Abstract
As a member of heterocyclic compounds, indole possesses a diverse set of biological activities. Studies on the structure-activity relationship of 2-indolinones have shown that they are important bioactive compounds in the field of pharmaceutical chemistry. Isatin and structures bearing isatin scaffold are derivatives of indole, which have shown to be of biological and pharmacological significance. This review focuses on different ways of obtaining compounds containing isatin structure, considering both earlier and recent methods of synthesis. The syntheses given herein were grouped into three categories, syntheses using anilines as their starting substance, synthetic methods based on the oxidation of indoles, and finally, due to the extensive research going on 5-substituted isatins and their possible pharmacological efficacy, pathways for synthesizing 5-amino and 5-sulfamoylisatins were gathered to underline the importance of 2-indolinone and isatin derivatives as prospective therapeutic compounds in current and future drug discovery studies.
Keywords: 2-indolinones, 5-aminoisatins, 5-sulfamoylisatins, heterocycles, indoles, isatins, synthesis.
Graphical Abstract
[http://dx.doi.org/10.1248/cpb.46.886] [PMID: 9621425]
[http://dx.doi.org/10.1016/S0040-4020(01)96609-8]
[http://dx.doi.org/10.1590/S0103-50532001000300002]
[http://dx.doi.org/10.1055/s-2006-959766] [PMID: 17230369]
[http://dx.doi.org/10.7164/antibiotics.39.162] [PMID: 3949628]
[http://dx.doi.org/10.3891/acta.chem.scand.50-0443]
[http://dx.doi.org/10.1002/prac.18400190161]
[http://dx.doi.org/10.1525/hsns.2014.44.4.319]
[http://dx.doi.org/10.1039/C2CP42539D] [PMID: 23232916]
[http://dx.doi.org/10.5935/0103-5053.20130089]
[http://dx.doi.org/10.1016/j.bmc.2017.05.029] [PMID: 28545816]
[http://dx.doi.org/10.1016/j.bioorg.2020.104202] [PMID: 32892069]
[http://dx.doi.org/10.4103/0110-5558.72428] [PMID: 22247869]
[http://dx.doi.org/10.1016/S0928-0987(02)00077-5] [PMID: 12128166]
[http://dx.doi.org/10.3109/14756366.2013.800058] [PMID: 23738950]
[http://dx.doi.org/10.1016/j.bmc.2006.10.035] [PMID: 17088067]
[http://dx.doi.org/10.1016/j.bmcl.2005.04.027] [PMID: 15896959]
[http://dx.doi.org/10.1016/j.ejmech.2014.10.056] [PMID: 25462246]
[http://dx.doi.org/10.1016/j.bmc.2016.02.036] [PMID: 26951893]
[http://dx.doi.org/10.1016/S0223-5234(02)01416-2] [PMID: 12446050]
[http://dx.doi.org/10.2147/DDDT.S227862] [PMID: 32099332]
[http://dx.doi.org/10.2174/9781608054961113020008]
[http://dx.doi.org/10.3389/fmolb.2020.627272] [PMID: 33614708]
[http://dx.doi.org/10.1007/s41061-019-0240-9] [PMID: 31073777]
[http://dx.doi.org/10.1016/j.bioorg.2019.103162] [PMID: 31382058]
[http://dx.doi.org/10.1016/j.molstruc.2020.128900]
[http://dx.doi.org/10.1016/j.ejmech.2009.12.001] [PMID: 20045221]
[http://dx.doi.org/10.1016/j.ejmech.2018.12.017] [PMID: 30654239]
[http://dx.doi.org/10.1016/j.molstruc.2021.130495]
[http://dx.doi.org/10.1016/S1734-1140(13)71007-7] [PMID: 23744416]
[http://dx.doi.org/10.1080/14756360701746179] [PMID: 19005943]
[http://dx.doi.org/10.1016/j.bmc.2007.05.063] [PMID: 17561405]
[http://dx.doi.org/10.1016/j.bmcl.2005.07.046] [PMID: 16115762]
[http://dx.doi.org/10.1016/j.bfopcu.2014.02.001]
[http://dx.doi.org/10.3109/14756366.2016.1149479] [PMID: 26928426]
[PMID: 15907222]
[http://dx.doi.org/10.1111/j.1749-6632.1965.tb12541.x] [PMID: 5216633]
[http://dx.doi.org/10.1007/BF01314907] [PMID: 539911]
[http://dx.doi.org/10.1200/JCO.2005.02.2194] [PMID: 16314617]
[http://dx.doi.org/10.1172/JCI69738] [PMID: 24382387]
[http://dx.doi.org/10.1074/jbc.275.21.16007] [PMID: 10821855]
[http://dx.doi.org/10.1016/j.ejmech.2016.01.030] [PMID: 26840366]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1860] [PMID: 19470739]
[http://dx.doi.org/10.1039/C8MD00585K] [PMID: 30996856]
[http://dx.doi.org/10.1021/acs.joc.1c01269] [PMID: 34269051]
[http://dx.doi.org/10.2165/00003495-200262080-00015] [PMID: 12010089]
[http://dx.doi.org/10.2165/00003495-200060010-00007] [PMID: 10929932]
[http://dx.doi.org/10.1002/hlca.19190020125]
[http://dx.doi.org/10.1007/BF02290733]
[http://dx.doi.org/10.1002/prac.19221050111]
[http://dx.doi.org/10.1016/S0040-4020(01)86993-3]
[http://dx.doi.org/10.1021/jm00229a006] [PMID: 781245]
[http://dx.doi.org/10.1021/jo00428a016]
[http://dx.doi.org/10.1016/0040-4039(96)00920-3]
[http://dx.doi.org/10.1016/0040-4039(94)85299-5]
[http://dx.doi.org/10.1021/jo00353a033]
[http://dx.doi.org/10.1021/jm00377a001] [PMID: 6436487]
[http://dx.doi.org/10.1016/S0040-4039(98)01719-5]
[http://dx.doi.org/10.1055/s-1999-3085]
[http://dx.doi.org/10.1023/A:1017575504084]
[http://dx.doi.org/10.1016/S0040-4039(01)90407-1]
[http://dx.doi.org/10.1002/jhet.8]
[http://dx.doi.org/10.1021/ja103426d] [PMID: 20540581]
[http://dx.doi.org/10.1021/ol402750r] [PMID: 24191737]
[http://dx.doi.org/10.1002/ejoc.201600143]
[http://dx.doi.org/10.1016/j.ejmech.2018.10.068] [PMID: 30445264]
[http://dx.doi.org/10.1016/j.tetlet.2014.06.062]
[http://dx.doi.org/10.1039/c4ob00118d] [PMID: 24740324]
[http://dx.doi.org/10.1039/C3OB42024H] [PMID: 24281127]
[http://dx.doi.org/10.1016/j.tetlet.2012.12.035] [PMID: 23467398]
[http://dx.doi.org/10.1039/c3cc44435j] [PMID: 23945918]
[http://dx.doi.org/10.1039/c3ra40657a]
[http://dx.doi.org/10.1021/jo500550d] [PMID: 24787642]
[http://dx.doi.org/10.1021/acs.joc.5b00581] [PMID: 25906247]
[http://dx.doi.org/10.1002/anie.201109027] [PMID: 22378689]
[http://dx.doi.org/10.1016/j.tetlet.2017.10.057]
[http://dx.doi.org/10.1021/ol501203q] [PMID: 24850466]
[http://dx.doi.org/10.1055/s-0036-1591904]
[http://dx.doi.org/10.1055/s-0036-1589106]
[http://dx.doi.org/10.1055/s-0036-1590965]
[http://dx.doi.org/10.1016/j.tetlet.2017.03.060]
[http://dx.doi.org/10.1021/acscatal.6b01969]
[http://dx.doi.org/10.1055/s-2007-965930]
[http://dx.doi.org/10.1016/j.tet.2019.02.033]
[http://dx.doi.org/10.1016/j.ntt.2009.12.005] [PMID: 20034560]
[http://dx.doi.org/10.2174/1568026614666140530104344] [PMID: 24875768]
[http://dx.doi.org/10.1007/s11030-018-09910-7] [PMID: 30612259]
[http://dx.doi.org/10.1016/j.bmc.2006.05.036] [PMID: 16759872]
[http://dx.doi.org/10.1126/science.1242005] [PMID: 24288327]
[http://dx.doi.org/10.1016/j.ejmech.2011.10.020] [PMID: 22037252]
[http://dx.doi.org/10.1111/j.1747-0285.2012.01399.x] [PMID: 22540392]
[http://dx.doi.org/10.1111/cbdd.12265] [PMID: 24636345]
[http://dx.doi.org/10.1055/s-1997-789]
[http://dx.doi.org/10.1021/ja012610k] [PMID: 12022838]
[http://dx.doi.org/10.1021/ja035483w] [PMID: 12769573]
[http://dx.doi.org/10.1021/acschemneuro.0c00448] [PMID: 33073564]
[http://dx.doi.org/10.1021/jm0100537] [PMID: 11384246]
[http://dx.doi.org/10.1021/cc0100316] [PMID: 12217013]
[http://dx.doi.org/10.1016/j.ejmech.2005.07.011] [PMID: 16169127]
[http://dx.doi.org/10.1016/0379-6779(90)90184-M]
[http://dx.doi.org/10.1021/jm8002526] [PMID: 18680359]
[http://dx.doi.org/10.1021/jm900135r] [PMID: 19326941]
[http://dx.doi.org/10.1016/j.bmc.2013.11.028] [PMID: 24316352]