2058-74-4Relevant articles and documents
Synthesis of novel 5-substituted indirubins as protein kinases inhibitors
Beauchard, Anne,Ferandin, Yoan,Frere, Stephane,Lozach, Olivier,Blairvacq, Melina,Meijer, Laurent,Thiery, Valerie,Besson, Thierry
, p. 6434 - 6443 (2006)
In an effort to identify new pharmacological inhibitors of disease-relevant protein kinases with increased potency and selectivity, we synthesized and evaluated new 5-substituted indirubins. The effects of 34 indirubin derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3, as well as on SH-SY5Y human neuroblastoma cell survival, were investigated.
AcOH-mediated dichloroimination of indoles using chloramine-B: A facile access to 2,3-functionalized indolines
Liu, Xiaozu,Hu, Qinghong,Yuan, Zeli,Liu, Peijun
, p. 7494 - 7497 (2014)
A new and mild method for the efficient synthesis of 3,3-dichloro-2-sulfonyliminoindolines via AcOH-mediated dichloroimination of indoles using chloramine-B is presented. Application of this method to the efficient construction of pyrrolidinoindoles and N-C3 linked pyrrolidinoindolines is demonstrated.
C-H Activation Relay (CHAR): An Efficient Construction of Isatin Skeleton by Aerobic Oxidation of Glycine Esters
Jia, Xiaodong,Zhu, Yingzu,Yuan, Yu,Zhang, Xuewen,Lü, Shiwei,Zhang, Liang,Luo, Liangliang
, p. 6033 - 6036 (2016)
Directed by the strategy of C-H activation relay (CHAR), an efficient construction of isatin skeleton was developed through catalytic oxidation of glycine esters. The mechanistic study reveals that the oxidation of the relatively active C-H bonds initiated the followed activation of remote and inert C-H bonds, and an intramolecular 1,6-hydrogen shift was involved as a key step.
New and efficient one-pot synthesis of functionalized γ-spirolactones mediated by vinyltriphenylphosphonium salts
Esmaili, Abbas Ali,Bodaghi, Asghar
, p. 1169 - 1171 (2003)
The addition of dimethyl acetylenedicarboxylate to isatin derivatives in the presence of triphenylphosphine leading to new highly functionalized γ-spirolactones is reported.
First X-ray structural characterization of isatin Schiff base derivative. NMR and theoretical conformational studies
Davidovich, Pavel,Novikova, Daria,Tribulovich, Vyacheslav,Smirnov, Sergey,Gurzhiy, Vlad,Melino, Gerry,Garabadzhiu, Alexander
, p. 450 - 455 (2014)
Isatin (1H-indole-2,3-dione) is an endogenous natural compound under intense development in medicinal chemistry. Here, we characterize isatin Schiff base derivative by X-ray crystallography. We describe a derivative that crystallizes E-isomer form in the triclinic space group P 1ˉ; a = 5.9580 (4) A?, b = 8.4184 (7) A?, c = 14.1801 (14) A?, α = 73.962 (8)°, β = 83.184 (7)°, γ = 81.143 (6)°. NMR data show that E-conformer interconverts to the Z-conformer when dissolved, this equilibrium weakly depends on the solvent type. The Z-isomer geometry and the energetics of ΔEE-Zinterconversion barriers were determined by quantum chemical calculations. The isomers are further characterized by means of FT-IR and UV-Vis spectroscopy.
[3 + 3] Formal Cycloadditions of Nitrones from Isatins and Azaoxyallyl Cations for Construction of Spirooxindoles
Lin, Weijia,Zhan, Gu,Shi, Minglin,Du, Wei,Chen, Yingchun
, p. 857 - 860 (2017)
A [3 + 3] formal cycloaddition reaction between in situ formed azaoxyallyl cations and nitrones from isatins has been developed, furnishing a spectrum of spiro[1,2,4-oxadiazinan-5-one]oxindoles in good to excellent yields with excellent diastereoselectivity. This method provides direct and efficient access to potentially bioactive spirooxindoles incorporating a six-membered heterocyclic scaffold.
Synthesis and biological evaluation of new [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines against Leishmania donovani
Gupta, Leena,Sunduru, Naresh,Verma, Aditya,Srivastava, Saumya,Gupta, Suman,Goyal, Neena,Chauhan, Prem M.S.
, p. 2359 - 2365 (2010)
A series of [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines were synthesized and screened for their in vitro antileishmanial activity against Leishmania donovani. Among all, 8 compounds have shown more than 90% inhibition against promastigotes and IC50 in the range of 4.01-57.78 μM against amastigotes. Compound 5, a triazino[5,6-b]indol-3-ylthio-1,3,5-triazine derivative was found to be the most active and least toxic with 20- & 10-fold more selectivity (S.I. = 56.61) as compared to that of standard drugs pentamidine and sodium stibogluconate (SSG), respectively.
Construction of spiro[indoline]oxindoles through one-pot thermal-induced [3+2] cycloaddition/silica gel-promoted fragmentation sequence between isatin ketonitrones and electron-deficient alkynes
Yang, Hai-Bin,Wei, Yin,Shi, Min
, p. 4088 - 4097 (2013)
One-pot thermal-induced [3+2] cycloaddition/silica gel-promoted fragmentation sequence between isatin ketonitrones and electron-deficient alkynes affords spiro[indoline]oxindoles in moderate to excellent yields along with good diastereoselectivities. The
TBHP Mediated Substrate Controlled Oxidative Dearomatization of Indoles to C2/C3-Quaternary Indolinones
Kothandapani, Jagatheeswaran,Reddy, Singarajanahalli Mundarinti Krishna,Thamotharan, Subbiah,Kumar, Shankar Madan,Byrappa, Kullaiah,Ganesan, Subramaniapillai Selva
, p. 2762 - 2767 (2018)
Oxidative dearomatization of indoles with 70 % aqueous tert-butylhydroperoxide (TBHP) in the absence of any metal salts/organic solvents gave the corresponding C2/C3-quaternary indolinones under open-air reaction conditions. The nature of substituent on the indole nitrogen dictates the type of product formed in these reactions. Free (NH)-indoles gave C2-quaternary indolinone derivatives whilst (NR)-indoles yielded C3-quaternary indolinones as the major product. Moreover, the addition of an excess amount of TBHP also facilitated the one-pot transformation of (NR)-indoles to the corresponding isatin derivatives.
Synthesis of novel functionalized 3-spiropyrrolizidine and 3-spiropyrrolidine oxindoles from Baylis-Hillman adducts of iatin and heteroaldehydes with azomethine ylides via [3+2]-cycloaddition
Shanmugam, Ponnusamy,Viswambharan, Baby,Madhavan, Suchithra
, p. 4095 - 4098 (2007)
A novel regioselective synthesis of a number of functionalized 3-spiropyrrolizidine and 3-spiropyrrolidine oxindoles from Baylis-Hillman adducts of satin and heteroaldehydes via [3+2] cycloaddition of azomethine ylides in excellent yields has been reported.
The application of Morita-Baylis-Hillman reaction: Synthetic studies on perophoramidine
Wu, Lin,Zhang, Qian-Ru,Huang, Ji-Rong,Li, Yang,Su, Fu,Dong, Lin
, p. 3966 - 3972 (2017)
A new concise methodology was developed for the synthesis of the two vicinal quaternary centers of the natural product perophoramidine. Key steps involved the Morita–Baylis–Hillman reaction, reductive cyclization and allylic alkylation. Moreover, most con
Base-mediated allylation of N-2,2,2-trifluoroethylisatin ketimines and its application in aza-Prins reactions
Kim, Jaehwan,Yeon Park, Se,Jung, Myeongjin,Jang, Woo Cheol,Ko, Haye Min
supporting information, (2021/12/01)
The aza-Prins reaction of allylic imines triggered by N-2,2,2-trifluoroethylisatin ketimine is accomplished for the synthesis of spirooxindole derivatives involving trifluoromethyl group in the presence of TMSX. This cyclization reaction is operationally simple and proceeds under mild conditions using non-toxic reagents. Notably, while the previous our work could not be compatible with TMSX (X = Cl, I, etc) in one-pot process, this work describes successful aza-Prins reaction with TMSX (X = Cl, I, etc) via step-by-step process.
Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations
Eldehna, Wagdy M.,El Hassab, Mahmoud A.,Abo-Ashour, Mahmoud F.,Al-Warhi, Tarfah,Elaasser, Mahmoud M.,Safwat, Nesreen A.,Suliman, Howayda,Ahmed, Marwa F.,Al-Rashood, Sara T.,Abdel-Aziz, Hatem A.,El-Haggar, Radwan
supporting information, (2021/03/15)
In the current medical era, human health is experiencing numerous challenges, particularly the human malignancies. Therefore, the therapeutic arsenal for these malignancies is to be inexorably enhanced with new treatments that target tumor cells in a selective manner. In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors. The large tricyclic TBI motif is anticipated to achieve a plethora of hydrophobic interactions within the CDK2 binding site. The growth of the two examined cell lines was significantly inhibited by most the prepared hybrids with IC50 ranges; (2.60 ± 1.47–20.90 ± 1.17 μM, against MDA-MB-231) and (1.27 ± 0.06–16.83 ± 0.95 μM, against MCF-7). In particular, hybrids 7a, 7d and 10a displayed potent dual activity against the examined cell lines, and thus selected for further investigations. They exerted a significance alteration in the cell cycle progression, in addition to an apoptosis induction within both MDA-MB-231 and MCF-7 cells. Furthermore, 7a, 7d and 10a displayed potent CDK2 inhibitory action (IC50 = 96.46 ± 5.3, 26.24 ± 1.4 and 42.95 ± 2.3 nM, respectively). The docking simulations unveiled, as expected, the ability of the TBI ring to well-accommodate and establish several hydrophobic interactions within a hydrophobic pocket in the CDK2 binding site. Also, the docking simulations highlighted the significance of incorporation of the hydrazide linker and isatin unsubstituted (NH) functionality in the H-bonding interactions. Interestingly, the most potent CDK2 inhibitor 7d achieved the best binding score (-11.2 Kcal/mole) and formed the most stable complex with CDK2 enzyme (RMSD = 1.24 ?) in a 100 ns MD simulation. In addition, the MM-PBSA calculations ascribed the lowest binding free energy to the 7d–CDK2 complex (?323.69 ± 15.17 kJ/mol). This could be attributed to an incorporation of the 5-OCH3 group that was engaged in an extra hydrogen bonding with key THR14 amino acid residue. Finally, these results suggested hybrid 7d as a good candidate for further optimization as promising breast cancer antitumor agent and CDK2 inhibitor.
