- Oxindole-based intraocular pressure reducing agents
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The study represents the new findings at the crossroads of chemistry and medicine, particularly between medicinal and organic chemistry and ophthalmology. In this work we describe how the chemical reactivity of indolinone scaffold may be used to create small molecule ligands with strong biological response comparable with and larger than that of endogenous hormone. The synthesis of oxindole-based melatonin and 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) analogues was proposed and their ability to influence intraocular pressure (IOP) was studied in vivo. Time-dependent study revealed the prolonged effect (more than 6?h) of the lead-compound. This effect in combination with high IOP reducing effect (41?±?6%) in low concentrations of the active compound (0.1?wt%) and with high water solubility represents a great potential of low-cost oxindole derivatives as potent antiglaucoma agents.
- Zaryanova, Ekaterina V.,Lozinskaya, Nataly A.,Beznos, Olga V.,Volkova, Maria S.,Chesnokova, Nataly B.,Zefirov, Nikolay S.
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supporting information
p. 3787 - 3793
(2017/07/27)
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- Utility of the pfitzinger reaction in the synthesis of novel quinoline derivatives and related heterocycles
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2-(2-Amino-3,5-dinitrophenyl)-2-oxoacetic acid (2) was obtained from hydrolysis of 5,7-dinitroisatin (1) in alkaline media. A novel quinoxaline derivative (3) was synthesized from the reaction of the same compound (1) with o-phenylenediamine. Reacting 2 with ethyl 3-oxo-3-phenylpropanoate yields 6,8-dinitro-2-phenylquinoline-3,4-dicarboxylic acid (4). Then, 4 was converted into new quinoline-diacylchloride, quinoline-ester, quinoline-dicarboxamide, pyridazine, and pyrroledione derivatives (5, 6a, 6b, 6c, 6d, 7a, 7b, 7c, 7d, 8, 9, 10a, 10b, 10c, 10d, 11a, 11b, 12) with SOCl2, alcohols, amines, and hydrazines, respectively. The structures of synthesized compounds were clarified by 1H NMR, 13C NMR, IR, mass and elemental analysis methods.
- Goek, Dervis,Kasymogullari, Rahmi,Cengiz, Mustafa,Mert, Samet
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p. 224 - 232
(2014/02/14)
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- Syntheses of gem-dinitro heterocyclic compounds, their ring-opening reactions and transformations into indoles, indazoles and benzoxazinones
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The synthesis of some novel 3,3,5,7-tetranitrooxindoles and 4,4- dinitropyrazol-5-ones and their behaviour towards various nucleophiles and electrophiles are reported. Reactions with hydroxide ions or secondary amines produced salts of e.g. 2-amino-3,5-dinitrophenyldinitromethane, which subsequently could be further transformed into indazoles, indoles or benzoxazinones depending upon substrate and conditions used. Mechanisms are discussed.
- Bergman, Jan,Bergman, Solveig,Brimert, Thomas
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p. 10447 - 10466
(2007/10/03)
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- Formation of 3,3,5,7-tetranitrooxindole and 3,5,7-trinitroindazole by nitration of oxindole
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Nitration (HNO3/H2SO4) of oxindole gave 3,3,5,7-tetranitrooxindole (1c), which readily underwent ring-opening and decarboxylation to 4,6-dinitro-2-(dinitromethyl)aniline (4b), which in turn could be cyclized to 3,5,7-trinitroindazole (5).
- Bergman, Jan,Bergman, Solveig
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p. 9263 - 9266
(2007/10/03)
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