“…The authors used the presence of three nucleophilic centers in the malonothioamides 212 and three electrophilic centers in methyl acetylpyruvate 213 for the single-stage production of 4-thioxopyrrolo [3,4- [107,108]. It was found that 1-methyl-1,4-dihydro-2H-3,1-benzoxazine-2,4-diones 215 are transformed by the action of ethoxy(thio)carbonylthioacetamides into 3-thiocarbamoylquinolines 216 [107]. It is also possible to assign the condensations of Meldrum's acid 100 with N-(4-bromophenyl)-1-amino-1-thiomalonamide 217 and 2-chlorobenzaldehyde 67 to recyclizations [108].…”
Section: Cyclization Of Malonodithioamides With 124-trielectrophilesmentioning
Data from the last six years on the heterocyclization of thioamides containing an active methylene group are analyzed and classified.At the present time there has been a considerable increase in the number of publications on the chemistry of thioamides, and this is explained by the value of the compounds as initial reagents for further transformations and particularly for the synthesis of various sulfur-and nitrogen-containing heterocycles [1][2][3][4][5][6][7][8]. The enormous practical significant of the latter is common knowledge -they have found application as drugs, pesticides, dyes, and preservatives.Thioamides with an active methylene group are attractive synthesis units for the production of heterocycles. These polyfunctional compounds can be represented by the formula R 3 -CH 2 CS-NR 1 R 2 (where R 1 , R 2 = H, Alk, Ar; R 3 is an electron-withdrawing group such as CN, AlkCO, ArCO, (AlkO) 2 PO, AlkSO 2 , ArSO 2 , NO 2 ). The presence of another reaction center (the methylene group) makes it possible to use them as N-С-С and S-C-C components for various condensations [1][2][3][4][5][6][7][8]. A special feature of such substrates is the ability to react both with dinucleophilic and with dielectrophilic and dipolar reagents. As a rule the products of these heterocyclizations contain functional groups, which makes it possible to achieve their modification or annelation. Such characteristics of thioamides with an active methylene group substantially increase their synthetic potential and extend the range of accessible heterosystems, while the use of modern physical methods of investigation (X-ray crystallographic analysis and 1D and 2D NMR spectroscopy) makes it possible to establish the structure of the obtained compounds unambiguously. The presence of biological activity in the products of these transformations also attracts investigators to this subject [5][6][7][8].The reason for the appearance of this review was the increasing need for generalization and classification of new information on the heterocyclization of such thioamides that had not been included in previous reviews [2][3][4][5] and also to define the trends in the study of these processes. Since one of the most important reports in this field is the review [1] we undertook an analysis of the literature that has appeared in the last six years.
“…The authors used the presence of three nucleophilic centers in the malonothioamides 212 and three electrophilic centers in methyl acetylpyruvate 213 for the single-stage production of 4-thioxopyrrolo [3,4- [107,108]. It was found that 1-methyl-1,4-dihydro-2H-3,1-benzoxazine-2,4-diones 215 are transformed by the action of ethoxy(thio)carbonylthioacetamides into 3-thiocarbamoylquinolines 216 [107]. It is also possible to assign the condensations of Meldrum's acid 100 with N-(4-bromophenyl)-1-amino-1-thiomalonamide 217 and 2-chlorobenzaldehyde 67 to recyclizations [108].…”
Section: Cyclization Of Malonodithioamides With 124-trielectrophilesmentioning
Data from the last six years on the heterocyclization of thioamides containing an active methylene group are analyzed and classified.At the present time there has been a considerable increase in the number of publications on the chemistry of thioamides, and this is explained by the value of the compounds as initial reagents for further transformations and particularly for the synthesis of various sulfur-and nitrogen-containing heterocycles [1][2][3][4][5][6][7][8]. The enormous practical significant of the latter is common knowledge -they have found application as drugs, pesticides, dyes, and preservatives.Thioamides with an active methylene group are attractive synthesis units for the production of heterocycles. These polyfunctional compounds can be represented by the formula R 3 -CH 2 CS-NR 1 R 2 (where R 1 , R 2 = H, Alk, Ar; R 3 is an electron-withdrawing group such as CN, AlkCO, ArCO, (AlkO) 2 PO, AlkSO 2 , ArSO 2 , NO 2 ). The presence of another reaction center (the methylene group) makes it possible to use them as N-С-С and S-C-C components for various condensations [1][2][3][4][5][6][7][8]. A special feature of such substrates is the ability to react both with dinucleophilic and with dielectrophilic and dipolar reagents. As a rule the products of these heterocyclizations contain functional groups, which makes it possible to achieve their modification or annelation. Such characteristics of thioamides with an active methylene group substantially increase their synthetic potential and extend the range of accessible heterosystems, while the use of modern physical methods of investigation (X-ray crystallographic analysis and 1D and 2D NMR spectroscopy) makes it possible to establish the structure of the obtained compounds unambiguously. The presence of biological activity in the products of these transformations also attracts investigators to this subject [5][6][7][8].The reason for the appearance of this review was the increasing need for generalization and classification of new information on the heterocyclization of such thioamides that had not been included in previous reviews [2][3][4][5] and also to define the trends in the study of these processes. Since one of the most important reports in this field is the review [1] we undertook an analysis of the literature that has appeared in the last six years.
“…The structure of linomide has served as the prototype for the synthesis of a variety of analogues in an effort to optimize this lead compound. [10][11][12][13][14] Another synthetic quinolinone derivative, rebamipide 15 (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl]propionic acid, Figure 1) is an effective antioxidant and antiulcer agent, mediating its pharmacological activity mainly by increasing endogenous prostaglandin synthesis and by ROS scavenging. 16 The structural characteristics of rebamipide that have been shown to be important for scavenging the hydroxyl radical are the 3,4-double bond and the 2-oxo functionality of the quinolinone moiety and the carbonyl part of the amido group in conjunction with a p-chlorobenzyl function.…”
Section: Introductionmentioning
confidence: 99%
“…Linomide ( N -phenylmethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide, Figure ), is a synthetic immunomodulator, which is effective against various types of cancers and autoimmune disorders, such as multiple sclerosis (MS), rheumatoid arthritis, systemic lupus erythematosis, and experimental autoimmune encephalomyelitis. The structure of linomide has served as the prototype for the synthesis of a variety of analogues in an effort to optimize this lead compound. − 1 …”
A series of N-substituted-quinolinone-3-aminoamides and their hybrids containing the alpha-lipoic acid functionality were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity. The new compounds were evaluated for their antioxidant activity and for their ability to inhibit in vitro lipoxygenase as well as for their anti-inflammatory activity in vivo. In general, the derivatives were found to be potent antioxidant or anti-inflammatory agents. The results are discussed in terms of structure-activity relationships and an attempt is made to define the structural features required for activity.
“…However, it seems that NBS as well as oxygen from air can play important roles in the preparation process of 5-bromoisatoic anhydride from isatin. In our opinion, the presented methodology can be complementary to existing methods for the synthesis of this type of compounds [37][38][39][40][41].…”
A series of 6-substituted quinazolinone derivatives were prepared by the reaction of 6-bromoquinazolinones with aryl or alkyl amines and thiols, in the presence of a Pd(OAc) 2 /Xantphos system, under Buchwald-Hartwig-type reaction conditions. The 6-bromoquinazolinones were obtained in the three-components reaction of 5-bromoisatoic anhydride, triethyl orthoformate and an appropriate amine. Biological screening of the potential cytotoxicity of synthesized compounds on HT29 and HCT116 cell lines, as well as on the lymphocytes, showed that some derivatives of quinazolinone have significant anticancer activities. The detailed synthesis, spectroscopic data, and biological assays were reported.
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