- Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83
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We have developed a new series of simple biaryl piperidine derivatives (11–19) based on biaryl naphthylisoquinoline alkaloid Ealamine-A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5′-fluoro-2′-methoxyphenyl derivative 14 and 3′,5′-difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 μM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12, 15, and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.
- Rathnakar, Bethi,Sinha, Kislay Kumar,Prasad, Surendra Rajit,Khan, Mohd. Imran,Narsaiah, Chelimela,Rameshwar, Nimma,Satyanarayana, Mavurapu
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- TGF-betaR1 inhibitor and application thereof
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The invention belongs to the field of medical chemistry, and particularly relates to a compound serving as a TGF-betaR1 inhibitor and application of the compound. Specifically, the invention providesa compound shown as a formula I or an isomer, a pharmaceutically acceptable salt, a solvate, a crystal or a prodrug thereof, a preparation method of the compounds, a pharmaceutical composition containing the compounds and application of the compounds or the composition to treatment and/or prevention of TGF-betaR1 related diseases, such as cancers, tissue hyperplasia diseases, fibrosis and inflammatory diseases. The compound provided by the invention shows significant inhibitory activity on TGF-betaR1 kinase, and is very expected to become a therapeutic agent for TGF-betaR1 related diseases.
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Paragraph 0441-0442; 0443-0445; 0525; 0527-0529
(2020/06/09)
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- Copper-Catalyzed Modular Amino Oxygenation of Alkenes: Access to Diverse 1,2-Amino Oxygen-Containing Skeletons
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Copper-catalyzed alkene amino oxygenation reactions using O-acylhydroxylamines have been achieved for a rapid and modular access to diverse 1,2-amino oxygen-containing molecules. This transformation is applicable to the use of alcohols, carbonyls, oximes, and thio-carboxylic acids as nucleophiles on both terminal and internal alkenes. Mild reaction conditions tolerate a wide range of functional groups, including ether, ester, amide, carbamate, and halide. The reaction protocol allows for starting with free amines as the precursor of O-benzoylhydroxylamines to eliminate their isolation and purification, contributing to broader synthetic utilities. Mechanistic investigations reveal the amino oxygenation reactions may involve distinct pathways, depending on different oxygen nucleophiles.
- Hemric, Brett N.,Chen, Andy W.,Wang, Qiu
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supporting information
p. 1468 - 1488
(2019/01/25)
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- CARBOXYLIC ACID AROMATIC 1,2-CYCLOPROPYLAMIDES
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The present invention relates to carboxylic acid aromatic 1,2-cyclopropylamides of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.
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Paragraph 0783-0785
(2019/06/20)
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- AMINE-SUBSTITUTED HETEROCYCLIC COMPOUNDS AS EHMT2 INHIBITORS AND DERIVATIVES THEREOF
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The present disclosure relates to amine-substituted heterocyclic compounds and derivatives thereof. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating a disorder (e.g., cancer) by administering an amine-substituted heterocyclic heterocyclic compound disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.
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Paragraph 0515
(2019/05/10)
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- CARBOXYLIC ACID AROMATIC AMIDES AS ANTAGONISTS OF BRADYKININ B1 RECEPTOR
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The present invention relates to carboxylic acid aromatic amides compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing
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Page/Page column 133
(2018/07/29)
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- Pd-Catalyzed/Iodide-Promoted α-Arylation of Ketones for the Regioselective Synthesis of Isocoumarins
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A variety of isocoumarins have been synthesized directly from 2-halobenzoates and ketones through a palladium-catalyzed α-arylation step followed by an intramolecular cyclization process. The addition of iodide anions to the reaction mixture increased yields and selectivities especially when 2-bromobenzoates were employed. This phosphine-free one-pot synthesis features a high functional group tolerance and gives access to richly decorated isocoumarins. This general methodology was successful in the total synthesis of Xyridin A, an important natural product with antibacterial and antifungal activity.
- Casnati, Alessandra,Maggi, Raimondo,Maestri, Giovanni,Della Ca, Nicola,Motti, Elena
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p. 8296 - 8303
(2017/08/14)
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- HETEROCYCLIC COMPOUND
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The present invention provides a heterocyclic compound having a CDK8 and/or CDK19 inhibitory effect. The present invention provides a compound represented by formula (I) (in the formula, the symbols are as defined in the description) or a salt thereof.
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Paragraph 0564; 0778; 0779
(2017/04/11)
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- Heterocyclic compound
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本發明提供一種具有CDK8/19抑制活性之雜環化合物。本發明提供一種如下式代表之化合物(其中各代號均如本文之定義)或其鹽。 The present invention provides a heterocyclic compound possessing CDK8/19 inhibitory activity. The present invention provides a compound represented by the formula wherein each symbol is as defined herein, or a salt thereof.
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Paragraph 0238
(2017/09/28)
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- Production method for 3, 3-dimethyl-3, 4-dihydro-1h-quinoxaline-2-one derivative and intermediate for said production method
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To provide: a novel production method suitable for industrial production of a 3, 3-dimethyl-3, 4-dihydro-1H-quinoxaline-2-one derivative; and a synthetic intermediate therefor. Provided is a production method is for a compound indicated by formula (1) or a salt thereof, said production method including: a step in which a compound indicated by formula (2) or a salt thereof is reacted with a nitrating agent and a compound indicated by formula (3) or a salt thereof is obtained; and a step in which the compound indicated by formula (3) or a salt thereof is reduced and a compound indicated by formula (1) or a salt thereof is obtained. (Each symbol in the formulas (1, 2, 3) is the same as in the definitions in claim 1.)
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Paragraph 0226; 0227-0228
(2017/03/08)
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- PRODUCTION METHOD FOR 3,3-DIMETHYL-3,4-DIHYDRO-1H-QUINOXALIN-2-ONE DERIVATIVE AND INTERMEDIATE FOR SAID PRODUCTION METHOD
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An object is to provide a novel production method suitable for industrial production of a 3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one derivative and a synthetic intermediate for the method. Provided is a method for producing a compound represented by formula (1): wherein R1 represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aryl group, R2 represents a hydrogen atom, an optionally substituted alkyl group, a hydroxy group, or nitrogen atom-protecting group, R3 represents a hydrogen atom, an optionally substituted alkyl group, a hydroxy group, or a nitrogen atom-protecting group, and X represents a hydroxy group or a leaving group, or a salt thereof, the method comprising the steps of: reacting a compound represented by formula (2): wherein R1, R2, and X are the same as defined in formula (1), R4 represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aryl group, or a salt thereof with a nitrating agent to obtain a compound represented by formula (3) wherein R1, R2, R4, and X are the same as defined in formulae (1) and (2), or a salt thereof, and reducing the compound represented by formula (3) or the salt thereof to obtain the compound represented by formula (1) or the salt thereof.
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Paragraph 0128-0129
(2016/08/17)
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- METHODS AND COMPOSITIONS FOR INHIBITION OF BROMODOMAIN AND EXTRATERMINAL PROTEINS
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The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using
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Page/Page column 53
(2016/06/13)
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- Development of a practical synthesis of 7-bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1hquinoxalin- 2-one
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Synthesis of 7-bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro- 1H-quinoxalin-2-one from 5-amino-2-bromobenzoic acid was achieved in an overall yield of 27% over four steps. This is a significant improvement from the previous six-step process, which affo
- Kudo, Kazuhiro,Honda, Takahiro,Yamamoto, Noriyoshi
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p. 1591 - 1602
(2015/09/28)
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- Donor-acceptor biaryl lactones: PH induced molecular switches with intramolecular charge transfer modulation
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The physical properties of biaryl-containing compounds are known to be highly dependent on molecular geometry. We report the syntheses and fundamental spectroscopic study of two donor-acceptor biaryl lactone (6H-benzo[c]chromen-6- one) pH-driven switches.
- Carlson, Erik J.,Riel, Asia Marie S.,Dahl, Bart J.
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supporting information
p. 6245 - 6249,5
(2012/12/11)
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- GLUCOCORTICOID RECEPTOR AGONIST COMPRISING NOVEL 1,2,3,4-TETRAHYDROQUINOXALINE DERIVATIVE CONTAINING PHENYL GROUP HAVING SULFONIC ACID ESTER STRUCTURE INTRODUCED THEREIN AS SUBSTITUENT
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The object aims to find a novel pharmacological activity of a novel 1,2,3,4-tetrahydroquinoxaline derivative which contains, as a substituent, a phenyl group having a sulfonic acid ester structure introduced therein. A compound represented by general formula (1) or a salt thereof is useful as a glucocorticoid receptor agonist, particularly as a therapeutic agent for diseases against which a glucocorticoid receptor agonist (e.g., a steroid) is believed to be effective, such as inflammatory bone/joint diseases, inflammatory ophthalmic diseases (inflammatory ophthalmic diseases in the anterior or posterior segment of an eye). R1 represents a group represented by general formula (2a), (3a), (4a) or (5a); R2 represents a lower alkyl group which may have a substituent, a lower cycloalkyl group which may have a substituent, or the like; R3 represents a lower alkyl group; R4, R5, R6 or R7 represent a halogen atom, a lower alkyl group which may have a substituent, a hydroxy group, a lower alkoxy group which may have a substituent, or the like; and m, n, p or q represents a number of 0, 1 or 2.
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Page/Page column 17-18
(2011/06/23)
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- HETEROCYCLIC ANTIVIRAL COMPOUNDS
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Compounds having the formula I wherein wherein R1, R2, R3b, R4a, R4b, R4c and as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods
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Page/Page column 20
(2010/12/29)
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- NOVEL 1,2,3,4-TETRAHYDROQUINOXALINE DERIVATIVE WHICH HAS, AS SUBSTITUENT, PHENYL GROUP HAVING SULFONIC ACID ESTER STRUCTURE OR SULFONIC ACID AMIDE STRUCTURE INTRODUCED THEREIN AND HAS GLUCOCORTICOID RECEPTOR-BINDING ACTIVITY
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The compounds represented in general formula (1) or a salt thereof are useful for glucocorticoid receptor modulators. In the formula, R1 represents a lower alkyl group, a lower cycloalkyl group, an aryl group and the like; R2 represents a hydrogen atom, a lower alkyl group and the like; R3 represents a hydrogen atom, a lower alkyl group and the like; R4 and R5 represent a hydrogen atom, a lower alkyl group and the like; R6 represents a hydrogen atom, a lower alkyl group and the like; R7 represents a hydrogen atom, a lower alkyl group, a lower alkenyl group and the like; W represents an oxygen atom, a sulfur atom, NR8 and the like; R8 represents a hydrogen atom, a lower alkyl group and the like; X represents an oxygen atom or a sulfur atom; Y represents a lower alkylene group and the like; Z represents an oxygen atom, a sulfur atom, NR9, OCO or OSO2; R9 represents a hydrogen atom, a lower alkyl group and the like respectively.
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Page/Page column 17
(2010/03/02)
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- Electrophilic bromination of meta-substituted anilines with N-bromosuccinimide: Regioselectivity and solvent effect
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N-Bromosuccinimide-mediated electrophilic aromatic bromination of a series of anilines substituted with an electron-with-drawing group in the meta position was investigated. The regioselectivity of the reaction is markedly dependent on the polarity of the solvent and the bromination reaction can be tuned by appropriate selection of the reaction medium. Georg Thieme Verlag Stuttgart.
- Bartoli, Sandra,Cipollone, Amalia,Squarcia, Antonella,Madami, Andrea,Fattori, Daniela
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experimental part
p. 1305 - 1308
(2009/12/24)
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- 2-ARYL- AND 2-HETEROARYLTHIAZOLYL COMPOUNDS, METHODS FOR THEIR PREPARATION AND USE THEREOF
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The present invention discloses fused bicyclic 2-aryl- or 2-heteroarylthiazolyl compounds and their pharmaceutically acceptable salts and esters thereof, which are useful for inhibiting the growth of cancerous cells, inhibiting human breast carcinoma tumo
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Page/Page column 76; 77
(2009/10/22)
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- 2-ARYL- AND 2-HETEROARYLTHIAZOLYL COMPOUNDS, METHODS FOR THEIR PREPARATION AND USE THEREOF
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The present invention discloses fused heterobicyclic 2-aryl- and 2-heteroarylthiazolyl compounds and their pharmaceutically acceptable salts and esters thereof, which are useful for inhibiting the growth of cancerous cells, inhibiting human breast carcino
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Page/Page column 41
(2009/10/22)
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- NOVEL 1,2,3,4-TETRAHYDROQUINOXALINE DERIVATIVE HAVING GLUCOCORTICOID RECEPTOR BINDING ACTIVITY
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An object of the present invention is to synthesize a novel 1,2,3,4-tetrahydroquinoxaline derivative represented by formula (1) and to find a pharmacological action of the derivative. In the formula, the R1 represents a halogen, an alkyl, cycloalkyl, aryl or heterocyclic group, or the like; p represents 0 to 5; R2 represents a halogen, an alkyl, hydroxyl or alkoxy group, or the like; q represents 0 to 2; R3 represents hydrogen, an alkyl, alkenyl, alkylcarbonyl or arylcarbonyl group, or the like; R4 and R5 independently represent hydrogen, a halogen, an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclic group, or the like; R6 represents hydrogen, an alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclic group, or the like; A represents an alkylene; R7 represents OR8, NR8R9, SR8, S(O)R8, S(O)2R8; and X represents O or S.
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Page/Page column 33
(2009/01/20)
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- SELECTIVE ANDROGEN RECEPTOR MODULATORS
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A compound of formula (I) or an isomer, metabolite, or a pharmaceutically acceptable salt or ester thereof is disclosed. The compound of the invention possesses utility as a tissue-selective androgen receptor modulator (SARM) and is useful in hormonal the
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Page/Page column 9-10
(2008/06/13)
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- Compounds, Compositions and Methods
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Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.
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Page/Page column 18
(2010/11/28)
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- Benzothiazole protein trosine kinase inhibitors
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Novel benzothiazoles and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic disorders.
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