- FLUORESCENT SYSTEMS FOR BIOLOGICAL IMAGING AND USES THEREOF
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The invention relates to compounds of formula I, in which Y, Ar1, Ar2, X, R1 and R2 are defined herein, and to their use in a variety of biological imaging techniques and therapeutic methods. In aspects, the invention relates to conjugates comprising the compounds of formula I and their associated uses and therapeutic uses.
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Page/Page column 26; 28; 40
(2021/02/12)
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- TARGET PROTEIN EED DEGRADATION-INDUCING DEGRADUCER, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DISEASES RELATED TO EED, EZH2, OR PRC2, COMPRISING SAME AS ACTIVE INGREDIENT
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The present invention relates to a target protein degradation-inducing Degraducer, a preparation method thereof, and a pharmaceutical composition for preventing or treating diseases related to EED, EZH2, or PRC2 comprising same as an active ingredient. A novel compound represented by formula 1, according to the present invention is a Degraducer compound that induces degradation of a target protein, i.e., embryonic ectoderm development (EED) or polycomb repressive complex 2 (PRC2), utilizing cereblon E3 ubiquitin ligase, von Hippel-Lindau tumor suppressor (VHL) E3 ubiquitin ligase, mouse double minute 2 homolog (MDM2) E3 ubiquitin ligase, and cellular inhibitor of apoptosis protein 1 (cIAP) E3 ubiquitin ligase, wherein the compound has an aspect of remarkably achieving target protein degradation-inducing activity through a ubiquitin proteasome system (UPS), and therefore there is a useful effect in that it is possible to provide a pharmaceutical composition for preventing or treating diseases or conditions related to a target protein, and a functional health food composition for preventing or improving same, comprising said compound as an active ingredient.
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- PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
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The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
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Page/Page column 91-92; 92
(2019/11/12)
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- Selective monomethyl esterification of linear dicarboxylic acids with bifunctional alumina catalysts
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An environmentally friendly protocol for the selective protection of dicarboxylic acids is reported using methanol as a cheap esterifying agent and alumina as a heterogeneous catalyst; the selectivity of the process has been ascribed to a balanced acidity/basicity of the bifunctional alumina catalyst.
- Santacroce, Veronica,Bigi, Franca,Casnati, Alessandra,Maggi, Raimondo,Storaro, Loretta,Moretti, Elisa,Vaccaro, Luigi,Maestri, Giovanni
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supporting information
p. 5764 - 5768
(2016/11/06)
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- Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents
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Abstract In our study, three series of hydroxamate, 2-aminobenzamide, and trifluoromethyl ketone analogues have been designed and synthesized. The synthesized compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against three human cancer cell lines including A549, NCI-H661, and U937. Most analogues exhibited higher antiproliferative activities against human acute myeloid leukemia cell U937 than the other two human lung cancer cell lines. Furthermore, the compounds were examined against HDAC1, 2, and 8 isoforms. Docking study of compounds 6h, 9b, and 10a suggested that they might bind tightly to the binding pocket of HDAC2 and/or HDAC8. The results suggest that these compounds might have potential as lead compounds for the development of anti-tumor drugs with HDACs inhibitory activities.
- Cai, Jin,Wei, Hongtao,Hong, Kwon Ho,Wu, Xiaoqing,Zong, Xi,Cao, Meng,Wang, Peng,Li, Lushen,Sun, Chunlong,Chen, Bo,Zhou, Gaoxing,Chen, Junqing,Ji, Min
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p. 3457 - 3471
(2015/08/03)
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- Synthesis and biological evaluation of aziridin-1-yl oxime-based vorinostat analogs as anticancer agents
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The suberoyl anilide hydroxamic acid (vorinostat) analogs with the aziridin-1-yl oxime moiety as a possible metal chelating functionality have been synthesized. Their biological activity and stability under physiological conditions have been evaluated. Although some of the synthesized compounds demonstrated high antiproliferative activity against human HT1080 fibrosarcoma (HT1080, IC50 0.3-7.7 μM) comparable to vorinostat (HT1080, IC50 2.4 μM), they showed only weak histone deacetylase inhibition activity in HeLa cell line extracts.
- Nikitjuka, Anna,Shestakova, Irina,Romanchikova, Nadezhda,Jirgensons, Aigars
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p. 647 - 657
(2016/01/15)
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- Improved antiproliferative activity of 1,3,4-thiadiazole-containing histone deacetylase (HDAC) inhibitors by introduction of the heteroaromatic surface recognition motif
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A series of 1,3,4-thiadiazole-containing hydroxamic acids, in accord with the common pharmacophore of histone deacetylase (HDAC) inhibitors (a Zn2+ binding moiety-a linker-a surface recognition motif), was identified as submicromolar HDAC inhibitors by our group. In this study, we continued our efforts to develop 1,3,4-thiadiazole bearing hydroxamate analogues by modifying the surface recognition motif. We found that 1,3,4-thiadiazoles having a heteroaromatic substituent showed better HDAC inhibitory activity in enzymatic assay and higher antiproliferative potency in cellular assay compared to SAHA.
- Guan, Peng,Wang, Lei,Hou, Xuben,Wan, Yichao,Xu, Wenfang,Tang, Weiping,Fang, Hao
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p. 5766 - 5775
(2015/02/02)
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- METHOD OF MANUFACTURE OF OCTANEDIOIC ACID, PRECURSORS, AND DERIVATIVES
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A method for the manufacture of 1,8-octanedioic acid comprises: reacting gamma-valerolactone with an alcohol in the presence of an acid or a base catalyst to provide an alkyl pentenoate, converting the alkyl pentenoate in the presence of a metathesis initiator to provide the dialkyl octenedioate, reacting the dialkyl octenedioate with hydrogen in the presence of a hydrogenation catalyst to provide a dialkyl 1,8-octanedioate and hydrolyzing the dialkyl 1,8-octanedioate to provide the 1,8-octanedioic acid.
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Paragraph 0091; 0092; 0093
(2014/10/04)
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- Design, synthesis and preliminary bioactivity studies of 1,3,4-thiadiazole hydroxamic acid derivatives as novel histone deacetylase inhibitors
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Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer agents, targeting the biological processes including cell cycle, apoptosis and differentiation. In the present study, a series of 1,3,4-thiadiazole based hydroxamic acids were developed as potent HDAC inhibitors. Some of them showed good inhibitory activity in HDAC enzyme assay and potent growth inhibition in some tumor cell lines. Among them, compound 6i (IC50 = 0.089 μM), exhibited better inhibitory effect compared with SAHA (IC50 = 0.15 μM).
- Guan, Peng,Sun, Feng'E,Hou, Xuben,Wang, Feng,Yi, Fan,Xu, Wenfang,Fang, Hao
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experimental part
p. 3865 - 3872
(2012/08/27)
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- Synthesis of long-chain 3-alkylpyrroles bearing terminal carboxy or amino groups
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Two new ω-(1H-pyrrol-3-yl)alkanoic acids 8a,b and the corresponding amines 9a,b were prepared on large scale in 41-51 and 27-39% overall yield, respectively, starting from N-phenylsulfonyl-protected pyrrole. The target compounds contain the desired functional groups for attachment of biomolecules such as proteins. During synthesis, an unprecedented partial reduction of the pyrrole ring with NaBH3CN in glacial AcOH was observed, for which a plausible mechanism is proposed (Scheme 3).
- Freitas, Jose M.,Abrantes, Luisa M.,Darbre, Tamis
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p. 2470 - 2478
(2007/10/03)
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- Novel (3,5-di-tert-butyl-2-hydroxy-phenylcarbamoyl)-alkanoic acids as potent antioxidants
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A series of novel phenolic antioxidants of amphiphilic structure has been synthesized. Investigations into the influence of aliphatic spacer length and nature of a hydrophilic anchor on the antioxidant activity allowed elucidating certain structure requirements for the membrane-addressed antioxidant designing.
- Lodyato, Vladimir I.,Yurkova, Irina L.,Sorokin, Viktor L.,Shadyro, Oleg I.,Dolgopalets, Vladimir I.,Kisel, Mikhail A.
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p. 4253 - 4256
(2007/10/03)
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- An efficient asymmetric synthesis of prostaglandin E1
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An asymmetric total synthesis of Prostaglandin E1 (5) has been achieved in a two-component coupling process. The chiral hydroxycyclopentenone 6 was readily available from furan with 96% ee. The key reaction step was a kinetic enzymatic resolution followed by an in situ inversion. A catalytic asymmetric reduction of the γ-iodo vinyl ketone 19 with the Corey CBS catalyst gave the ω-side chain 7 with >96% ee. Conjugate addition using the reaction with dilithiocyanocuprate followed by mild cleavage of the silyl protective groups and enzymatic hydrolysis of the methyl ester 22 gave (-)-PGE1 5 in high yield.
- Rodriguez, Ana,Nomen, Miguel,Spur, Bernd Werner,Godfroid, Jean-Jacques
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p. 2655 - 2662
(2007/10/03)
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- A new, modulated, oxidative ring cleavage of α-nitrocycloalkanones by Oxone: Synthesis of α,ω-dicarboxylic acids and α,ω-dicarboxylic acid monomethyl esters
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By the appropriate choice of the reaction conditions Oxone produces the ring cleavage of α-nitrocycloalkanones affording good yields of α,ω-dicarboxylic acids and α,ω-dicarboxylic acid monomethyl esters, respectively, regardless the ring size and/or the presence of an alkyl group as substituent.
- Ballini, Roberto,Curini, Massimo,Epifano, Francesco,Marcotullio, Maria Carla,Rosati, Ornelio
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p. 1049 - 1050
(2007/10/03)
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- Pig liver esterase catalyzed hydrolyses of diesters. A new route to the syntheses of achiral half-esters
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Pig liver esterase catalyzed hydrolyses of diesters of alkanes, aromatic and heterocyclic compounds gave high yields of the corresponding half-esters under mild reaction conditions.
- Ager,Prakash
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p. 739 - 742
(2007/10/02)
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- Enzyme-assisted Preparation of Pure Alkanedicarboxylic Acid Monoesters: Chain-length Dependence of Porcine Liver Esterase (PLE)-catalysed Hydrolyses
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Porcine liver esterase (PJE)-catalysed hydrolyses of alkanedicarboxylic esters MeO2C-(CH2)n-CO2Me lead exclusively to pure monoesters if n 8.Using the active site model for PLE an interpretation of these surprising observations is attempted.
- Lobell, Mario,Schneider, Manfred P.
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p. 1713 - 1714
(2007/10/02)
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- Asymmetric synthesis of the macrolide (-)-Aspicilin
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The asymmetric synthesis of 4(S), 5(R), 6(S), 17(R)-(-)-Aspicilin in described. The chiral parts of the molecule were obtained by asymmetric synthesis monitored by a chiral sulfoxide group.
- Solladie,Fernandez,Maestro
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p. 801 - 819
(2007/10/02)
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- Methylation of Alcohols, Phenols, and Carboxylic Acids, and Selective Monomethylation of Diols and Dicarboxylic Acids with Dimethyl Sulfate by Use of Alumina
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Alcohols in cyclohexane give their methyl ethers in high yields by the use of a combination of dimethyl sulfate and alumina.Some diols and dicarboxylic acids adsorbed on alumina react with dimethyl sulfate and produce the corresponding monomethyl ethers and esters in high selectivities.
- Ogawa, Haruo,Ichimura, Youko,Chihara, Teiji,Teratani, Shousuke,Taya, Kazuo
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p. 2481 - 2484
(2007/10/02)
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- Synthesis of Tetrahydrofuranic Acids Substituted in Position 2 and 5
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A synthesis of the 3,6-epoxyalkane diacids 9a-d previously detected in human urine is described.
- Kern, Werner,Spiteller, Gerhard
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p. 1168 - 1174
(2007/10/02)
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- SELECTIVE MONOMETHYL ESTERIFICATION OF DICARBOXYLIC ACIDS BY USE OF MONOCARBOXYLATE CHEMISORPTION ON ALUMINA.
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The application of alumina as a solid support affords a new procedure for selective reactions. Although it is difficult to obtain monoesters in the esterification of dicarboxylic acids by conventional methods, dicarboxylic acids adsorbed on alumina selectively form the monoesters. Terephthalic acid (1), isophthalic acid, cis- and trans-1,4-cyclohexanedicarboxylic acids, and aliphatic dicarboxylic acids give the corresponding monomethyl esters quantitatively with diazomethane. On the basis of these results, the authors suggest that dicarboxylic acids are adsorbed on alumina through one of their carboxyl groups, and the carboxyl group not adsorbed on the alumina is esterified selectively. Selective monomethyl esterification of phthalic acid is not successful on alumina, probably as a consequence of the close proximity of the two carboxyl groups and the forced orientation of the second group when one is adsorbed.
- Ogawa,Chihara,Taya
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p. 1365 - 1369
(2007/10/02)
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- Antibacterially Active Substituted Anilides of Carboxylic and Sulfonic Acids
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Anilides of carboxylic and sulfonic acids were prepared and tested for antimicrobial activity.While these anilides were ineffective against Gram-negative organisms, there was good correlation between chemical structure and biological activity against Gram-positive species.Both the nature and position of the benzene ring substituents and the length of the carbon side chain affected the activity and specificity of the compounds.The highest activity was observed when the acyl or sulfuryl moiety had a C7-C9 side chain attached.The CONH and SO2NH bridging groups wereequally effective.The attachment of COOH or COOCH3 groups in the ω-position did not effect activity, but the substitution of the acidic proton of the sulfonamide group by an alkyl group rendered the compound inactive.Six compounds, which were substituted anilides of sulfonic acids, fatty acids, or the analogues α-methylene-substituted acids, were bacteriostatic at 10 ppm against Bacillus cereus, Staphylococcus aureus, Streptococcus faecalis and Lactobacillus plantarum .One of these compounds, 2-hydroxy-5-nitroanilide of α-methylenedecanoic acid, was bactericidal at 1 ppm.
- Linfield, Warner M.,Micich, Thomas J.,Montville, Thomas J.,Simon, John R.,Murray, Ermellina B.,Bistline, Raymond G.
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p. 1741 - 1746
(2007/10/02)
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