3416-18-0

Usage

InChI:InChI=1/C8H7NO2/c10-6-1-2-7-5(3-6)4-8(11)9-7/h1-3,10H,4H2,(H,9,11)

Upstream product

• 121989-51-3 5-Hydroxy-1-methoxy-1,3-dihydro-indol-2-one 
• 108274-39-1 ethyl 2-(4-methoxy-2-nitrophenyl)acetate 
• 10298-80-3 2-chloro-5-methoxynitrobenzene 
• 10565-15-8 diethyl 2-(4-methoxy-2-nitrophenyl)malonate 
• 7699-19-6 6-methoxyoxindole 
• 39755-95-8 5-methoxyisatine 
• 7699-18-5 5-methoxyindolin-2-one 
• 451-81-0 2-(2-fluorophenyl)acetyl chloride 
• 59-48-3 2-oxoindole 
• 56473-79-1 5-methoxy-6-methyl-1,3-dihydro-2H-indol-2-one 
• 65816-14-0 1-methoxyindolin-2-one 
• 22303-36-2 N-(4-methoxyphenyl)-2-chloroacetamide 
• 66866-41-9 2-Ethoxy-5-hydroxy-3-indolcarbonsaeure-ethylester 
• 121990-14-5 N-chloro-2-(2-fluorophenyl)-N-methoxyacetamide 

Downstream Products

• 120109-85-5 5-Hydroxy-2-oxo-2,3-dihydro-indole-1-carboxylic acid (4-chloro-phenyl)-amide 
• 333728-93-1 C₂₀H₁₉N₅O₄ 
• 1087343-89-2 C₂₃H₁₉N₃O₄S 

Relevant academic research and scientific papers

Synthesis and antitumor activity of 1,5,6-substituted E-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones

Synthesis and antitumor activity of new E-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones are described. All compounds prepared were active in the primary test (three human cell lines) and entered the second level (60 human cell lines). The most active antitumor derivatives bear the same substituents in the chloroindole ring and are not CDK1 inhibitors. A COMPARE analysis showed that they could act as tubulin binders. In most cell lines, E-3-(2-chloro-5-methoxy-6-methyl-3-indolylmethylene)-1,3-dihydroindol-2-one was a growth inhibitor more potent than vincristine.

Design, synthesis and biological evaluation of novel human monoamine oxidase B inhibitors based on a fragment in an X-ray crystal structure

Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC50 = 3 nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems.

Photoinduced Isomerization and Hepatoxicities of Semaxanib, Sunitinib and Related 3-Substituted Indolin-2-ones

3-Substituted indolin-2-ones are an important class of compounds that display a wide range of biological activities. Sunitinib is an orally available multiple tyrosine kinase inhibitor that has been approved by the US Food and Drug Administration (FDA) for the treatment of renal cell cancer. Sunitinib and a related compound, semaxanib, exist as thermodynamically stable Z isomers, which photoisomerize to E isomers in solution. In this study, 17 3-substituted indolin-2-ones were synthesized, and the kinetics of their photoisomerization were studied by 1H NMR spectroscopy. The rate constants for photoisomerization ranged from 0.009 to 0.048 h-1. Selected compounds were tested for cytotoxicity in the TAMH liver cell line. E/Z mixtures of four compounds were also assessed for toxicity in the TAMH and HepG2 cell lines. In some cases, the stereochemically pure drug was more toxic than the E/Z mixtures, but a general statement cannot be made. Our studies show that each stereoisomer could contribute differently to toxicity, suggesting that stereochemical purity issues that could arise from isomerization cannot be ignored.

LRRK2 INHIBITORS

Provided herein are compounds that inhibit or partially inhibit the activity of leucine rich repeat kinases. Also provided herein are methods of treatment of CNS disorders comprising administration of inhibitors of leucine rich repeat kinases.

Synthesis, in silico, in vitro, and in vivo investigation of 5-[ 11C]methoxy-substituted sunitinib, a tyrosine kinase inhibitor of VEGFR-2

Sunitinib (SU11248) is a highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR). Radiolabeled inhibitors of receptor tyrosine kinases (RTKs) might be useful tools for monitoring RTKs levels in tumor tissue giving valuable information for anti-angiogenic therapy. Herein we report the synthesis of 5-methoxy-sunitinib 5 and its 11C-radiolabeled analog [11C]-5. The non-radioactive reference compound 5 was prepared by Knoevenagel condensation of 5-methoxy-2-oxindole with the corresponding substituted 5-formyl-1H-pyrrole. A binding constant (Kd) of 20 nM for 5 was determined by competition binding assay against VEGFR-2. In addition, the binding mode of sunitinib and its 5-methoxy substituted derivative was studied by flexible docking simulations. These studies revealed that the substitution of the fluorine at position 5 of the oxindole scaffold by a methoxy group did not affect the inhibitor orientation, but affected the electrostatic and van der Waals interactions of the ligand with residues near the DFG motif of VEGFR-2. 5-[11C]methoxy-sunitinib ([11C]-5) was synthesized by reaction of the desmethyl precursor with [11C]CH3I in the presence of DMF and NaOH in 17 ± 3% decay-corrected radiochemical yield at a specific activity of 162-205 GBq/μmol (EOS). In vivo stability studies of [11C]-5 in rat blood showed that more than 70% of the injected compound was in blood stream, 60 min after administration.

Regioselective synthesis of heteroaryl triflones by LDA (lithium diisopropylamide)-mediated anionic thia-Fries rearrangement

Novel heteroaryl triflones including oxindole, pyrazolone, pyridine, and quinoline derivatives have been regioselectively synthesized by LDA-mediated thia-Fries rearrangement for the first time. These reactions are also the first examples of the application of anionic thia-Fries rearrangement in heteroaromatic compounds.

Novel Hybrid Compounds

This invention relates to novel hybrid compounds, of formula 1 wherein R1 to R7, L and Y are as defined herein, wherein Y denotes a histone deacetylase inhibiting moiety (such as a heterocycle, hydroxamic acid or diamine) and L denotes a linker group the invention also relates to processes for preparing them and their use as therapeutic agents and diagnostic agents.

INDAZOLYL, BENZIMIDAZOLYL, BENZOTRIAZOLYL SUBSTITUTED INDOLMONE DERIVATIVES AS KINASE INHIBITORS USEFUL IN THE TREATMENT OF CANCER

The present invention is directed to a compound is represented by Structural Formula (A):or a pharmaceutically acceptable salt therof. The present invention is also directed to a pharmaceutical composition comprising a compound represented by Structural Formula (A) described above or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject having cancer, wherein the method comprises administering a therapeutically effective amount of a compound represented by Structural Formula (A) described above or a pharmaceutically acceptable salt thereof.

Introduction of a hydroxy group at the para position and N-iodophenylation of N-arylamides using phenyliodine(III) bis(trifluoroacetate)

The reaction of anilides with phenyliodine(III) bis(trifluoroacetate) (PIFA) in trifluoroacetic acid (TFA), TFA-CHCl3, or hexafluoroisopropyl alcohol (HFIP) is described. When the acyl group of the anilide is highly electronegative, such as trifluoroacetyl, or the phenyl group is substituted with an electron-withdrawing group, the 4-iodophenyl group is transferred from PIFA to the amide nitrogen to afford acetyldiarylamines. On the other hand, when the acyl group contains an electron-donating function, such as 4-methoxyphenyl, or the phenyl group is substituted with an electron-donating group, a trifluoroacetoxy group is transferred to the para position of the anilide aromatic ring. This group is hydrolyzed during workup to produce the corresponding phenol.

Electrophilic Aromatic Substitution with N-Methoxy-N-acylnitrenium Ions Generated from N-Chloro-N-methoxyamides: Syntheses of Nitrogen Heterocyclic Compounds Bearing a N-Methoxyamide Group

N-Methoxy-N-acylnitrenium ions (II), generated by treatment of N-chloro-N-methoxyamides with silver carbonate in trifluoroacetic acid, react with arenes to give N-aryl-N-methoxyamides in good yields.In the case of the intramolecular cyclization of N-chloro-N-methoxy-2-phenylacetamides, the mode of cyclization is highly dependent on the nature of ortho or para substituent groups.Nitrenium ions II can primarily attack three positions (C-1, C-2, and C-6) of a phenyl ring.Normally II attack C-6.On the other hand, when the ortho position was occupied with a substituent group, II attacked both C-2 and C-6, in the former case followed by a 1,2-substituent migration, which was proved by a deuterium labeling experiment.Especially, when a methoxy group is substituted on ortho or para position, II attack C-1 due to the effect of the electron-releasing methoxy group to give spiro dienone compounds 39.A general discussion of the utility and mechanistic details of these reactions is presented.