1010-68-0

Usage

Uses

Used in Pharmaceutical Industry:
1,3-Dihydro-5-hydroxy-1,3-dimethyl-2H-indol-2-one is used as a therapeutic agent for the treatment of neurodegenerative diseases and neurological disorders. Its pharmacological properties, including enzymatic inhibition, contribute to its potential efficacy in managing these conditions.
Used in Medicinal Chemistry Research:
1,3-Dihydro-5-hydroxy-1,3-dimethyl-2H-indol-2-one is utilized as a subject of interest in medicinal chemistry for its antioxidant and anti-inflammatory properties. These characteristics make it a promising candidate for the development of new drugs targeting a range of health issues where oxidative stress and inflammation are implicated.

Upstream product

• 3154-18-5 N-methyl-p-phenetidine 
• 563-76-8 α-bromopropionyl bromide 
• 5961-59-1 N-methyl-N-(4-methoxyphenyl)amine 
• 150-75-4 N-methyl-p-aminophenol 
• 153880-70-7 2-bromo-N-(4-ethoxy-phenyl)-N-methyl-propionamide 
• 161986-95-4 4-hydroxy-N-methyl-N-(α-bromopropionyl)aniline 
• 153880-69-4 N-(4-methoxyphenyl)-N-methyl-2-bromopropionylamide 

Downstream Products

• 155795-39-4 (3S,1'S)-N-methyl-N-(1'-phenylethyl)-1,3-dimethyl-5-methoxyoxindol-3-ilacetamide 
• 65166-97-4 (-)-esermethole 
• 57-47-6 (+/-)-Physostigmine 
• 159652-56-9 (+)-(3aR)-N¹-benzylnoreseroline phenylcarbamate 
• 164455-08-7 (+)-(3aR)-N¹-benzylnoreseromethole 
• 116707-99-4 1,3-dimethyl-5-methoxyindolin-2-one 
• 131057-63-1 1,3-dimethyl-5-ethoxyoxindole 

Relevant academic research and scientific papers

Agents useful for reducing amyloid precursor protein and treating demantia and methods of use thereof

The present invention provides compounds and methods of administering compounds to a subject taht can reduce βAPP production and that is not toxic in a wide range of dosages. The present invention also provides non-carbamate compounds and methods of administering such compounds to a subject that can reduce βAPP production and that is not tocix in a wide range of dosages. It has been discovered that either the racemic or enantiomerically pure non-carbamate compounds can be used to decrease βAPP production.

Racemic N1-norphenserine and its enantiomers: Unpredicted inhibition of human acetyl- and butyrylcholinesterase and β-amyloid precursor protein in vitro

The optically pure enantiomers of N1-norphenserine (15, 16) were synthesized and its racemate 17 was prepared by mixing equal parts of each enantiomer. (-)-N1-Norphenserine (15) was prepared by partial synthesis initiated from the natural product, (-)-physostigmine (1). (+)-N 1-Norphenserine (16) was prepared by total synthesis using the Julian oxindole route, with modifications. The in vitro inhibitory activities of 15-17 were quantified against human erythrocyte AChE and plasma BChE as well as against human neuroblastoma cell β-amyloid precursor protein secretion in cell culture. All were active. Racemic compound (17) with a high AChE and β-amyloid precursor protein inhibitory action may warrant further assessment in Alzheimer's disease models.

Process for preparing 1,3-dialkyl-5-hydroxyoxindoles and the ether derivatives thereof

The invention is directed to a process for preparing a 1,3-dialkyl-5-hydroxyoxindole of formula 1: STR1 comprising heating an N-alkyl-p-alkoxy-(α-haloacyl)anilide of formula 2: STR2 wherein the substituents are as defined herein, in the presence of an anhydrous zinc halide to a temperature in the range from about 120° C. to about 160° C., and isolating the 1,3-dialkyl-5-hydroxyoxindole prepared.

Process for the Preparation of Eserethole

Eserethole of formula STR1 is prepared from 1,3-dimethyl-5-hydroxy-oxindole compound II which is acylated in the first step to obtain 1,3-dimethyl-5-acyloxyoxindole (III). The product is reacted with chloroacetonitrile to obtain 1,3-dimethyl-3-cyanomethyl-5-acyloxy-oxindole (IV). The 5-acyloxy group is hydrolyzed and the hydroxy group is ethoxylated with ethyl halides or sulfate. Then the product is cyclized by treatment with sodium bis-(methoxy-ethoxy)aluminum hydride, to give O-ethyl-nor-eseroline (VI) and the compound is methylated to give eserethole (VII).

New asymmetric synthesis of (-)-esermethole

A new synthesis of (-)-esermethole, based on the asymmetric alkylation at C(3) of racemic 1,3-dimethyl-5-methoxyoxindole (3), is described. The chloroacetyl derivatives of (-)-menthol and (S)-N-methyl-(1-phenylethyl) amine were chosen as chiral alkylating agents and used under different reaction conditions (temperature, solvent and base). In particular, the latter reacted with 3 in toluene at 10°C, in the presence of t-butyllitium, giving (3S,1'S)-N-methyl-N-(1'-phenylethyl)-1,3-dimethyl-5-methoxyoxindol-3-i lacetamide (10) with a 63% d.e.. This intermediate was easily separated from the undesired minor (3R,1'S) diastereomer (11) and converted to (-)-esermethole (99.6% e.e.) in two steps.

TOTAL SYNTHESIS OF RACEMIC PHYSOSTIGMINE, PHYSOVENINE AND ITS SULFUR ANALOGUE BY THE OXINDOLE-5-O-TETRAHYDROPYRANYL ETHER ROUTE

1,3-Dimethyl-5-tetrahydropyranyloxyoxindole (4) was synthesized from 4-methylaminophenol sulfate (metol) (1).Phase transfer catalyzed C3-alkylation of compound (4) produced alcohol (5), nitrile (8), and thioalkohol (13) after treatment of bromide (12) with thiourea.Compound (5) and (13) were converted into racemic physovenine (7) and thiaphysovenine (15) by reaction with LAH, in situ deprotection, and reaction of phenols with methyl isocyanate.Conversion of nitrile (8) into racemic physostigmine (11) which included a reductive N-methylation of 9 was similarly accomplished.