2438-71-3

Upstream product

• 106-40-1 4-bromo-aniline 
• 66475-83-0 N-(4-bromophenyl)-2-(hydroxyimino) acetamide 
• 87-48-9 5-Bromo-1H-indole-2,3-dione 
• 6326-79-0 6-bromoisatin 
• 443-69-6 5-fluoro-1H-indole-2,3-dione 

Downstream Products

• 352461-95-1 Mesoxalic acid dinitrile (4-bromo-2-cyanophenyl) hydrazone 
• 20870-78-4 5-bromo-2-indolin-2-one 
• 552332-19-1 5-bromo-3,3-difluoro-2,3-dihydro-1H-indol-2-one 
• 180904-63-6 (4,5-Diphenyl-1H-imidazol-2-ylsulfanyl)-acetic acid [5-bromo-2-oxo-1,2-dihydro-indol-(3Z)-ylidene]-hydrazide 
• 1026584-33-7 (5-Phenyl-[1,3,4]oxadiazol-2-ylsulfanyl)-acetic acid [5-bromo-2-oxo-1,2-dihydro-indol-(3Z)-ylidene]-hydrazide 

Relevant academic research and scientific papers

Synthesis and pharmacological screening of new isatin-3-[N2-(benzimidazol-1-acetyl)]hydrazone

Twenty new isatin-3-[N2-(benzimidazol-1-acetyl)]hydrazones (IV) were synthesized from ten different isatin-3-[N2–(chloroacetyl)] hydrazones (III) by reacting with benzimidazole and 2-methyl benzimidazole. The intermediates were obtained from isatin hydrazones (II) on condensation with chloroacetyl chloride. These compounds were characterized by IR, 1H NMR and mass spectra. All the compounds were screened for antimicrobial, antioxidant and cytotoxic activity. Some of the new compounds showed promising antibacterial and antifungal activity.

Novel [(3-indolylmethylene)hydrazono]indolin-2-ones as apoptotic anti-proliferative agents: design, synthesis and in vitro biological evaluation

On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a–r, 9a–f and 11a–c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that N-propylindole derivatives were the most active compounds such as 6n (MCF-7; IC50=1.04 μM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay. Also, 6n increased the expression of caspase-3, caspase-9, cytochrome C and Bax and decreased the expression of Bcl-2. Moreover, compounds 6i, 6j, 6n and 6q generated ROS by significant increase in the level of SOD and depletion of the levels of CAT and GSH-Px in MCF-7.

Solvent Effects: Syntheses of 3,3-Difluorooxindoles and 3-Fluorooxindoles from Hydrazonoindolin-2-one by Selectfluor

Efficient syntheses of 3,3-difluorooxindoles and 3-fluorooxindoles via fluorination of hydrazonoindolin-2-one with Selectfluor are reported. Under different solvent conditions, this method produced 3,3-difluorooxindoles and 3-fluorooxindoles selectively. The broad substrate scope and mild reaction conditions make this transformation a valuable method in drug discovery and development.

New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres

The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC50 values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC50 value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC50 value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC50 value less than 0.8 μM.

Lewis acid-promoted direct synthesis of N-unsubstituted hydrazones via the reaction of hydrazine with acetophenone and isatin derivatives

Hydrazones 2–22 were synthesized via the reaction of acetophenone with isatin derivatives and anhydrous hydrazine promoted by BF3 as a Lewis acid at 0°C. Structures of the synthesized hydrazones were determined on the basis of NMR and X-ray crystallograph

Catalyst free, multicomponent-tandem synthesis of spirooxindole-indazolones and spirooxindole-pyrazolines: A glycerol mediated green approach

The development of a versatile new one pot, catalyst free, multicomponent-tandem strategy for assembly of spirooxindole-indazolones and spirooxindole-pyrazolines is described. The reported protocol includes several advantages like environmental friendliness, cost effectiveness, high atom economy, short reaction times and high yields. The reported method is the first green synthesis of spirooxindole-indazolones and spirooxindole-pyrazolines. This journal is

A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: Construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters

A cinchona alkaloid catalyzed diastereoselective and enantioselective sulfa-Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and isoindigos has been successfully developed to afford the highly congested bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters in high yields (up to 91%), excellent diastereoselectivities (up to >20 : 1 dr), and good enantioselectivities (up to 98% ee). Some synthetic transformations of the reaction products were also studied.

Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents

A hybrid pharmacophore approach was adopted to design and synthesize new series of isatin-pyridine hybrids. All the newly prepared hybrids (5a-o, 8 and 11a-d) were in vitro evaluated for their anti-proliferative activity against three human cancer cell lines, namely HepG2 hepatocellular carcinoma, A549 lung cancer and MCF-7 breast cancer. Compound 8 emerged as the most active member against HepG2 cell line (ICinf50/inf = 2.5 ± 0.39 μM), with 2.7-fold increased activity than the reference drug, doxorubicin (ICinf50/inf = 6.9 ± 2.05 μM). Whilst, compound 11c was found to be the most potent counterpart against A549 and MCF-7 cell lines with ICinf50/inf values of 10.8 ± 1.15 and 6.3 ± 0.79, respectively. The weightiness of the utilization of non-cleavable linker, as the chalcone linker, and simplification of the first group, was explored via the SAR study. Furthermore, a QSAR model was built to explore the structural requirements controlling the cytotoxic activities. Notably, the predicted activities by the QSAR model were very close to those experimentally observed, hinting that this model could be safely applied for prediction of more efficacious hits comprising the same skeletal framework. Finally, a theoretical kinetic study was established to predict the ADME of the active hybrids.

Synthesis of new 2-substituted-[1,3,4]-oxadiazino-[5,6-b]-indoles with H1-antihistaminic, antimuscarinic and antimicrobial activity

New 2-substituted-[1,3,4]-oxadiazino-[5,6-b]-indoles have been prepared and tested for their antibacterial, antifungal, H1-anti-histaminic and antimuscarinic activities. Among them, compounds 5b, 5d, 5k exhibited higher H1-antihistaminic activity than pheniramine maleate. Compounds 5c, 5d showed higher antibacterial activity than ampicillin against Staphylococcus aureus and E. coli, respectively.

SEMICARBAZONES AND THIOSEMICARBAZONES OF THE HETEROCYCLIC SERIES. XLVII. ACYLATION OF ISATIN

Contrary to previous data, the acylation of isatin by carboxylic acid anhydrides in the presence of perchloric acid leads to the formation not of the O-acyl derivatives but of the N-acyl derivatives, which have a noncoplanar structure.Their transformation into isatin hydrazone and oxime is due to hydrolysis of the N-acyl group.In alcohol solutions the N-acylisatins rapidly open the five-membered ring with the addition of an alcohol molecule.