313245-18-0

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-fluorobenzyl)-1H-indole-2,3-dione is used as a potential candidate for the development of new pharmaceutical drugs due to its unique structure and potential pharmacological properties. Its anti-inflammatory, antioxidant, and antimicrobial effects make it a promising compound for further research and development in the field of medicinal chemistry.
Further research and studies are required to fully understand the chemical and biological properties of 1-(4-fluorobenzyl)-1H-indole-2,3-dione and to explore its potential applications in the pharmaceutical industry.

Upstream product

• 91-56-5 indole-2,3-dione 
• 352-11-4 1-chloromethyl-4-fluorobenzene 
• 459-46-1 4-Fluorobenzyl bromide 

Downstream Products

• 522612-21-1 Cyano-[1-(4-fluoro-benzyl)-2-oxo-1,2-dihydro-indol-(3E)-ylidene]-acetic acid 
• 1332882-56-0 C₂₂H₁₆FN₃O₂ 
• 1373243-10-7 1-(4-fluorobenzyl)-3-hydroxy-3-(2-hydroxy-4-methoxyphenyl)indolin-2-one 
• 1373242-28-4 1-(4-fluorobenzyl)-3-hydroxy-3-(6-hydroxybenzo[d][1,3]dioxol-5-yl)indolin-2-one 
• 1373243-14-1 5-acetyl-1'-(4-fluorobenzyl)-6-hydroxy-2H-spiro[benzofuran-3,3'-indolin]-2'-one 
• 1373243-42-5 5-(2-bromoacetyl)-1'-(4-fluorobenzyl)-6-hydroxy-2H-spiro[benzofuran-3,3'-indolin]-2'-one 
• 1373243-46-9 5'-(1-(4-fluorobenzyl)-2-oxoindolin-3-yl)-6'-hydroxy-1'-methyl-spiro[cyclopropane-1,3'-indolin]-2'-one 
• 1373242-29-5 3-(6-(benzyloxy)benzo[d][1,3]dioxol-5-yl)-1-(4-fluorobenzyl)-3-hydroxyindolin-2-one 
• 1373242-33-1 1-(4-fluorobenzyl)-3-(2-hydroxy-2-methylpropyl)-3-(6-hydroxylbenzo[d][1,3]dioxol-5-yl)-indolin-2-one 
• 1373243-11-8 1-(4-fluorobenzyl)-3-(2-hydroxy-4-methoxyphenyl)indolin-2-one 
• 1373243-12-9 1'-(4-fluorobenzyl)-6-methoxy-2H-spiro[benzofuran-3,3'-indolin]-2'-one 
• 1373243-43-6 1'-(4-fluorobenzyl)-2H-spiro[benzo[1,2-b:5,4-b']difuran-3,3'-indoline]-2',5(6H)-dione 
• 1373241-86-1 C₂₈H₂₂FNO₄ 
• 1373241-87-2 C₂₈H₂₄FNO₄ 

Relevant academic research and scientific papers

Discovery of Isatin-Based Carbohydrazones as Potential Dual Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase

Using ligand-based design strategy, a set of isatin-3-carbohydrazones was designed, synthesized and evaluated for dual fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition properties. Compound 5-chloro-N′-(5-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 b) emerged as a potent MAGL inhibitor with nanomolar activity (IC50=3.33 nM), while compound 5-chloro-N′-(1-(4-fluorobenzyl)-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 j) was the most potent selective FAAH inhibitor (IC50=37 nM). Compound 5-chloro-N′-(6-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 c) showed dual FAAH-MAGL inhibitory activity with an IC50 of 31 and 29 nM respectively. Enzyme kinetics studies revealed that the isatin-based carbohydrazones are reversible inhibitors for both FAAH and MAGL. Further, blood-brain permeability assay confirmed that the lead compounds (13 b, 13 c, 13 g, 13 m and 13 q) are suitable as CNS candidates. Molecular dynamics simulation studies revealed the putative binding modes and key interactions of lead inhibitors within the enzyme active sites. The lead dual FAAH-MAGL inhibitor 13 c showed significant antioxidant activity and neuroprotection in the cell-based cytotoxicity assay. In summary, the study yielded three potent FAAH/MAGL inhibitor compounds (13 b, 13 c and 13 j) with acceptable pharmacokinetic profile and thus can be considered as promising candidates for treating neurological and mood disorders.

New cell cycle checkpoint pathways regulators with 2-Oxo-indoline scaffold as potential anticancer agents: Design, synthesis, biological activities and in silico studies

3-Arylidene-2-oxo-indoline derivatives are at the heart of a wide range of clinically, medicinally and biologically important compounds among the 2-oxo-indolines. A number of 3-arylidene-2-oxo-indolines have been approved for clinical application. Accordi

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

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.

Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer

In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates (5a–e and 7a–i) was designed and synthesised. The anticancer activity for compounds (5b–d, 7a, 7b, 7d and 7g) was measured against NCI-55 human cancer cell lines. Compound 5d was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels. Furthermore, all conjugates (5a–e and 7a–i) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds 5a and 5d (IC50 = 8.7 and 9.4 μM (5a), and 6.5 and 9.8 μM for (5d), respectively). Both compounds displayed selective cytotoxicity with good safety profile. In addition, both compounds provoked apoptosis in a dose dependent manner in SW-620 cells. Also, they significantly inhibited the anti-apoptotic Bcl2 protein expression and increased the cleaved PARP level that resulted in SW-620 cells apoptosis.

Palladium-Catalyzed Cascade Hydrosilylation and Amino-Methylation of Isatin Derivatives

We demonstrate that using palladium acetate as a catalyst for reduction of DMF and isatin derivatives by hydrosilanes, a cascade hydrosilylation and amino-methylation reaction can be realized. With DMF as a reactant and a solvent, the in-situ generated siloxymethylamine intermediate, an adduct of DMF and hydrosilanes, smoothly participates in the successive stages, providing a serials of Si, N-functionalized indolin-2-ones in moderate to good yields. This strategy exhibits high chemoselectivity toward carbonyl moieties reduction among the substrates. (Figure presented.).

Identifying new isatin derivatives with gsk-3β inhibition capacity through molecular docking and bioassays

The semi-synthesis of 11 isatin derivatives was achieved through bimolecular nucleophilic substitution and click chemistry. Seven new compounds were obtained. All chemical structures were determined by infrared spectroscopy (IR), nuclear magnetic resonanc

Synthesis, biological evaluation and in silico studies of certain oxindole–indole conjugates as anticancer CDK inhibitors

On account of their overexpression in a wide range of human malignancies, cyclin-dependent kinases (CDKs) are among the most validated cancer targets, and their inhibition has been featured as a valuable strategy for anticancer drug discovery. In this study, a hybrid pharmacophore approach was adopted to develop two series of oxindole–indole conjugates (6a–i and 9a–f) and carbocycle–indole conjugates (11a,b) as efficient antitumor agents with potential inhibitory action toward CDK4. All oxindole–indole conjugates, except 6i, 9b, and 9c efficiently affected the growth of the human breast cancer MCF-7 (IC50: 0.39 ± 0.05–21.40 ± 1.58 μM) and/or MDA-MB-231 (IC50: 1.03 ± 0.04–22.54 ± 1.67 μM) cell lines, whereas bioisosteric replacement of the oxindole nucleus with indane or tetralin rings (compounds 11a,b) diminished the anti-proliferative activity. In addition, hybrids 6e and 6f displayed effective cell cycle disturbance and proapoptotic capabilities in MCF-7 cells. Furthermore, the efficient anti-proliferative agents towards MCF-7 and/or MDA-MB-231 cell lines (6a–h, 9a, and 9e) were investigated for their potential inhibitory action toward CDK4. Hybrids 6a and 6e displayed good CDK4 inhibitory activity with IC50s equal 1.82 and 1.26 μM, respectively. The molecular docking study revealed that oxindole moiety is implicated in two H-bonding interactions via both (NH) and (C=O) groups with the key amino acids Glu94 and Val96, respectively, whereas the indole framework is stably accommodated in a hydrophobic sub-pocket establishing hydrophobic interactions with the amino acid residues of Ile12, Val20, and Gln98 lining this sub-pocket. Collectively, these results highlighted hybrids 6a and 6e as good leads for further optimization as promising antitumor drugs toward breast malignancy and CDK inhibitors.

Synthesis of isatin based N1-alkylated 3-β-C-glycoconjugated-oxopropylidene oxindoles as potent antiplasmodial agents

In an attempt to develop new antimalarial drugs, we have synthesized a new class of N-alkylated 3-glycoconjugated-oxopropylidene oxindoles starting from substituted isatins and glucopyranosyl propanone via a well-known cross-aldol reaction followed by deh

NHC-Catalyzed Aldol-Like Reactions of Allenoates with Isatins: Regiospecific Syntheses of γ-Functionalized Allenoates

An N-heterocyclic carbene (NHC) catalyzed γ-specific aldol-like reaction between allenoates and isatins has been achieved under mild conditions, giving trisubstituted allene derivatives bearing isatin moiety in moderate to good yields with high diastereoselectivity and excellent atom efficiency. The DFT computations indicated that the formation of the γ-adduct was more energetically favorable than that of the α-adduct. The result reported herein opens a new route for NHC-promoted allenoate-involved reaction.

Novel hydrazido benzenesulfonamides-isatin conjugates: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies

As a part of our ongoing efforts towards developing novel carbonic anhydrase inhibitors based on the isatin moiety, herein we report the synthesis and biological evaluation of novel sulfonamides (5a-h, 10a-g and 11a-c) incorporating substituted 2-indolinone moiety (as tail) linked to benzenesulfonamide (as zinc anchoring moiety) through a hydrazide linker. The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. All these isoforms were inhibited by the sulfonamides reported here in variable degrees. hCA I was inhibited with KIs in the range of 671.8: 3549.5 nM, hCA II in the range of 36.8: 892.4 nM; hCA IX in the range of 8.9: 264.5 nM, whereas hCA XII in the range of 9.0: 78.1 nM. In particular, compound 10b emerged as a single-digit nanomolar hCA IX and XII inhibitor (8.9 and 9.2 nM, respectively). Molecular docking studies carried out for compound 10b within the hCA II, IX and XII active sites allowed us to rationalize the obtained inhibition results.