- Asymmetric total synthesis of four bioactive lignans using donor-acceptor cyclopropanes and bioassay of (?)- and (+)-niranthin against hepatitis B and influenza viruses
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The asymmetric total synthesis of four lignans, dimethylmatairesinol, matairesinol, (?)-niranthin, and (+)-niranthin has been achieved using reductive ring-opening of cyclopropanes. Moreover, we performed bioassays of the synthesized (+)- and (?)-niranthins using hepatitis B and influenza viruses, which revealed the relationship between the enantiomeric structure and the anti-viral activity of niranthin.
- Karasawa, Daichi,Nishii, Yoshinori,Oshima, Mizuki,Ota, Ryotaro,Shimasaki, Noriko,Watashi, Koichi
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p. 4635 - 4639
(2022/02/19)
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- Incorporation of catechyl monomers into lignins: Lignification from the non-phenolic end: Via Diels-Alder cycloaddition?
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Canonical lignification occurs via the coupling of phenolic radicals, in which chain extension can occur only from phenolic ends of growing polymer chains. Radical coupling of catechyl monomers, including caffeyl and 5-hydroxyconiferyl alcohols, gives ris
- Ando, Daisuke,Boerjan, Wout,Elder, Thomas J.,Eugene, Alexis,Kim, Hoon,Lu, Fachuang,Ralph, John,Tobimatsu, Yuki,Vanholme, Ruben
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p. 8995 - 9013
(2021/11/27)
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- Synthesis method of 2-bromo-3, 4-methylenedioxy-5-methoxybenzoic acid methyl ester
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The invention belongs to the field of chemical pharmacy, and specifically discloses a preparation method of 2-bromo-3, 4-methylenedioxy-5-methoxybenzoic acid methyl ester. The preparation method comprises the following steps: by taking gallic acid as a ra
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Paragraph 0024; 0026
(2020/05/01)
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- Synthetic method of bifendate intermediate
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The invention belongs to the field of chemical pharmacy, and particularly discloses a synthesis method of a bifendate intermediate, and the method comprises the following steps: by using gallic acid as a raw material, carrying out esterification reaction
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Paragraph 0016-0017; 0021-0022; 0026-0027
(2020/04/22)
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- Design and synthesis of novel parabanic acid derivatives as anticonvulsants
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In this work a set of novel derivatives of parabanic acid 9a-d, 12a-d and 13a-d was synthesized and their anticonvulsant potential was evaluated. All the compounds under investigation exhibited anticonvulsant activity in both scPTZ and MES tests. In phase II anticonvulsant study, the trimethoxy phenyl derivative 9a evoked the highest potency among the tested compounds in scPTZ test. It displayed 1.72- and 17.05-folds activity more than the standard drugs phenobarbital and ethosuximide, respectively. In addition, the margin of safety for compound 9a is better than that of the reference antiepileptic drug ethosuximide. Also, compound 9a was devoid of hepatotoxicity indicated by measurements of serum level of ALT, AST, ALP, albumin and total protein. Furthermore, treatment with compound 9a significantly increased the GABA brain level by 2.56-folds compared to the control value. Additionally, molecular docking was performed on the active site of GABA-AT to clarify the interactions of the most potent compound 9a with the enzyme. In MES test, compound 12a exhibited the most potent activity against electric stimuli-induced seizures with the lowest ED50 = 13.7 mg/kg and protective index >36.5. Both candidates 9a and 12a could be a good starting point to develop new molecules as novel antiepileptic drugs.
- Aboutabl, Mona Elsayed,Hassan, Rasha Mohamed,El-Azzouny, Aida Abdel-Sattar,Aboul-Enein, Mohamed Nabil,Abd-Allah, Walaa Hamada
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supporting information
(2019/12/24)
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- Design, synthesis and anticancer evaluation of novel 1,3-benzodioxoles and 1,4-benzodioxines
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A new set of 1,3-benzodioxoles and 1,4-benzodioxines was designed and synthesized starting from gallic acid as anticancer agents. The antiproliferative effect of the target compounds was evaluated against a panel of cancer cell lines (HepG2, PC-3, MCF-7 and A549) using MTT assay. The 1,4-benzodioxine derivative 11a manifested broad spectrum effect towards the four tested cancer cell lines (IC50 50 = 6.37 μM. Also, flow cytometeric analysis revealed that compound 11a could induce both early and late stage apoptosis in MCF-7 cell line. Moreover, the ability of this compound to stimulate apoptosis in the latter cell line was further confirmed by: increment of Bax/Bcl-2 ratio, increase the expression of tumor suppressor gene p53, boosting the levels of initiator and executioner caspases as well as raise in the amount of cytochrome C. In addition molecular docking study was accomplished on the colchicine binding site of tubulin (pdb: 1SA0) to illustrate the interactions of the most potent compound 11a to the receptor.
- Abd-Allah, Walaa Hamada,Aboul-Enein, Mohamed Nabil,El-Azzouny, Aida Abdel-Sattar,Hassan, Rasha Mohamed,Salman, Asmaa Mohamed
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- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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Paragraph 1556
(2015/09/22)
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- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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- Supramolecular gelation of alcohol and water by synthetic amphiphilic gallic acid derivatives
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The supramolecular organogelation of alcohols was observed in relatively hydrophobic amphiphiles with a short oligo(ethylene glycol) unit and three long alkyl chains at room temperature, while the hydrogelation occurred in more hydrophilic gelators with a longer poly(ethylene glycol) unit and two long alkyl chains at various temperatures. When a hot aqueous solution of some of the synthetic hydrogelators was cooled down, the supramolecular hydrogel was formed at room temperature. In some other amphiphiles with less intermolecular interactivity in water at room temperature, a reverse phase transition of sol to gel was observed by elevating the temperature of their aqueous systems, especially below a physiological temperature, 37 °C. The supramolecular hydrogelation at a low or high temperature was dependent on a slight molecular modification of the synthetic amphiphiles.
- Tamiaki, Hitoshi,Ogawa, Keishiro,Enomoto, Keisuke,Taki, Kazutaka,Hotta, Atsushi,Toma, Kazunori
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supporting information; experimental part
p. 1661 - 1666
(2010/04/24)
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- Isolation, synthesis, and neurite outgrowth-promoting activity of illicinin A from the flowers of Illicium anisatum
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Two new prenylated C6-C3 compounds, illicinin A (1) and (4S)-illicinone I (2), were isolated from the flowers of Illicium anisatum. The structures of the new compounds were elucidated by spectroscopic methods. The absolute structure of (4S)-illicinone I was determined by comparing its CD spectrum and specific rotation with those of (4S)-illicinone A (4). Illicinin A (1) and 4-allyl-2,6-dimethoxy-3-(3-methylbut-2-enyl)phenol (3) were found to exhibit neurite outgrowth-promoting activity at concentrations ranging from 0.1 to 10 μM in primary cultured rat cortical neurons. Illicinin A and its derivatives were synthesized for structure-activity relationship studies by employing sequential Stille reactions to introduce a prenyl and an allyl group to the benzene ring, thereby indicating that an allylphenyl moiety in the molecule of 1 is essential for its neurotrophic properties.
- Takaoka, Shigeki,Takaoka, Noriko,Minoshima, Yuka,Huang, Jian-Mei,Kubo, Miwa,Harada, Kenichi,Hioki, Hideaki,Fukuyama, Yoshiyasu
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experimental part
p. 8354 - 8361
(2009/12/26)
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- Synthesis of unsymmetrical biphenyls as potent cytotoxic agents
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Twenty-six unsymmetrical biphenyls were synthesized and evaluated for cytotoxic activity against DU145, A549, KB and KB-Vin tumor cell lines. Three compounds 27, 35 and 40 showed very potent activity against the HTCL panel with an IC50 value range of 0.04-3.23 μM. In addition, fourteen active compounds were all more potent against the drug-resistant KB-Vin cell line than the parental KB cell line. Preliminary SAR analysis indicated that two bulky substituents on the 2,2′-positions of unsymmetrical biphenyl skeleton are necessary and crucial for in vitro anticancer activity, thus providing a good starting point to develop unsymmetrical biphenyls as novel anticancer agents.
- Wu, Gang,Guo, Huan-Fang,Gao, Kun,Liu, Yi-Nan,Bastow, Kenneth F.,Morris-Natschke, Susan L.,Lee, Kuo-Hsiung,Xie, Lan
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scheme or table
p. 5272 - 5276
(2009/05/07)
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- Modulators of ATP-binding cassette transporters
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Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
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Page/Page column 88
(2008/06/13)
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- Synthesis and anti-proliterative in-vitro activity of two natural dihydrostilbenes and their analogues
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A total synthetic route for two natural dihydrostilbenes with significant cytotoxicity toward human cancer cell lines, (3-(2-(7-methoxybenzo[d][1,3] dioxol-5-yl)ethyl)phenol 1a and 6-(3-hydroxyphenethyl)benzo[d][1,3]dioxol-4-ol 1b), which were isolated from Bulbophyllum odoratissimum Lind1, was developed via Wittig-Horner reaction. The natural products 1a and 1b were obtained in 28% and 20% overall yield, respectively. Additionally, nine analogues, 1c-1k, of the two natural dihydrostilbenes were synthesized and evaluated for their anti-proliferative activity against human SGC-7901, KB and HT-1080 cell lines by MTT assay. The activities of 1c and 1d were in the same range as those of the natural products 1a and 1b.
- Zhang, Wei-Ge,Zhao, Rui,Ren, Jian,Ren, Li-Xiang,Lin, Jin-Guang,Liu, Dai-Lin,Wu, Ying-Liang,Yao, Xin-Sheng
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p. 244 - 250
(2008/02/09)
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- Chemical defense of the crust fungus Aleurodiscus amorphus by a tailor-made cyanogenic cyanohydrin ether
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(Chemical Equation Presented) A mighty midget! When injured, the crust fungus A. amorphus (left in the picture) releases hydrocyanic acid by an oxidative mechanism so far unknown in nature. In contrast to cyanogenic glycosides in which the smooth hydrolysis of the glycoside bond is essential for the liberation of hydrocyanic acid, in aleurodisconitrile the oxidation-prone aromatic moiety enables the release of hydrocyanic acid.
- Kindler, Bernhard L. J.,Spiteller, Peter
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p. 8076 - 8078
(2008/09/17)
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- DPPH (=2,2-diphenyl-1-picrylhydrazyl=2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl) radical-scavenging reaction of protocatechuic acid esters (=3,4-dihydroxybenzoates) in alcohols: Formation of bis-alcohol adduct
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Protocatechuic acid esters (=3,4-dihydroxybenzoates) scavenge ca. 5 equiv. of radical in alcoholic solvents, whereas they consume only 2 equiv. of radical in nonalcoholic solvents. While the high radical-scavenging activity of protocatechuic acid esters in alcoholic solvents as compared to that in nonalcoholic solvents is due to a nucleophilic addition of an alcohol molecule at C(2) of an intermediate o-quinone structure, thus regenerating a catechol (=benzene-l,2-diol) structure, it is still unclear why protocatechuic acid esters scavenge more than 4 equiv. of radical (C(2) refers to the protocatechuic acid numbering). Therefore, to elucidate the oxidation mechanism beyond the formation of the C(2) alcohol adduct, 3,4-dihydroxy-2-methoxybenzoic acid methyl ester (4), the C(2) MeOH adduct, which is an oxidation product of methyl protocatechuate (1) in MeOH, was oxidized by the DPPH radical (=2,2-diphenyl-1-picrylhydrazyl) or o-chloranil (=3,4,5,6-tetrachlorocyclohexa- 3,5-diene-1,2-dione) in CD3-OD/(D6)acetone 3:1). The oxidation mixtures were directly analyzed by NMR. Oxidation with both the DPPH radical and o-chloranil produced a C(2),C(6) bis-methanol adduct (7), which could scavenge additional 2 equiv. of radical. Calculations of LUMO electron densities of o-quinones corroborated the regioselective nucleophilic addition of alcohol molecules with o-quinones. Our results strongly suggest that the regeneration of a catechol structure via a nucleophilic addition of an alcohol molecule with a o-quinone is a key reaction for the high radical-scavenging activity of protocatechuic acid esters in alcoholic solvents.
- Saito, Shizuka,Gao, Hong,Kawabata, Jun
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p. 821 - 831
(2007/10/03)
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- Multi-functionalization of gallic acid towards improved synthesis of α- and β-DDB
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The synthesis of mono-, di- and trisubstituted gallic acids and their ester with similar or different groups including different acetal and ketals is described. Regioselective bromination on two ortho-positions of methyl gallate, which is very crucial for many organic syntheses, was achieved in high yield and purity. The α- and β-DDB were synthesized in high overall yield and purity from the regioselective bromoderivatives.
- Alam, Ashraful,Takaguchi, Yutaka,Ito, Hideyuki,Yoshida, Takashi,Tsuboi, Sadao
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p. 1909 - 1918
(2007/10/03)
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- Efficient synthesis of γ-DDB
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Synthesis of γ-DDB, which is another family member of α-DDB (dimethyl 4,4′-dimethoxy-5,6,5′,6 ′- dimethylenedioxybiphenyl-2,2′- dicarboxylate), is described. The unsymmetric isomer (γ-DDB) was constructed by a linker-directed intramolecular Ullmann coupling reaction, followed by the cleavage of the linker and re-esterification.
- Chang, Junbiao,Guo, Xiaohe,Cheng, Senxiang,Guo, Ruiyun,Chen, Rongfeng,Zhao, Kang
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p. 2131 - 2136
(2007/10/03)
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- Synthesis, separation, and theoretical studies of chiral biphenyl lignans (α- and β-DDB)
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Two biphenyl lignans, α- and β-DDB (1 and 2, respectively) were efficiently synthesized without contamination by other regio-isomers. The different yields of the Ullmann coupling reactions for the synthesis of 1 and 2 were rationalized by calculating steric hindrance, stability, entropy change, and heat-of-formation values. The enantiomers of 1 and 2 were readily separated by HPLC on a chiral stationary phase. Their configurations were assigned based on the Cotton effect of the authentic natural products.
- Chang, Junbiao,Chen, Rongfeng,Guo, Ruiyun,Dong, Chunhong,Zhao, Kang
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p. 2239 - 2246
(2007/10/03)
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- Depigmenting activity and low cytotoxicity of alkoxy benzoates or alkoxy cinnamte in cultured melanocytes
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To obtain effective and safe topical depigmenting agents, we synthesized hydroxybenzoates, alkoxybenzoates, and 3,4,5-trimethoxycinnamate containing a thymol moiety and screened then for high-level inhibitory activity against melanin synthesis in cultured melanocytes. Eight compounds were tested for their depigmenting effect and cytotoxicity using a murine melanocyte cell line. We found that 3,4,5-trialkoxybenzoates and 3,4,5-trimethoxycinnamate, synthesized by conjugating 3,4,5-trialkoxybenzoic acids and 3,4,5-trimethoxycinnmic acid with thymol, showed a potent depigmenting effect and low cytotoxicity. Compound 4h, 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate, showed the most potent depigmenting effect (IC50=10 μM) with low cytotoxicity (IC50=200 μM).
- Kang, Hak Hee,Rho, Ho Sik,Hwang, Jae Sung,Oh, Seong-Geon
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p. 1085 - 1088
(2007/10/03)
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- Gallic acid metabolites are markers of black tea intake in humans
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Gallic acid is one of the main phenolic components of black tea. The objective of this study was to identify urinary gallic acid metabolites with potential for use as markers of black tea intake. In an initial study, nine compounds, assessed by using gas chromatography-mass spectrometry, were found to increase in concentration in urine after 3 cups of black tea over 3 h. A subsequent study employed a controlled crossover design in which 10 subjects consumed 5 cups per day of black tea or water for 4 weeks in random order. Twenty-four hour urine samples were collected at the end of each period. Of the 9 candidate compounds identified in the initial study, only 3 were present at higher concentrations in urine of all 10 subjects during tea- drinking in comparison to water-drinking periods. These compounds were identified as 4-O-methylgallic acid, 3-O-methylgallic acid, and 3,4-O- dimethylgallic acid, all methyl ether derivatives of gallic acid. It is suggested that these compounds have the potential to be used as markers of black tea intake.
- Hodgson, Jonathan M.,Morton, Lincoln W.,Puddey, Ian B.,Beilin, Lawrence J.,Croft, Kevin D.
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p. 2276 - 2280
(2007/10/03)
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- Synthetic approach to eusiderin type neolignans
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A general route to synthesis of eusiderin type neolignans has been explored, and exemplified by substituted benzodioxanes IV and XII and conversion of IV to trans-5-methoxy-2-(3,4-dimethoxyphenyl)-3-methyl-7-propylbenzodioxane
- Goyal, Samta,Narula, Pradeep K.,Sharma, Pushpa,Parthasarathy, M. R.
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p. 435 - 439
(2007/10/02)
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- Novel biphenyl derivative and preparation and use thereof
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The present invention relates to a novel biphenyl derivative having a liver ailment-moderating action and effective as a remedy for acute hepatitis and chronic hepatitis, a process for the preparation of this biphenyl derivative and a liver ailment-moderating agent comprising this diphenyl derivative as an effective ingredient. This diphenyl derivative is represented by the following formula: STR1 wherein R0 and R1 independently stand for a lower alkyl group or R0 and R1 together represent a group O=C2 stands for an alkyl group having 1 to 3 carbon atoms, and R3 and R4 independently stand for a hydrogen atom or a lower alkyl group.
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- The total synthesis of (±)-megaphyllone acetate, a cytotoxic neolignan
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Conversion of 3-methoxy-4,5-methylenedioxybenzaldehyde into (2RS,3SR,4RS)-2-methoxycarbonyl-4-(3-methoxy-4,5-methylenedioxyphenyl)-3-m ethyl-4-butanolide was carried out in seven steps via 1-acetoxy-1-(3-methoxy-4,5-methylenedioxyphenyl)propanone. The butanolide was further converted into (2RS,3SR,3aRS,5RS)-3,3a,4,5-tetrahydro-5-methoxy-2-(3-methoxy-4,5-methylen edioxyphenyl)-3-methyl-3a-(2-propenyl)-6(2H)-benzofuranone (22) in eight steps. Reduction of 22 with lithium aluminium hydride followed by acetylation with acetic anhydride in pyridine afforded (±)-megaphyllone acetate.
- Matsumoto,Imai,Yamaguchi,et al.
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p. 346 - 351
(2007/10/02)
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