- A Novel Model System for Understanding Anticancer Activity of Hypoxia-Activated Prodrugs
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Reports on the comprehensive factors for design considerations of hypoxia-activated prodrugs (HAPs) are rare. We introduced a new model system composed of a series of highly water-soluble HAPs, providing a platform to comprehensively understand the interaction between HAPs and hypoxic biosystems. Specifically, four kinds of new HAPs were designed and synthesized, containing the same biologically active moiety but masked by different bioreductive groups. Our results demonstrated that the activity of the prodrugs was strongly dependent on not only the molecular structure but also the hypoxic tumor microenvironment. We found the presence of a direct linear relationship between cytotoxicity of the HAPs and the reduction potential of whole molecule/oxygen concentration/reductase expression. Moreover, limited blood vasculature in hypoxic regions was also a critical barrier for effective activation of the HAPs. This study offers a comprehensive insight into understanding the design factors required for HAPs.
- Gao, Fangli,Hu, Xueyan,Huang, Xinglu,Liu, Qiqi,Sun, Zhiyuan,Wei, Yonghua,Wu, Jin,Zhang, Congcong,Zhang, Haoqi,Zhuang, Jie
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- Synthesis of Indole/Benzofuran-Containing Diarylmethanes through Palladium-Catalyzed Reaction of Indolylmethyl or Benzofuranylmethyl Acetates with Boronic Acids
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The palladium-catalyzed synthesis of indole/benzofurancontaining diarylmethanes starting from indolylmethyl or benzofuranylmethyl acetates with boronic acids has been investigated. The success of the reaction is influenced by the choice of precatalyst: with indolylmethyl acetates the reaction works well with [Pd(η3-C3H5)Cl]2/XPhos while with benzofuranylmethyl acetates Pd2(dba)3/XPhos is more efficient. The good to high yields and the simplicity of the experimental procedure make this protocol a versatile synthetic tool for the preparation of 2- and 3-substituted indoles and 2-benzo[b]furans. The methodology can be advantageously extended to the preparation of a key precursor of Zafirlukast.
- Arcadi, Antonio,Calcaterra, Andrea,Chiarini, Marco,Fabrizi, Giancarlo,Fochetti, Andrea,Goggiamani, Antonella,Iazzetti, Antonia,Marrone, Federico,Marsicano, Vincenzo,Serraiocco, Andrea
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supporting information
p. 741 - 753
(2021/11/26)
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- Palladium-catalyzed Tsuji-Trost-type reaction of benzofuran-2-ylmethyl acetates with nucleophiles
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The palladium-catalyzed benzylic-like nucleophilic substitution of benzofuran-2-ylmethyl acetate with N, S, O and C soft nucleophiles has been investigated. The success of the reaction is dramatically influenced by the choice of catalytic system: with nitrogen based nucleophiles the reaction works well with Pd2(dba)3/dppf, while with sulfur, oxygen and carbo-nucleophiles [Pd(η3-C3H5)Cl]2/XPhos is more efficient. The regiochemical outcome shows that the nucleophilic substitution occurs only on the benzylic position of the η3-(benzofuryl)methyl complex. The high to excellent yields and the simplicity of the experimental procedure make this protocol a versatile synthetic tool for the preparation of 2-substituted benzo[b]furans. This journal is
- Arcadi, Antonio,Fabrizi, Giancarlo,Fochetti, Andrea,Ghirga, Francesca,Goggiamani, Antonella,Iazzetti, Antonia,Marrone, Federico,Mazzoccanti, Giulia,Serraiocco, Andrea
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p. 909 - 917
(2021/01/20)
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- Pyridinium-modified prodrug small molecule containing different nitroaromatic heterocycles
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The invention relates to a pyridinium-modified prodrug small molecule containing different nitroaromatic heterocycles. The structural formula is a formula (I), a formula (II) or a formula (III)(pleasesee the see the specification for the formula). A series of novel small molecule hypoxia activated prodrug is synthesized through design, through the screening of synthesized prodrugs, different aromatic heterocyclic modified hypoxia activated prodrugs have different sensitivity to oxygen, and furan-ring-modified prodrug molecule exhibits the best hypoxic toxicity at 3LL, PC-3, HepG2 and B16 at the cellular level. By constructing a mouse lung cancer 3LL cell model and studying anti-tumor activity of the model, it is found that the furan-ring-modified prodrug molecule Q1 can be more effectively inhibit tumor cell proliferation.
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Paragraph 0047-0049
(2019/11/21)
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- Derivatives of Pyrido[2,3-d]pyrimidine, the Preparation Thereof, and the Therapeutic Application of the Same
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The invention relates to derivatives of pyrido[2,3-d]pyrimidine, to the preparation thereof, and to the therapeutic application of the same.
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Page/Page column 5
(2008/12/07)
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- TRIAZOLE DERIVATIVES USEFUL AS AXL INHIBITORS
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Triazole derivatives and pharmaceutical compositions containing the derivatives are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the derivatives in treating diseases or conditions associated with Axl catalytic activity are also disclosed.
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Page/Page column 167-168
(2010/11/26)
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- Benzoxazepinones and their use as squalene synthase inhibitors
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There is disclosed a compound represented by the formula [I]: wherein R1 is optionally substituted 1-carboxyethyl group, optionally substituted alkyl-sulfonyl group, optionally substituted (carboxy-cycloalkyl)-alkyl group, -X1-X2-Ar-X3-X4-COOH (wherein X1 and X4 are a bond or alkylene group, X2 and X3 are a bond, -O-, -S-, Ar is divalent aromatic group etc.), R2 is alkyl group optionally substituted with alkanoyloxy group and/or hydroxy group, R3 is alkyl group, and W is halogen atom, etc., or a salt thereof. The compound has the cholesterol lowering activity and the triglyceride lowering activity and is useful for preventing and/or treating hyperlipidemia.
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- Pd/C mediated synthesis of 2-substituted benzo[b]furans/nitrobenzo[b] furans in water
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An efficient synthesis of 2-alkyl/aryl substituted benzo[b]furans/nitrobenzo[b]furans in water has been accomplished via Pd/C catalyzed reaction of o-iodophenols with terminal alkynes in the presence of PPh3, CuI and prolinol. This method can t
- Pal, Manojit,Subramanian, Venkataraman,Yeleswarapu, Koteswar Rao
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p. 8221 - 8225
(2007/10/03)
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- Aminoalkyl-substituted aromatic bicyclic compounds, methods for their preparation and their use as pharmaceuticals
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The present invention relates to aminoalkyl-substituted aromatic bicyclic compounds of formula I, which are valuable pharmaceutically active compounds that are suitable, for example, for the treatment of obesity, type II diabetes, arteriosclerosis, high blood pressure, paresthesia, depression, anxiety, anxiety neuroses, schizophrenia, disorders associated with the circadian rhythm, and drug abuse, as well as normalizing lipid metabolism.
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