of catalysis of SNAr reactions of sodium nitrite by micelles of ctab is largecompared to that for SNAr reactions of hydroxide ions or azide ions.This suggests that nitrite ion is well solubilized by micelles of ctab and some consequences of this in biological systems are discussed.The ambident behaviour of nitrite ion in aqueous micellar solution towards organic substrates seems to mirror that in methanolic solution.
- Broxton, Trevor J.
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p. 969 - 979
(2007/10/02)
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