- Polystyrene supported palladium nanoparticles catalyzed cinnamic acid synthesis using maleic anhydride as a substitute for acrylic acid
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Maleic anhydride was explored as a substitute for acrylic acid to synthesize cinnamic acids from aryl halides under heterogeneous palladium catalyzed conditions. The combined role of surface and impregnated catalyst together performed an upright engineering to hold in situ generated molecules on the surface and subsequently facilitate their interaction for the desired product synthesis. Overall, a surface mediated approach for cinnamic acid synthesis from maleic anhydride following a major unexplored pathway through catalyst promoted decarboxylation was critically investigated.
- Thakur, Vandna,Kumar, Sandeep,Das, Pralay
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p. 3692 - 3697
(2017/09/07)
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- Pharmacokinetic optimization of class-selective histone deacetylase inhibitors and identification of associated candidate predictive biomarkers of hepatocellular carcinoma tumor response
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Herein, we describe the pharmacokinetic optimization of a series of class-selective histone deacetylase (HDAC) inhibitors and the subsequent identification of candidate predictive biomarkers of hepatocellular carcinoma (HCC) tumor response for our clinical lead using patient-derived HCC tumor xenograft models. Through a combination of conformational constraint and scaffold hopping, we lowered the in vivo clearance (CL) and significantly improved the bioavailability (F) and exposure (AUC) of our HDAC inhibitors while maintaining selectivity toward the class I HDAC family with particular potency against HDAC1, resulting in clinical lead 5 (HDAC1 IC50 = 60 nM, mouse CL = 39 mL/min/kg, mouse F = 100%, mouse AUC after single oral dose at 10 mg/kg = 6316 h·ng/mL). We then evaluated 5 in a biomarker discovery pilot study using patient-derived tumor xenograft models, wherein two out of the three models responded to treatment. By comparing tumor response status to compound tumor exposure, induction of acetylated histone H3, candidate gene expression changes, and promoter DNA methylation status from all three models at various time points, we identified preliminary candidate response prediction biomarkers that warrant further validation in a larger cohort of patient-derived tumor models and through confirmatory functional studies.
- Wong, Jason C.,Tang, Guozhi,Wu, Xihan,Liang, Chungen,Zhang, Zhenshan,Guo, Lei,Peng, Zhenghong,Zhang, Weixing,Lin, Xianfeng,Wang, Zhanguo,Mei, Jianghua,Chen, Junli,Pan, Song,Zhang, Nan,Liu, Yongfu,Zhou, Mingwei,Feng, Lichun,Zhao, Weili,Li, Shijie,Zhang, Chao,Zhang, Meifang,Rong, Yiping,Jin, Tai-Guang,Zhang, Xiongwen,Ren, Shuang,Ji, Ying,Zhao, Rong,She, Jin,Ren, Yi,He, Yun,Chen, Li,Xu, Chunping,Chen, Dawei,Cai, Jie,Chen, Taiping,Shan, Song,Pan, Desi,Ning, Zhiqiang,Lu, Xianping
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supporting information
p. 8903 - 8925,23
(2020/09/16)
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- ORTHO AMINOAMIDES FOR THE TREATMENT OF CANCER
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Compounds of formula are HDAC inhibitors. These compounds are useful for the treatment of diseases such as cancer in humans or animals.
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Page/Page column 98
(2010/09/05)
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- Polyhalogen-substituted cinnamic acids and cinnamic acid derivatives and a process for the preparation of polyhalogen-substituted cinnamic acids and cinnamic acid derivatives
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Polyhalogenated cinnamic acids and cinnamic acid derivatives are prepared by reacting diazonium salts accessible from polyhalogenated anilines with acrylic acid or acrylic acid derivatives in the presence of a homogeneous, palladium-containing catalyst at about ?5 to about +100° C. Some of the cinnamic acids and cinnamic acid derivatives obtainable in this way are new. Cinnamic acids and cinnamic acid derivatives which can be prepared according to the invention can be used for the preparation of indanones which are precursors for agro- and pharmaceutical chemicals and for substances having liquid-crystalline properties.
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- 3,4-dihydro-4-oxo-3-(2-propenyl)-1-phthalazineacetic acids and derivatives, their preparations and medicines containing them
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Novel 3,4-dihydro-4-oxo-3(prop-2-enyl)-1-phtalazineacetic acids and derivatives of formula (I) STR1 in which R1 R2 and R3 are the same or different and stand for H, a halogen or a linear or branched aliphatic, saturated or unsaturated radical, substituted or not by at least one halogen or R4 residue such as defined below, except when R4 is H; R4 and R5 are the same or different and stand for H, a linear or branched aliphatic radical, saturated or unsaturated, an aryl or heteroaryl radical, said radicals being substituted or not by at least one grouping such as fluorine, chlorine, bromine, methyl or trifluoromethyl, where R4 and R5 do not simultaneously denote H; R6 stands for hydroxy or alkoxy radical; R7 stands for H, a halogen, a linear or branched aliphatic saturated or unsaturated radical, an alkoxy radical, said radicals being substituted or not by analiphatic or halogenated radical, a nitro group, a substituted or unsubstituted amino group, S(O)n R8 or a cyano group; n is equal to 0,1 or 2; R8 is an aliphatic, linear or branched radical, an aryl or heteroaryl radical, an amino radical, said radicals being substituted or not by an aliphatic or halogenated radical. This invention also relates to the optional tautomeric forms of said acids and their pharmaceutically acceptable base addition salts. Also described is a process for preparing said compounds and the drugs containing same.
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