- Synthesis of Novel 4-(Dimethylaminoalkyl)piperazine-1-carbodithioa t e Derivatives as Cholinesterase Inhibitors
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Background: Carbamate compounds have attracted a great deal of interest in medicinal chemistry due to their inhibition potential against cholinesterase enzymes. Method: Hence, this study was undertaken to synthesize new piperazine derivatives including dithiocarbamate moiety, which is the bioisoster of carbamate. Twenty eight 4-(dimethylaminoalkyl) piperazine-1-carbodithioate derivatives (3a-3n, 4a-4n) were synthesized. Chemical structures of these compounds were confirmed by spectral data. Ellman's assay was applied in order to investigate inhibitory potency of the compounds against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) enzymes. Results and Conclusion: It was determined that some of the compounds have remarkable activity on AChE. ADME (Absorption, distribution, metabolism, elimination) predictions were theoretically performed for all compounds in the series. Enzyme kinetics and molecular docking studies were carried out for the most active compound (3n) and nature of inhibition and interactions between enzyme and ligand were described.
- ?evik, Ulviye Acar,Levent, Serkan,Saglik, Begüm Nurpelin,?zkay, Yusuf,Kaplancikli, Zafer Asim
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- Synthesis and antimicrobial activity evaluation of new dithiocarbamate derivatives bearing thiazole/benzothiazole rings
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The synthesis of 2-(substituted phenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A1-A24) derivatives and 2-(4-substituted thiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B1-B14) derivatives was undertaken starting from the potassium salt of 4-(2-pyrimidinyl)piperazine dithiocarbamate. The structures of the obtained compounds were elucidated by1H NMR,13C NMR, MS spectral data, and elemental analysis. The antimicrobial activity of the thirty eight newly synthesized compounds were tested against 12 microorganism strains using the microdilution technique. Compounds 2-(4-ethoxycarbonylthiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B12), 2-(3-fluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A18) and 2-(3,4-difluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A21) were determined to possess high antimicrobial activity.
- Yurtta?, Leyla,?zkay, Yusuf,Duran, Murat,Turan-Zitouni, Gülhan,?zdemir, Ahmet,Cantürk, Zerrin,Kü?üko?lu, Kaan,Kaplanc?kl?, Zafer As?m
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- Design, synthesis and biological evaluation of flexible and rigid analogs of 4H-1,2,4-triazoles bearing 3,4,5-trimethoxyphenyl moiety as new antiproliferative agents
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Several flexible and rigid analogs of 4H-1,2,4-triazoles (compounds 8a-g and 9a-g) bearing trimethoxyphenyl pharmacophoric unit, were designed and synthesized as potential anticancer agents. The in vitro cytotoxic assay indicated that both flexible and rigid analogs (8 and 9, respectively) can potentially inhibit the growth of cancerous cells (A549, MCF7, and SKOV3), with IC50 values less than 5.0 μM. Furthermore, compounds 10a-l as regional isomers of compounds 9 exhibited remarkable cytotoxic activity with IC50 values ranging from 0.30 to 5.0 μM. The rigid analogs 9a, 10h and 10k were significantly more potent than etoposide against MCF7, SKOV3 and A549 cells, respectively. These compounds showed high selectivity towards cancer cells over normal cells, as they had no significant cytotoxicity against L929 cells. In addition, the representative compounds 9a and 10h could inhibit the tubulin polymerization at micro-molar levels. By determining changes in the colchicine-tubulin fluorescence, it was suggested that compound 10h could bind to the tubulin at the colchicine pocket. The molecular docking study further confirmed the inhibitory activity of promising compounds 9a, 10h and 10k on tubulin polymerization through binding to the colchicine-binding site.
- Ansari, Mahsa,Shokrzadeh, Mohammad,Karima, Saeed,Rajaei, Shima,Hashemi, Seyedeh Mahdieh,Mirzaei, Hassan,Fallah, Marjan,Emami, Saeed
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- Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies
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In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.
- Zhou, You,Lu, Xin,Du, Chenxi,Liu, Yijun,Wang, Yifan,Hong, Kwon Ho,Chen, Yao,Sun, Haopeng
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- BuChE-IDO1 inhibitor as well as preparation method and application thereof
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The invention relates to the field of medicines, and particularly discloses a BuChE-IDO1 inhibitor as well as a preparation method and application thereof. The 7-chlorine-3-substituted benzothiophene part of sertaconazole is chemically modified, the influence of the 7-chlorine-3-substituted benzothiophene part of sertaconazole on the in-vitro inhibitory activity of AChE, BuChE and IDO1 is explored, the target compound is further optimized, and the technical problems that an existing BuChE-IDO1 inhibitor is poor in pertinence and safety are solved. What is explored is that an appropriate substituent group introduced to a 2-benzothiazole ring can form additional interaction with surrounding amino acids and heme iron, so that the binding affinity of the analogue with BuChE and IDO1 is increased, and a new idea is broadened for more efficient and targeted treatment of advanced AD diseases.
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Paragraph 0070-0072; 0082-0083
(2021/04/26)
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- Chiral Bidentate Phosphoramidite-Pd Catalyzed Asymmetric Decarboxylative Dipolar Cycloaddition for Multistereogenic Tetrahydrofurans with Cyclic N-Sulfonyl Ketimine Moieties
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An asymmetric [3 + 2] cycloaddition of vinyl ethylenecarbonates (VECs) and (E)-3-arylvinyl substituted benzo[d] isothiazole 1,1-dioxides has been developed using the Pd complex of a bidentate phosphoramidite (Me-BIPAM) as the catalyst, providing a wide variety of chiral multistereogenic vinyltetrahydrofurans in good yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, 99% ee).
- Lv, Hao-Peng,Yang, Xiao-Peng,Wang, Bai-Lin,Yang, Hao-Di,Wang, Xing-Wang,Wang, Zheng
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supporting information
p. 4715 - 4720
(2021/06/28)
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- Nucleus-independent chemical shift (NICS) as a criterion for the design of new antifungal benzofuranones
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The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p –1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 μg·mL–1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.
- González-Chávez, Marco Martín,González-Chávez, Rodolfo,Méndez, Francisco,Martínez, Roberto,Ni?o-Moreno, Perla Del Carmen,Ojeda-Fuentes, Luis Enrique,Richaud, Arlette,Zerme?o-Macías, María de los ángeles
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- Microwave-assisted synthesis and luminescent activity of imidazo[1,2-a]pyridine derivatives
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In this work, a series of phenacyl bromide derivatives was synthesized and employed as key intermediate for the synthesis of substituted imidazo[1,2-a]pyridines. First, phenacyl bromide molecules were obtained from the bromination reaction of acetophenones assisted by microwave irradiation, obtaining the products 4a-v in a 15 minutes reaction with yields in the range of 50% to 99%. Subsequently, the conjugation of these molecules with 2-aminopyridine conduced to the production of imidazo[1,2-a]pyridine derivatives (7a-v) in a 60-second reaction with yields of 24% to 99%. Improved yields were determined with respect to those obtained with more tedious methodologies like thermally and mechanically assisted routes. Intense luminescence emissions in the purple and blue regions of the electromagnetic spectra were observed under UV excitation according to the nature of the substituents. This environmentally friendly methodology is expected to constitute an important class of organic compounds for the development of biomarkers, photochemical sensors, and medicinal applications.
- Rodríguez, Juan C.,Maldonado, Rony A.,Ramírez-García, Gonzalo,Díaz Cervantes, Erik,de la Cruz, Fabiola N.
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p. 2279 - 2287
(2020/03/16)
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- Substituted 4-phenylthiazoles: Development of potent and selective A1, A3 and dual A1/A3 adenosine receptor antagonists
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Adenosine acts as a powerful signaling molecule via four distinct G protein-coupled receptors, designated A1, A2A, A2B and A3 adenosine receptors (ARs). A2A and A2B ARs are Gs-coupled, while A1 and A3 ARs inhibit cAMP production via Gi proteins. Antagonists for A1 and A3 ARs may be useful for the treatment of (neuro)inflammatory diseases including acute kidney injury and kidney failure, pulmonary diseases, and Alzheimer's disease. In the present study, we optimized the versatile 2-amino-4-phenylthiazole scaffold by introducing substituents at N2 and C5 to obtain A1 and A3 AR antagonists including dual-target compounds. Selective A1 antagonists with (sub)nanomolar potency were produced, e.g. 11 and 13. These compounds showed species differences being significantly more potent at the rat as compared to the human A1 AR, and were characterized as inverse agonists. Several potent and selective A3 AR antagonists, e.g. 7, 8, 17 and 22 (Ki values of 5–9 nM at the human A3 AR) were prepared, which were much less potent at the rat orthologue. Moreover, dual A1/A3 antagonists (10, 18) were developed showing Ki values between 8 and 42 nM. Docking and molecule dynamic simulation studies using the crystal structure of the A1 AR and a homology model of the A3 AR were performed to rationalize the observed structure-activity relationships.
- Abdelrahman, Aliaa,Yerande, Swapnil G.,Namasivayam, Vigneshwaran,Klapschinski, Tim A.,Alnouri, Mohamad Wessam,El-Tayeb, Ali,Müller, Christa E.
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supporting information
(2019/12/24)
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- Nickel-Catalyzed Asymmetric Addition of Aromatic Halides to Ketones: Highly Enantioselective Synthesis of Chiral 2,3-Dihydrobenzofurans Containing a Tertiary Alcohol
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A highly enantioselective and straightforward synthetic procedure to chiral 3-hydroxy-2,3-dihydrobenzofurans has been developed by nickel/bisoxazoline-catalyzed intramolecular asymmetric addition of aryl halides to unactivated ketones, giving 2,3-dihydrobenzofurans with a chiral tertiary alcohol at the C-3 position in good yields and excellent enantioselectivities (up to 92percent yield and 98percent ee). The gram-scale reaction also proceeded smoothly without a loss of yield and enantioselectivity.
- Li, Ying,Li, Wendian,Tian, Jiangyan,Huang, Guozheng,Lv, Hui
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supporting information
p. 5353 - 5357
(2020/07/14)
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- Aminoimidazole coupled pyridone derivatives serving as cystic fibrosis transmembrane conductance regulator inhibitors
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The invention relates to aminoimidazole coupled pyridone compounds and/or medicinal salt, a preparation method thereof as well as a medicine composition containing the compounds. The aminoimidazole coupled pyridone compounds can be used for treating and/or preventing cystic fibrosis (CF) related genetic diseases caused by cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation. The formula is shown in the description, wherein R is C3 or C4 or C5 or C6 or C7 or C8 naphthenic base, C3 or C4 or C5 or C6 or C7 or C8 aza-naphthenic base, C3 or C4 or C5 or C6 or C7 or C8 oxa-naphthenic base, morpholinyl, piperazinyl as well as piperazinyl with nitrogen substituted by straight chain or branched chain C1 or C2 or C3 or C4 or C5 alkyl.
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Paragraph 0026-0028
(2019/01/23)
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- Diaryl-containing imidazole compound and preparation method and medical application thereof
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The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).
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Paragraph 0057; 0058; 0059
(2019/02/21)
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- Organocatalytic Enantioselective Selenosulfonylation of a C-C Double Bond to Form Two Stereogenic Centers in an Aqueous Medium
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Organocatalytic selenosulfonylation of the C-C double bond of α,β-unsaturated ketones to construct two contiguous stereogenic centers in an aqueous medium was described. A series of α-selenyl and β-sulfonyl ketones with various functional groups were synthesized in good yields and enantioselectivities with saturated NaCl solution as the solvent. In addition, this protocol had been successfully scaled up to a decagram scale via a simple workup procedure.
- Chen, Zhili,Hu, Fangli,Huang, Shengli,Zhao, Zhengxing,Mao, Hui,Qin, Wenling
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p. 8100 - 8111
(2019/06/17)
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- Vinylethylene Carbonates as α,β-Unsaturated Aldehyde Surrogates for Regioselective [3 + 3] Cycloaddition
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Herein, we report a novel stepwise addition-controlled ring size method, to access tetrahydropyrimidines through an operationally simple [3 + 3] cycloaddition of vinylethylene carbonates with triazinanes. Interestingly, we could also use this method for a [3 + 3] oxidative cycloaddition, which allows the facile synthesis of polysubstituted terphenyls under mild conditions. Mechanistic studies suggest that vinylethylene carbonates could generate α,β-unsaturated aldehydes as 3-carbon synthons for cycloaddition via a combination process of Pd-catalyzed decarboxylation and β-H elimination.
- Xu, Yi,Chen, Lu,Yang, Yu-Wen,Zhang, Zhiqiang,Yang, Weibo
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supporting information
p. 6674 - 6678
(2019/09/03)
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- Novel arylimino thiazole compound, preparation method and uses thereof
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The present invention relates to a compound with antibacterial synergy activity, a preparation and uses thereof, particularly to a novel arylimino thiazole compound, a preparation method and uses thereof, and specifically discloses a class of compounds represented by a formula (I) or optical isomers, cis-trans isomers or pharmaceutically acceptable salts thereof, a preparation method and uses thereof. The invention further discloses a pharmaceutical composition containing the compound. The compound of the present invention can effectively enhance the antibacterial activity of antibiotics, andcan be used for treating antibiotic-resistant bacteria. The formula (I) is defined in the specification.
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Paragraph 0153; 0156; 0157; 0158; 0246; 0248; 0249; 0250
(2018/03/28)
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- Antibacterial synergist, preparation method and uses thereof
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The present invention relates to an antibacterial synergist, a preparation method and uses thereof, and specifically discloses a compound represented by a formula (I) and having antibacterial synergyactivity, or an optical isomer, a cis-trans isomer or a pharmaceutically acceptable salt thereof, and a preparation method thereof. The present invention further discloses a medical composition containing the compound, and uses thereof. According to the present invention, the compound can effectively enhance the antibacterial activity of polymyxin B against Acinetobacter baumannii and Klebsiella pneumoniae, and can be used for the antibacterial treatment of pathogenic bacteria insensitive to polymyxin or having low bacterial inhibition activity. The formula (I) is defined in the specification.
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Paragraph 0240; 0241; 0242; 0243; 0664; 0665; 0666-0668
(2018/03/28)
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- Divergent synthesis of N-heterocycles by Pd-catalyzed controllable cyclization of vinylethylene carbonates
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Here, we report a palladium-catalyzed controllable cyclization of vinyl ethylene carbonates that proceeds through formal migration [2+3] and [5+2] cycloadditions, respectively, under mild conditions. The transformation described here affords a series of synthetically versatile 5,7-membered N-heterocycles which are found in natural products and pharmaceuticals with biological and medicinal properties.
- Yang, Yuwen,Yang, Weibo
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supporting information
p. 12182 - 12185
(2018/11/21)
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- Substituted imidazole-1-vinyl compound and use thereof
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The invention relates to a substituted imidazole-1-ethylene compound as well as a preparation and an application thereof. The substituted imidazole-1-ethylene compound is a compound shown as a formula I, or salts thereof formed with medicinal acids or bases. According to the antifungal activity test performed on eight clinical fungi by the compound provided in the invention, a good fungus killing effect is achieved. The compound can serve as a novel broad-spectrum antifungal activity compound and is developed into antifungal medicines, disinfectants or feed additives.
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Paragraph 0051; 0228-0231
(2016/10/27)
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- A new kind of cystic fibrosis transmembrane conductance regulator factor inhibitors (by machine translation)
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The invention formula I indicated by the amidoimidazole coupling dihydro pyridine ketone compounds and/or their pharmaceutically acceptable salt and its preparation method, they can be used for treating and/or preventing the cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation in the factor of cystic fibrosis (CF) related hereditary diseases, and pharmaceutical compositions containing said compounds. wherein R1is at most is 3 halogen substituted phenyl, R2is( C1-C6)straight-chain or branched alkyl. (by machine translation)
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Paragraph 0022; 0023; 0024-0026
(2017/04/29)
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- FUSED IMIDAZOLE DERIVATIVES AS TGF-BETA INHIBITORS
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Disclosed are imidazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure Formula (I) and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein A, Z, X, R1, R2 m, p and a are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.
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Paragraph 0435
(2016/06/15)
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- Click chemistry inspired synthesis of piperazine-triazole derivatives and evaluation of their antimicrobial activities
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A series of novel piperazine-1,2,3-triazole derivatives, which entailed the bioisosteric replacement of the imidazole moiety and hybridization of two drug scaffolds was prepared by employing the regioselective copper (I)-catalysed azide-alkyne 1,3-dipolar cycloaddition reaction. The synthesized compounds were evaluated for antibacterial activities against Gram-negative (E. Coli and P. Putida), Gram-positive S. Aureus bacteria and fungicidal activities against F. oxysporum, F. gramillarium and F. monalliforme fungi. Compound 7ac′ exhibited moderate but promising antibacterial activity against Gram-negative bacteria and fungicidal activity against F. oxysporum and F. gramillarium.
- Khedar, Poonam,Pericherla, Kasiviswanadharaju,Singh, Rajnish Prakash,Jha, Prabhat Nath,Kumar, Anil
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p. 3117 - 3126
(2016/02/10)
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- De novo design of non-coordinating indolones as potential inhibitors for lanosterol 14-α-demethylase (CYP51)
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The development of antifungal drugs that inhibit lanosterol 14-α-demethylase (CYP51) via non-covalent ligand interactions is a strategy that is gaining importance. A series of novel tetraindol-4-one derivatives with 1- and 2-(2,4-substituted phenyl) side chains were designed and synthesized based on the structure of CYP51 and fluconazole. The antifungal activities of these derivatives against eight human pathogenic filamentous fungi and yeast strains were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds 8a-g displayed activity against Candida tropicalis, Candida guilliermondii and Candida parapsilosis with a minimum inhibitory concentration (MIC) value until 8 μg mL-1, on the other hand compounds 7a-g showed activity against Aspergillus fumigatus with a MIC value of 31.25 μg mL-1. A molecular modeling study of the binding interactions between compounds 6, 7d, 8g and the active site of MtCYP51 was conducted based on the computational docking results.
- Gonzalez-Chavez, Rodolfo,Martinez, Roberto,Torre-Bouscoulet, Maria Eugenia,Gallo, Marco,Gonzalez-Chavez, Marco Martin
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- ARYLSUBSTITUTED THIAZOLOTRIAZOLES AND THIAZOLOIMIDAZOLES
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This disclosure relates to compounds, compositions and methods for the treatment of various disorders. In particular, the disclosure relates to thiazolotriazole and thiazoloimidazole compounds which agonize the activity of the protein TGR5. Formula (I)
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Page/Page column 40
(2013/04/13)
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- SAR, cardiac myocytes protection activity and 3D-QSAR studies of salubrinal and its potent derivatives
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Salubrinal is a selective inhibitor of endoplasmic reticulum (ER) stress and affords remarkable protection to cardiomyocytes. By studying the structure-activity relationship (SAR) of salubrinal, it was found that modification of the quinoline ring terminus and thiourea unit could confer the compound PP1-24 with markedly enhanced cardioprotective activity (EC 50 2 = 0.741, r2 = 0.991).
- Liu,He,Li,Li,Liu,Zhong,Li
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p. 6072 - 6079
(2013/02/22)
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- Click chemistry inspired structural modification of azole antifungal agents to synthesize novel 'drug like' molecules
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A new class of 'drug like' 1,4-disubstituted-1,2,3-triazoles is synthesized using one-pot reaction of sodium azide, α-bromo ketones, and alkynes in PEG-400/water (1:1, v/v) under the click chemistry reaction condition followed by reduction of keto group and alkylation. The method is simple, efficient and gives good yield of novel 1,2,3-triazole derivatives.
- Pericherla, Kasiviswanadharaju,Khedar, Poonam,Khungar, Bharti,Kumar, Anil
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supporting information
p. 6761 - 6764
(2013/01/15)
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- Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors
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The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds.
- Chimenti, Franco,Secci, Daniela,Bolasco, Adriana,Chimenti, Paola,Granese, Arianna,Carradori, Simone,MacCioni, Elias,Cardia, M. Cristina,Yanez, Matilde,Orallo, Francisco,Alcaro, Stefano,Ortuso, Francesco,Cirilli, Roberto,Ferretti, Rosella,Distinto, Simona,Kirchmair, Johannes,Langer, Thierry
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experimental part
p. 5063 - 5070
(2010/09/08)
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- ANTIFUNGAL 1, 2, 4-TRIAZOLYL DERIVATIVES
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The present invention relates to novel triazole compounds of the formulae (I), ( II ) and ( IV) as defined below, to agricultural and pharmaceutical compositions containing them and to their use as fungicides, antimycotic, anticancer and antiviral agents.
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Page/Page column 257
(2011/01/12)
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- Enzyme-catalysed approach to the preparation of triazole antifungals: synthesis of (-)-genaconazole
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The work describes a new enzyme-mediated approach to optically active epoxide (2R,3S)-6, which is an important key intermediate in the preparation of single enantiomers of chiral azole antifungals. The conversion of (2R,3S)-6 into (-)-genaconazole is reported as an example of its synthetic relevance.
- Acetti, Daniela,Brenna, Elisabetta,Fuganti, Claudio,Gatti, Francesco G.,Serra, Stefano
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experimental part
p. 2413 - 2420
(2010/03/24)
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- Synthesis and biological evaluation of imidazol-2-one derivatives as potential antitumor agents
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A new series of aryl substituted imidazol-2-one derivatives structurally related to combretastatin A-4 (CA-4) were synthesized and evaluated for their cytotoxic activities in vitro against various human cancer cell lines including MDR cell line. The cytotoxic effects of compounds 7b and 7i proved to be similar to or greater than that of docetaxel. The highly active compound 7b also exhibited excellent inhibitory activity on tumor growth in vivo.
- Xue, Na,Yang, Xiaochun,Wu, Rui,Chen, Jing,He, Qiaojun,Yang, Bo,Lu, Xiuyang,Hu, Yongzhou
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p. 2550 - 2557
(2008/09/21)
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- IRIDIUM COMPLEX COMPOUND, ORGANIC ELECTROLUMINESCENT DEVICE OBTAINED BY USING THE SAME, AND USES OF THE DEVICE
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The present invention provides an organic EL device having a high luminous efficiency and a long life, and an iridium complex compound used for preparing the above device. The iridium complex compound is represented by the following Formula (1): (1) [in Formula (1), R1 to R4 are each independently a specific group; at least one of R1 to R4 is a group having 2 or more carbon atoms; R5 to R8 are each independently a specific group; and at least one of R5 to R8 is a specific electron-withdrawing group; (with the proviso that R1 to R8 are not combined with each other to form rings)].
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Page/Page column 60-61
(2008/12/05)
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- METAL COMPLEX COMPOUND AND ORGANIC ELECTROLUMINESCENT DEVICE USING SAME
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A metal complex compound having a special structure containing metals such as iridium. An organic electroluminescence device which comprises at least one organic thin film layer sandwiched between a pair of electrode consisting of an anode and a cathode, wherein the organic thin film layer comprises the above metal complex compound, which emits light by applying an electric voltage between the pair of electrode. An organic EL device employing the novel metal complex compound emits various phosphorous lights including blue light having an enhanced current efficiency and prolonged lifetime.
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Page/Page column 371-372
(2010/11/08)
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- SUBSTITUTED THIAZOLE DERIVATIVES BEARING 3-PYRIDYL GROUPS, PROCESS FOR PREPARING THE SAME AND USE THEREOF
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The present invention provides a pharmaceutical composition having a steroid C17,20-lyase inhibitory activity, which is useful as a prophylactic or therapeutic agent of prostatism, tumor such as breast cancer and the like, more particularly, a steroid C17,20-lyase inhibitor containing a compound represented by the formula: wherein A1 is an aromatic hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, one of A2 and A3 is a hydrogen atom, a halogen atom, a C1-4 aliphatic hydrocarbon group optionally having substituents or an optionally esterified carboxyl group, the other of A2 and A3 is an aromatic hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, and at least one of A1, A2 and A3 is a 3-pyridyl group optionally having substituents, or a salt thereof or a prodrug thereof.
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Page/Page column 35
(2008/06/13)
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- MONOCYCLIC AROYLPYRIDINONES AS ANTIINFLAMMATORY AGENTS
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The present invention relates to monocyclic aroylpyridinones, processes for their preparation, and their use in medicaments, especially for the treatment of COPD: (formula I).
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Page/Page column 71-72
(2010/02/07)
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- Pyrrole derivatives and medicinal composition
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The invention relates to a pharmaceutical composition comprising a pyrrole derivative of the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate of either of them, as an active ingredient. STR1 (wherein R1 represents hydrogen or alkoxycar91 bonylamino, R2 represents alkyl, aryl which may be substituted, aromatic heterocyclyl which may be substituted, unsubstituted amino, monoalkylamino, dialkylamino, or cyclic amino which may be substituted; R3 represents cyano or carbamoyl; R4 represents hydrogen or alkyl; E represents alkylene; q is equal to 0 or 1, A represents methyl, aryl which may be substituted, or aromatic heterocyclyl which may be substituted). The pharmaceutical composition of the invention is effective for the treatment of pollakiuria or urinary incontinence.
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- Process for producing optically active carbinols
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The present invention relates to a process for producing optically active halomethyl phenyl carbinols of the formula (1), comprising reducing halomethyl phenyl ketones of the formula (2) using an asymmetric reducing agent obtained from boranes and optically active α-phenyl-substituted-β-amino alcohols of the formula (3) or optically active α-non-substituted-β-amino alcohols of the formula (4). The present invention further relates to a process for producing optically active carbinols, comprising reacting a prochiral keytone with an asymmetric reducing agent obtained from optically active β-amino alcohols of the formula (5), a metal boron hydride and Lewis acid or lower dialkyl sulfuric acid. All of the formulas (1) to (5) are the same as shown in the specification.
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- Aldol condensation of Evans chiral enolates with acetophenones. Its application to the stereoselective synthesis of homochiral antifungal agents
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The results of the aldol condensation of Evans chiral imide enolates with a series of acetophenones are reported. Activated acetophenones, such as 2,4-difluoroacetophenone, α-chloroacetophenone, and α-chloro- and α-bromo-2,4-difluoroacetophenone, reacted with the lithium enolate of 5 with good levels of enolate facial diastereoselectivity toward the (2R)-isomers (> 10:1) but with low anti: syn selectivity (ca. 3:2). Sodium and potassium enolates of 5 were also tested. The nature of the solvent influenced the degree of diastereofacial biases. Less activated ketones, such as acetophenone, reacted only to a ca. 50% extent without facial or anti:syn stereoselectivities. Chairlike pericyclic transition states are believed to govern the reaction. When α-bromoacetophenones were used, longer reaction times and higher temperatures resulted in the selective formation of the S2 epoxide (syn(2R,3R), 11) with good levels of selectivity. Equilibration studies performed in THF with the corresponding metal aldolates generated in situ by deprotonation of the aldol adducts indicated that an aldol/retroaldol process was first established followed by a slower formation of the epoxide. Stereoselection is thought to originate by a faster oxirane formation of the syn bromohydrins as compared to the anti due to steric interactions between the α-group and the leaving bromide. Optimum retroaldol-epoxide formation rates were obtained using the sodium enolate in ether at -78°C. Under these conditions the S1:S2:A1:A2 ratio of epoxides was 6:83:10:0.3 and the major isomer was isolated by recrystallization in 79% yield. An improved synthesis of amino alcohol 3, an advanced intermediate in the preparation of orally active antifungal agents, using a tandem of this new ketone-aldol technology and a Curtius rearrangement, is reported. The new sequence proceeds with an overall yield of 53% and does not require chromatographic purifications.
- Bartroli,Turmo,Belloc,Forn
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p. 3000 - 3012
(2007/10/02)
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