1760-84-5Relevant academic research and scientific papers
COMPOUNDS AND USES THEREOF
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Page/Page column 65, (2021/03/19)
The present invention relates to compositions and methods for the treatment of HA01 -associated disorders, such as primary hyperoxaluria 1.
Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors
Sharma, Horrick,Patil, Shivaputra,Sanchez, Tino W.,Neamati, Nouri,Schinazi, Raymond F.,Buolamwini, John K.
experimental part, p. 2030 - 2045 (2011/05/05)
HIV-1 integrase is one of the three most important enzymes required for viral replication and is therefore an attractive target for anti retroviral therapy. We herein report the design and synthesis of 3-keto salicylic acid chalcone derivatives as novel HIV-1 integrase inhibitors. The most active compound, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl]benzoic acid (25) was selectively active against integrase strand transfer, with an IC 50 of 3.7 μM. While most of the compounds exhibited strand transfer selectivity, a few were nonselective, such as 5-bromo-3-[3-(4- bromophenyl)acryloyl]-2-hydroxybenzoic acid (15), which was active against both 3′-processing and strand transfer with IC50 values of 11 ± 4 and 5 ± 2 μM, respectively. The compounds also inhibited HIV replication with potencies comparable with their integrase inhibitory potencies. Thus, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl]benzoic acid (25) and 5-bromo-3-[3-(4-bromophenyl)acryloyl]-2-hydroxybenzoic acid (15) inhibited HIV-1 replication with EC50 values of 7.3 and 8.7 μM, respectively. A PHASE pharmacophore hypothesis was developed and validated by 3D-QSAR, which gave a predictive r2 of 0.57 for an external test set of ten compounds. Phamacophore derived molecular alignments were used for CoMFA and CoMSIA 3D-QSAR modeling. CoMSIA afforded the best model with q2 and r2 values of 0.54 and 0.94, respectively. This model predicted all the ten compounds of the test set within 0.56 log units of the actual pIC50 values; and can be used to guide the rational design of more potent novel 3-keto salicylic acid integrase inhibitors.
CHROMENONE ANALOGS AS SIRTUIN MODULATORS
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Page/Page column 96-97, (2010/04/27)
Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for e
Chalcone derivatives and drugs containing the same
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, (2008/06/13)
PCT No. PCT/JP97/01652 Sec. 371 Date Nov. 17, 1998 Sec. 102(e) Date Nov. 17, 1998 PCT Filed May 16, 1997 PCT Pub. No. WO97/44306 PCT Pub. Date Nov. 27, 1997This invention relates to chalcone derivatives represented by the following formula (1): wherein A represents a phenyl group, a quinolyl group or the like, W represents a vinylene group or the like, and R1 to R5 each independently represent a carboxyl, cyano, alkyloxycarbonyl or like group, or salts of the chalcone derivatives, and also to drugs containing them as effective ingredients. These compounds have excellent cys-LT receptor antagonism, and are useful as antiallergic agents or the like.
Flavone derivative and medicine comprising the same
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, (2008/06/13)
This invention relates to a flavone derivative represented by the formula (1) or a salt thereof, and also to a medicine containing the same. wherein A represents H, halogen, phenyl, naphthyl, a group of the formula (2) in which X is H or halogen, B is -CH
Synthesis of carboxylated flavonoids as new leads for LTD4 antagonists
Zwaagstra,Timmerman,Abdoelgafoer,Zhang
, p. 861 - 874 (2007/10/03)
A series of 3'- and 5'-carboxylated chalcones, 6- or 8-carboxylated flavones and 6-carboxylated flavanones, -flavanols and -flavans were prepared. The compounds were tested for their inhibitory activities against leukotriene D4 (LTD4) induced contraction of guinea-pig ileum. A new and convenient synthetic route to 3-acetyl-2-hydroxybenzoic acid (Id), a key intermediate for the synthesis of 3'-carboxy-2'-hydroxychalcones and 8-carboxylated flavones, was developed. The activities of the tested compounds ranged from 0 to 63% inhibition at 10-5 M drug concentration against a single challenge of 10-8 M LTD4. Several compounds were tested in a radioligand binding assay against [3H]LTD4 on guinea-pig lung membrane. The quinoline-containing chalcone 12 and flavone 17 were found to exhibit significant but weak affinities for LTD4 receptors with pK(D)-values of 4.95 and 4.83, respectively and are interesting lead structures for the development of rigid LTD4 antagonists. In contrast, the rest of the compounds tested in the binding assay did not show significant displacement of the radioligand, implying that for these compounds the functional activity is probably not caused by competitive antagonism at the LTD4 receptor. The exact mechanism of the relaxant activity remains unclear.
Benzamide derivatives
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, (2008/06/13)
Benzamide derivatives of the formula:- STR1 wherein R1 represents a fluorine, chlorine or bromine atom, or an alkyl, alkoxy, alkylthio, alkylsulphonyl, alkanoylamino, alkylamino or alkylsulphamoyl group, each such group containing from 1 to 6 carbon atoms, a dialkylsulphamoyl, dialkylamino or dialkylcarbamoyl group (wherein the two alkyl groups may be the same or different and each contains from 1 to 4 carbon atoms), an alkanoyl, alkoxycarbonyl, alkoxycarbonylamino or alkylcarbamoyl group containing from 2 to 6 carbon atoms, or a hydroxy, formyl, nitro, trifluoromethyl, aryl, benzyloxycarbonylamino, amino, sulphamoyl, cyano, tetrazol-5-yl, carboxy, carbamoyl or aroyl group, and n represents an integer 1, 2 or 3, are new compounds possessing pharmacological properties, in particular properties of value in the treatment of respiratory disorders manifested by the interaction of tissue-fixed antibodies with specific antigens.
