- Design, synthesis, and biological evaluation of proteolysis targeting chimeras (PRoTACS) for the dual degradation of IGF-1R and SrC
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A focused PROTAC library was developed to degrade both IGF-1R and Src proteins, which are associated with various cancers. PROTACs with IGF-1R and Src degradation potentials were synthesized by tethering different inhibitor warhead units and the E3 ligase (CRBN) recruiting-pomalidomide with various linkers. The designed PROTACs 12a–b inhibited the proliferation and migration of MCF7 and A549 cancer cells with low micromolar potency (1–5 μM) in various cellular assays.
- Lee, Jeeyeon,Lee, Na Keum,Manda, Sudhakar,Oh, Dong-Chan
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- Novel biocompatible glucose-based deep eutectic solvent as recyclable medium and promoter for expedient multicomponent green synthesis of diverse three and four substituted pyrazole-4-carbonitrile derivatives
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A novel biocompatible glucose-based deep eutectic solvent (DES) is reported for the first time in the multicomponent synthesis of diverse three and four substituted pyrazole-4-carbonitrile derivatives under catalyst-free condition without using any harmful organic solvent even for purification of the products. The desired products were obtained with high degree of diversity from the reaction of malononitrile, aromatic aldehydes and various hydrazine derivatives as nitrogen source at room temperature within short reaction times and good to excellent product yields. The deep eutectic solvent was also recycled and reused at least four times with only a slight loss of efficiency. A plausible mechanism was also proposed indicating the role of DES hydrogen bonding in the reaction promotion.
- Aryan, Reza,Beyzaei, Hamid,Nojavan, Masoomeh,Rezaei, Meysam
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p. 4731 - 4744
(2017/07/22)
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- The conversion of isothiazoles into pyrazoles using hydrazine
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The conversion of isothiazoles into pyrazoles on treatment with hydrazine is investigated. The influence of various C-3, C-4 and C-5 isothiazole substituents and some limitations of this ring transformation are examined. When the isothiazole C-3 substituent is a good nucleofuge, 3-aminopyrazoles are obtained. However, when the 3-substituent is not a leaving group it is retained in the pyrazole product. Treatment of 4-bromo-3-chloro-5-phenylisothiazole 56 or 3-chloro-4,5-diphenylisothiazole 57 with anhydrous hydrazine at ca. 200 °C for a few minutes gives the corresponding 3-hydrazinoisothiazoles 61 and 64 respectively in high yields; the stability of these new hydrazines is investigated. 5,5′-Diphenyl-3,3′-biisothiazole-4,4′-dicarbonitrile 78 reacts with hydrazine to give 5,5′-diphenyl-3,3′-bi(1H-pyrazole)-4,4′-dicarbonitrile 79. Methylhydrazine reacts with 3-chloro-5-phenylisothiazole-4-carbonitrile 1 to give 3-(1-methylhydrazino)-5-phenylisothiazole-4-carbonitrile 83 and 3-amino-1-methyl-5-phenylpyrazole-4-carbonitrile 84. All products are fully characterised and rational mechanisms for the isothiazole into pyrazole transformation are proposed.
- Ioannidou, Heraklidia A.,Koutentis, Panayiotis A.
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experimental part
p. 7023 - 7037
(2009/12/06)
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- Polarized Ethylenes. IV. Synthesis of Polarized Ethylenes Using Thioamides and Methyl Dithiocarboxylates and their Application to Syntheses of Pyrazoles, Pyrimidines, Pyrazolopyrimidines, and 5-Azacyclazines
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Polarized ethylenes having both electron-donating (an amino or a methylthio group) and electron-accepting (cyano, carbamoyl, methyl ester) groups on the adjacent two olefinic carbon atoms were prepared by the condensation of S-alkylthioamidinium salts or
- Tominaga, Yoshinori,Matsuoka, Yoshiki,Oniyama, Yukio,Uchimura, Yoshimitsu,Komiya, Hirofumi,et al.
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p. 647 - 660
(2007/10/02)
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- A NOVEL PREPARATION OF POLARIZED ETHYLENES BY THE REACTION OF THIOAMIDES OR DITHIOCARBOXYLATES WITH TETRACYANOETHYLENE OXIDE. SYNTHESIS OF PYRAZOLES AND PYRIMIDINES
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Polarized ethylenes having both electron-donating (an amino or a methylthio group) and electron-accepting (two cyano groups) groups on the adjacent two olefinic carbon atoms were prepared by the reaction of thioamides or methyl dithiocarboxylates with tetracyanoethylene oxide in good yields.Reactions of these polarized ethylenes with hydrazine or guanidine carbonate gave the corresponding pyrazole and pyrimidine derivatives in good yields.
- Tominaga, Yoshinori,Matsuoka, Yoshiki,Kohra, Shinya,Hosomi, Akira
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p. 613 - 616
(2007/10/02)
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