- Aminobenzoic acid derivatives as antioxidants and cholinesterase inhibitors; synthesis, biological evaluation and molecular docking studies
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Cholinesterase namely, acetyl- and butyrylcholinesterase (AChE and BChE, respectively), has been recognized as a primary class of enzyme that hydrolyzes the acetylcholine (ACh) neurotransmitter in synaptic junctions. Diminished levels of the neurotransmitter in synaptic junction lead to Alzheimerís disease (AD). Inhibition of cholinesterase is thus, an attractive strategy for AD treatment. The study includes the synthesis and characterization of a series of 2-, 3- and 4-aminobenzoic acid derivatives (1a?5c), their biological screening against cholinesterase enzyme and molecular docking study to demonstrate putative binding modes. Antioxidant potential of the synthesized series was also determined. The cholinesterase enzyme inhibition assay showed that compound 5b has the highest inhibition potential against acetylcholinesterase with an IC50 value of 1.66 ± 0.03 μM while in case of butyrylcholinesterase, compound 2c has the highest inhibitory potential with an IC50 value of 2.67 ± 0.05 μM. Molecular docking studies supports the results of enzyme inhibition potential with binding energy value ?G = -9.54 Kcal mol-1 for compound 5b in case for acetylcholinesterase while for butyrylcholinesterase, ?G = -5.53 Kcal mol-1 was obtained for compound 2c. The synthesized series of compounds also shows mild to moderate antioxidant potential. The benzoyl- containing compounds shows better antioxidant activity as compared to other derivatives of the synthesized series. Based on the molecular docking studies and enzyme inhibition potential, the synthesized series of compounds can be regarded as potent cholinesterase inhibitors and can be used for designing and synthesizing more potent drugs for Alzheimerís disease and neurodegenerative diseases.
- Iftikhar, Kiran,Murtaza, Shahzad,Kousar, Naghmana,Abbas, Aadil,Tahir, Muhammad Nawaz
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p. 385 - 396
(2018/04/23)
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- Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis
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Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (1 and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.
- Heimburg, Tino,Chakrabarti, Alokta,Lancelot, Julien,Marek, Martin,Melesina, Jelena,Hauser, Alexander-Thomas,Shaik, Tajith B.,Duclaud, Sylvie,Robaa, Dina,Erdmann, Frank,Schmidt, Matthias,Romier, Christophe,Pierce, Raymond J.,Jung, Manfred,Sippl, Wolfgang
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supporting information
p. 2423 - 2435
(2016/04/10)
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- Design and synthesis of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors
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Monoamine oxidase-B (MAO-B) inhibitor has been used as neuroprotectants to treat the motor deficits of Parkinson's disease (PD). We designed and synthesized a class of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors. The compounds have various inhibitory effects, with compound 6a having a Ki value of 0.26 lM. Their promising activity in vitro suggests potential use in the treatment of PD.
- Song, Bo,Xiao, Tong,Qi, Xiaolu,Li, Ling-Na,Qin, Kuiyou,Nian, Siyun,Hu, Guo-Xin,Yu, Yinfei,Liang, Guang,Ye, Faqing
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experimental part
p. 1739 - 1742
(2012/04/04)
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- Structure-based redesign of an edema toxin inhibitor
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Edema factor (EF) toxin of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3′,5′-cyclic adenosine mo
- Chen, Deliang,Ma, Lili,Kanalas, John J.,Gao, Jian,Pawlik, Jennifer,Jimenez, Maria Estrella,Walter, Mary A.,Peterson, Johnny W.,Gilbertson, Scott R.,Schein, Catherine H.
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experimental part
p. 368 - 376
(2012/03/22)
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- PHARMACEUTICAL COMPOSITION FOR INHIBITING THE TRANSCRIPTION FACTOR INDUCIBLE BY HYPOXIA, MODULATORS OF PATHOLOGICAL PROCESSES OF ANGIOGENESIS, ONCOGENESIS, INFLAMMATION, APOPTOSIS, AND CELLULAR THERAPY
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The present invention is included in the field of pharmacology and medical chemistry and relates to novel molecules represented by general formula (I), especially the one called FM19G11, as well as to pharmaceutical compositions containing them. Said pharmacologically optimized compositions are capable of modulating and/or inhibiting the transcription of genes modulated by the hypoxia-inducible transcription factor (HIF) and which are directly and/or indirectly involved in pathological processes related to cancer, inflammation, tissue repair, stem cell differentiation and regenerative therapy. The present invention also relates to a method for the synthesis of said molecules (I) and to the use thereof in the manufacture of a medicament for the treatment of the mentioned pathological processes.
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Page/Page column 21
(2011/04/18)
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- COMPOSITION FOR PREVENTING HARMFUL ORGANISMS
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There is a harmful organism that cannot be controlled or is difficult to be controlled with the use of a single agent of a compound represented by the general formula (1) according to the invention, an insecticide, a miticide or a fungicide. Accordingly, an object of the invention is to provide a composition for preventing harmful organisms for efficiently controlling such a harmful organism. That is, the invention is directed to a composition for preventing harmful organisms, characterized by comprising the compound represented by the general formula (1) and other insecticides, miticides or fungicides as active ingredients, wherein, in the formula, A1, A2, A3 and A4 independently represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom, G1 and G2 independently represent an oxygen atom or a sulfur atom; R1 and R2 independently represent a hydrogen atom or a C1 to C4 alkyl group; Xs may be the same or different and represent a hydrogen atom, a halogen atom or a trifluoromethyl group; Q1 represents a substituent such as a phenyl group or a heterocyclic group; and Q2 represents a substituent such as a phenyl group or a heterocyclic group.)
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Page/Page column 97-98
(2009/07/10)
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- PEST CONTROL COMPOSITION
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There is a harmful organism that cannot be controlled or is difficult to be controlled with the use of a single agent of a compound represented by the general formula (1) according to the invention, an insecticide, a miticide or a bactericide. Accordingly, an object of the invention is to provide a composition for preventing harmful organisms for efficiently controlling such a harmful organism. That is, the invention is directed to a composition for preventing harmful organisms, characterized by comprising the compound represented by the general formula (1) and other insecticides, miticides or bactericides as active ingredients, wherein, in the formula, A1, A2, A3 and A4 independently represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom; G1 and G2 independently represent an oxygen atom or a sulfur atom; R1 and R2 independently represent a hydrogen atom or a C1 to C4 alkyl group; Xs may be the same or different and represent a hydrogen atom, a halogen atom or a trifluoromethyl group; Q1 represents a substituent such as a phenyl group or a heterocyclic group; and Q2 represents a substituent such as a phenyl group or a heterocyclic group.)
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Page/Page column 145
(2008/06/13)
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- INSECTICIDAL AND BACTERICIDAL COMPOSITION
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An insecticidal and fungicidal composition capable of controlling crop diseases and insect pests at the same time by combining an insecticidal active ingredient and a fungicidal active ingredient is provided. The insecticidal and fungicidal composition is
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Page/Page column 143
(2008/12/06)
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- Brine-mediated efficient benzoylation of primary amines and amino acids
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Benzoylation of primary amines and amino acids is efficiently carried out in a brine solution using a stoichiometric amount of benzoyl chloride followed by trituration with aqueous saturated bicarbonate solution. Copyright Taylor & Francis Group, LLC.
- Chattopadhyay, Gautam,Chakraborty, Suchandra,Saha, Chandan
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experimental part
p. 4068 - 4075
(2009/04/11)
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- AMIDE DERIVATIVE AND PESTICIDE CONTAINING SUCH COMPOUND
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Disclosed is a compound having high pesticidal effects which is represented by the general formula (1) below. Also disclosed is a pesticide containing such a compound as an active ingredient. (1) (In the formula, A1, A2, A3 and A4 respectively represent a carbon atom or the like; R1 and R2 respectively represents a hydrogen atom or the like; G1 and G2 respectively represents an oxygen atom or the like; X represents a hydrogen atom, a halogen atom or the like; n represents an integer of 0-4; Q1 represents a substituted phenyl group, a substituted heterocyclic group or the like; and Q2 represents a substituted phenyl group, a substituted heterocyclic group or the like.)
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Page/Page column 177
(2008/06/13)
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- AMIDE DERIVATIVES, PROCESS FOR PRODUCTION OF THE SAME, AND METHOD FOR APPLICATION THEREOF AS INSECTICIDE
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An object of the present invention is to provide a compound represented by Formula (1): wherein A1, A2, A3 and A4 each represent a carbon atom, a nitrogen atom or an oxidized nitrogen atom; R1 and R2 each represent a hydrogen atom, an optionally substituted alkyl group or an optionally substituted C1-C4 alkylcarbonyl group; G1 and G2 each represent an oxygen atom or a sulfur atom; X, which may be identical or different each other, represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a trifluoromethyl group; n is an integer of 0 to 4; and Q1 represents an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted heterocyclic group; Q2 represents a phenyl group or heterocyclic group having one or more substituents, at least one of the substituent being any of a C1-C4 haloalkoxy group, a C2-C6 perfluoroalkyl group, a C1-C6 perfluoroalkylthio group, a C1-C6 perfluoroalkylsulfinyl group and a C1-C6 perfluoroalkylsulfonyl group, an insecticide comprising the compound as the active ingredient, and a process for preparation thereof.
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Page/Page column 168
(2010/11/24)
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- AMIDE DERIVATIVE, PESTICIDE CONTAINING SUCH COMPOUND AND USE THEREOF
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Disclosed are a compound represented by the general formula (1) below which exhibits a high insecticidal effect, and a pesticide containing such a compound as an active ingredient. (1) (In the formula, A1, A2, A3 and A4 respectively represent a carbon atom or the like; R1 and R2 respectively represent a hydrogen atom, an alkyl group or the like; G1 and G2 respectively represent an oxygen atom or the like; X represents a hydrogen atom, a halogen atom or the like; n represents an integer of 0-4; Q1 represents a substituted phenyl group, a substituted heterocyclic group or the like; and Q2 represents a phenyl group having a haloalkylthio group or the like, a heterocyclic group or the like.)
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Page/Page column 133
(2008/06/13)
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- A consideration of various ionic forms of amino acids in evaluating the rate constant of N-acylation
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The concentrations of ionic forms of p- and m-aminobenzoic acids in water and water-dioxane solvents of variable composition were calculated at various pH values. Based on the results of the calculations and on the kinetic data obtained previously, the ra
- Kuritsyn,Kalinina
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p. 2004 - 2006
(2007/10/03)
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- KINETICS OF ACYLATION OF ANILINES MONOSUBSTITUTED IN THE RING BY BENZOYL CHLORIDE IN N,N-DIMETHYLACETAMIDE
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The kinetics of the acylation of meta- and para-substituted primary arylamines by benzoyl chloride in N,N-dimethylacetamide was studied.The sensitivity of the reaction to changes in the structure of the arylamine in N,N-dimethylacetamide is lower than in other organic solvents.A mechanism involving catalysis of the acylation reaction by the solvent molecules is proposed.
- Kuz'min, N. I.,Kabanova, N. I.,Zhizdyuk, B. I.,Chegolya, A. S.
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p. 2139 - 2141
(2007/10/02)
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