- Design and Synthesis of Novel N-(2-aminophenyl)benzamide Derivatives as Histone Deacetylase Inhibitors and Their Antitumor Activity Study
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Histone deacetylases (HDACs) are promising therapeutic targets for cancer therapy because inhibition of HDACs triggers growth arrest or apoptosis of tumor cells. In the present study, a new series of fluorinated N-(2-aminophenyl)benzamide derivatives were synthesized to investigate potential inhibition of HDACs and associated anticancer activity. Among the synthesized derivatives, compound 24a showed potent inhibitory activity of HDACs and higher antitumor efficacy in human cancer cell lines (HCT-116, MCF-7, and A549) compared with SAHA. Moreover, animal studies demonstrated that compound 24a showed potent in vivo antitumor efficacy in an HCT-116 colon cancer xenograft mouse model.
- La, Minh Thanh,Jeong, Byung-Hoon,Kim, Hee-Kwon
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p. 740 - 743
(2021/03/16)
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- Biocatalytic Construction of Quaternary Centers by Aldol Addition of 3,3-Disubstituted 2-Oxoacid Derivatives to Aldehydes
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The congested nature of quaternary carbons hinders their preparation, most notably when stereocontrol is required. Here we report a biocatalytic method for the creation of quaternary carbon centers with broad substrate scope, leading to different compound classes bearing this structural feature. The key step comprises the aldol addition of 3,3-disubstituted 2-oxoacids to aldehydes catalyzed by metal dependent 3-methyl-2-oxobutanoate hydroxymethyltransferase from E. coli (KPHMT) and variants thereof. The 3,3,3-trisubstituted 2-oxoacids thus produced were converted into 2-oxolactones and 3-hydroxy acids and directly to ulosonic acid derivatives, all bearing gem-dialkyl, gem-cycloalkyl, and spirocyclic quaternary centers. In addition, some of these reactions use a single enantiomer from racemic nucleophiles to afford stereopure quaternary carbons. The notable substrate tolerance and stereocontrol of these enzymes are indicative of their potential for the synthesis of structurally intricate molecules.
- Marín-Valls, Roser,Hernández, Karel,Bolte, Michael,Parella, Teodor,Joglar, Jesús,Bujons, Jordi,Clapés, Pere
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supporting information
p. 19754 - 19762
(2020/12/01)
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- Piperazine adenosine monophosphate activated protein kinase (AMPK) agonist and medical application thereof
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The invention discloses a piperazine compound with AMPK agonist activity, and a preparation method and medical application of the piperazine compound. The piperazine compound is a compound shown as aformula (I) (please see the specifications for the formula), and a pharmaceutically acceptable salt or ester or a prodrug or N-oxide or solvate thereof. The compound can be used for preparing drugs for preventing or treating AMPK-mediated diseases.
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Paragraph 0642; 0644; 0645
(2019/11/12)
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- ISOXAZOLIDINE DERIVED INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE 1 (RIPK 1)
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The present disclosure relates generally to methods and compositions for preventing or arresting cell death and/or inflammation.
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Page/Page column 165
(2017/07/18)
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- O-Benzylation of Carboxylic Acids Using 2,4,6-Tris(benzyloxy)-1,3,5-triazine (TriBOT) under Acidic or Thermal Conditions
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Two methods for the synthesis of benzyl esters from carboxylic acids using the O-benzylating reagent 2,4,6-tris(benzyloxy)-1,3,5-triazine (TriBOT) have been developed. The reactions were conducted either in the presence of a catalytic amount of TfOH at room temperature (acidic conditions) or in the absence of TfOH at 180-230 C (thermal conditions). Interestingly, the O-benzylation of hydroxy carboxylic acids under the two conditions afforded different products: The dibenzylated product under acidic conditions and the hydroxy ester under thermal conditions. In addition to these results, other evidence indicated that the former reaction proceeds through an SN1-type mechanism, and the latter by an SN2-type mechanism. Two methods for the O-benzylation of carboxylic acids using TriBOT have been developed under either acidic or thermal conditions. The O-benzylation of hydroxy carboxylic acids afforded the dibenzylated product under acidic conditions and the hydroxy ester under thermal conditions. The former reaction proceeds through an SN1-type mechanism and the latter by an SN2-type mechanism.
- Yamada, Kohei,Yoshida, Saki,Fujita, Hikaru,Kitamura, Masanori,Kunishima, Munetaka
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p. 7997 - 8002
(2015/12/24)
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- Synthesis of the spiroacetal core of the cephalosporolide family of natural products
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The synthesis of four possible stereoisomers of the spiroacetal core of the natural products cephalosporolides H and I and penisporolides A and B is described. The key steps involve the use of Sharpless asymmetric dihydroxylation to install the desired stereochemistry of the γ-lactone ring and an oxidative radical cyclisation to form the spiroacetal ring system.
- Finch, Orla C.,Furkert, Daniel P.,Brimble, Margaret A.
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p. 590 - 596
(2014/02/14)
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- NOVEL COMPOUND AND MEDICAL USE THEREOF
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Provided is a levodopa prodrug that overcomes the problems attributed to the blood kinetics of levodopa such as large number of doses and the incidence of side effects due to frequent dosing. (2S)-2-Amino-3-(3,4-bis((2-(benzoyloxy)-2-methylpropanoyl)oxy)p
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Paragraph 0391-0394
(2013/09/26)
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- MASKED CARBOXYLATE NEOPENTYL SULFONYL ESTER CYCLIZATION RELEASE PRODRUGS OF ACAMPROSATE, COMPOSITIONS THEREOF, AND METHODS OF USE
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Masked carboxylate neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs
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Page/Page column 45
(2009/04/24)
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- KINASE INHIBITORS
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The present invention provides kinase inhibitors of Formula (I). Wherein R1, R2, X and Z are as described herein, or a pharmaceutically acceptable salt thereof.
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Page/Page column 23-24
(2010/11/27)
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- PYRAZOLE-ISOQUINOLINE UREA DERIVATIVES AS P38 KINASE INHIBITORS
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The present invention provides kinase inhibitors of Formula (I) wherein R1, R2, and X are as described herein, or a pharmaceutically acceptable salt thereof.
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Page/Page column 13
(2008/06/13)
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- ARYL-AMINO SUBSTITUTED PYRROLOPYRIMIDINE MULTI-KINASE INHIBITING COMPOUNDS
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Compounds represented by Formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, are inhibitors of least two of the Abl, Aurora-A, Blk, c-Raf, cSRC, Src, PRK2, FGFR3, Flt3, Lck, Mekl, PDK-1, GSK3?, EGFR, p70S6K, BMX, SGK, CaMKII, Tie-2
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Page/Page column 92-93
(2008/06/13)
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- PYRAZOLE DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, MEDICINAL USE THEREOF, AND INTERMEDIATE FOR PRODUCTION THEREOF
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The present invention provides pyrazole derivatives represented by the general formula: wherein R1 represents H, an optionally substituted C1-6 alkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted C1-6 alkyl group etc.; R2 represents H, a halogen atom, OH, an optionally substituted C1-6 alkyl group etc.; X represents a single bond, O or S; Y represents a single bond, a C1-6 alkylene group etc. ; Z represents CO or SO2; R4 and R5 represent H, an optionally substituted C1-6 alkyl group etc.; and R3, R6 and R7 represent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.
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Page/Page column 43
(2008/06/13)
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- INDOLE COMPOUND AND MEDICINAL USE THEREOF
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An indole compound represented by the formula (1) wherein each symbol is as defined in the specification, a pharmaceutically acceptable salt thereof or a prodrug thereof is useful as a therapeutic agents for diabetes having an HLGPa inhibitory activity.
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- β2,2-aminoxy acids: A new building block for turns and helices
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The conformational properties of peptides 1-4 built from 3-aminoxy-2,2-dimethyl-propionic acid, a β2,2-aminoxy acid, were investigated by NMR spectroscopy and X-ray crystallography. A novel β N-O turn involving a nine-membered-ring intramolecular hydrogen bond between NHi+2 and COi was formed in diamides 1 and 2, which was further stabilized by another six-membered-ring intramolecular hydrogen bond between NHi+2 and NOi+1. Triamides 3 and 4 displayed a well-defined helical structure featuring two consecutive β N-O turns. The X-ray structure of 4 revealed that the amide carbonyl group at position i+2 was twisted +65.9° from that at i position, suggesting a novel 1.79 helix. Therefore, β2,2-aminoxy acid can be used as a new building block for turns and helices. Copyright
- Yang, Dan,Zhang, Yu-Hui,Zhu, Nian-Yong
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p. 9966 - 9967
(2007/10/03)
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- 2-SACCHARINYLMETHYL ARYL CARBOXYLATES USEFUL AS PROTEOLYTIC ENZYME INHIBITORS AND COMPOSITIONS AND METHOD OF USE THEREOF
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A compound having the formula: STR1 wherein Ar, R 4 and R 5 are defined herein have pharmaceutical utility as proteolytic enzyme inhibitors.
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