153435-96-2

Usage

Uses

Used in Pharmaceutical Industry:
ETHYL 4,6-DICHLORO-3-FORMYL-1H-INDOLE-2-CARBOXYLATE is used as a reactant for the preparation of 3-[2-(3-aminophenyl)-2-carboxyvinyl]-4,6-dichloro-1H-indole-2-carboxylic acid. ETHYL 4,6-DICHLORO-3-FORMYL-1H-INDOLE-2-CARBOXYLATE serves as a selective glycine-site N-methyl-D-aspartate (NMDA) receptor antagonist, which is crucial in the development of medications targeting various neurological disorders and conditions related to the overstimulation of NMDA receptors.
The application of ETHYL 4,6-DICHLORO-3-FORMYL-1H-INDOLE-2-CARBOXYLATE in the pharmaceutical industry is primarily due to its role in the synthesis of NMDA receptor antagonists, which have potential therapeutic benefits in treating conditions such as Alzheimer's disease, Parkinson's disease, chronic pain, and other neurological disorders.

InChI:InChI=1/C12H9Cl2NO3/c1-2-18-12(17)11-7(5-16)10-8(14)3-6(13)4-9(10)15-11/h3-5,15H,2H2,1H3

Upstream product

• 626-43-7 3,5-Dichloroaniline 
• 137836-38-5 (E)-ethyl 2-(2-(3,5-dichlorophenyl)hydrazono)propanoate 
• 39943-56-1 3,5-dichlorophenylhydrazine 
• 63352-99-8 (3,5-dichlorophenyl)hydrazine hydrochloride 
• 103855-01-2 ethyl 2-[2-(3,5-dichlorophenyl)hydrazinylidene]propanoate 
• 53995-82-7 4,6-dichloro-indole-2-carboxylic acid,ethyl ester 
• 68-12-2 N,N-dimethyl-formamide 
• 93-61-8 N-methyl-N-phenylformamide 

Downstream Products

• 1026289-06-4 4,6-dichloro-3-(2-cyclohexyl-1-hydroxy-2-methoxycarbonyl-ethyl)-1H-indole-2-carboxylic acid ethyl ester 
• 179106-92-4 4,6-dichloro-3-formyl-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl ester 
• 179106-66-2 (Z)-2-(phenyl)-3-(2-carboethoxy-4,6-dichloroindol-3-yl)-propenonitrile 
• 496956-01-5 4,6-dichloro-3-{[3-(3,5-dichlorophenyl)-2,4-dioxo-1-imidazolidinyl]methyl}indole-2-carboxylic acid ethyl ester 
• 496955-94-3 4,6-dichloro-3-{[(cyclohexylaminocarbonyl)(2-methoxy-2-oxoethyl)amino]methyl}indole-2-carboxylic acid ethyl ester 
• 496956-07-1 4,6-dichloro-3-{[3-(3-acetylphenyl)-2,4-dioxo-1-imidazolidinyl]methyl}indole-2-carboxylic acid ethyl ester 
• 496956-06-0 4,6-dichloro-3-{[3-(4-acetylphenyl)-2,4-dioxo-1-imidazolidinyl]methyl}indole-2-carboxylic acid ethyl ester 
• 205646-84-0 ethyl (Z)-4,6-dichloro-3-[2-cyano-2-(3-nitrophenyl)-ethenyl]-1H-indole-2-carboxylate 
• 496956-05-9 4,6-dichloro-3-{[3-(4-methoxyphenyl)-2,4-dioxo-1-imidazolidinyl]methyl}indole-2-carboxylic acid ethyl ester 
• 496956-10-6 (S)-4,6-dichloro-3-[(5-isopropyl-2,4-dioxo-3-phenyl-1-imidazolidinyl)methyl]indole-2-carboxylic acid ethyl ester 
• 496956-08-2 (S)-4,6-dichloro-3-[(5-methyl-2,4-dioxo-3-phenyl-1-imidazolidinyl)methyl]indole-2-carboxylic acid ethyl ester 
• 496956-09-3 (R)-4,6-dichloro-3-[(5-methyl-2,4-dioxo-3-phenyl-1-imidazolidinyl)methyl]indole-2-carboxylic acid ethyl ester 
• 496955-91-0 3-{[(anilinocarbonyl)(2-hydroxyethyl)amino]methyl}-4,6-dichloroindole-2-carboxylic acid ethyl ester 
• 496955-95-4 4,6-dichloro-3-[(2,4-dioxo-3-phenyl-1-imidazolidinyl)methyl]indole-2-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

Development of [3H]2-carboxy-4,6-dichloro-1 H -indole-3-propionic acid ([3H]PSB-12150): A useful tool for studying GPR17

The recently described synthetic GPR17 agonist 2-carboxy-4,6-dichloro-1H- indole-3-propionic acid (1) was prepared in tritium-labeled form by catalytic hydrogenation of the corresponding propenoic acid derivative 8 with tritium gas. The radioligand [3H]PSB-12150 (9) was obtained with a specific activity of 17 Ci/mmol (629 GBq/mmol). It showed specific and saturable binding to a single binding site in membrane preparations from Chinese hamster ovary cells recombinantly expressing the human GPR17. A competition assay procedure was established, which allows the determination of ligand binding affinities.

Discovery of 3-Substituted 1H-Indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT1 Selective Antagonists

The indole derivative, 3-((E)-3-((3-((E)-2-(7-chloroquinolin-2yl)vinyl)phenyl)amino)-3-oxoprop-1-en-1-yl)-7-methoxy-1H-indole-2-carboxylic acid (17k), was identified as a novel and highly potent and selective CysLT1 antagonist with IC50 values of 0.0059 ± 0.0011 and 15 ± 4 μM for CysLT1 and CysLT2, respectively.

Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the N-methyl- d -aspartate receptor

The N-methyl- d-aspartate (NMDA) receptor as a type of ionotropic glutamatergic receptors is essential for physiological processes such as learning, memory and synaptic plasticity. A glutamate-induced overactivation of these receptors, accompanied by increased intracellular calcium concentration, causes cell injury and leads to a large number of acute or chronic neurological disorders, such as stroke, trauma, Parkinson's disease and Alzheimer's disease. In an attempt to visualise the glutamatergic neurotransmission in vivo with positron emission tomography, novel fluoroethoxy- and methoxy-substituted reference compounds based on the lead structure of a hydantoin-substituted indole-2-carboxylic acid were synthesised. The affinities towards the glycine binding site of the NMDA receptor showed Ki values between 322 and 11 nM and the lipophilicities ranged from logD values of 1.51 to 2.53. On the basis of these results, precursor compounds were synthesised containing a phenolic hydroxy moiety to obtain the radiolabelled ligands through an alkylation reaction. Radiosynthesis was achieved by labelling the precursor ethyl 4,6-dichloro-3-((3-(4-hydroxyphenyl)-2,4-dioxoimidazolidin-1-yl)methyl)- indole-2-carboxylate with 2-[18F]fluoroethyl tosylate or [ 11C]methyl iodide and subsequent cleavage of the ethyl ester moiety. This gave the final products in overall decay-corrected radiochemical yields of 5-7% and 6-9% and specific activities of 24-67 GBq/μmol and 8-26 GBq/μmol, respectively. Copyright

CoMFA, synthesis, and pharmacological evaluation of (E)-3-(2-carboxy-2- arylvinyl)-4,6-dichloro-1H-indole-2-carboxylic acids: 3-[2-(3-Aminophenyl)-2- carboxyvinyl]-4,6-dichloro-1H-indole-2-carboxylic acid, a potent selective glycine-site NMDA receptor antagonist

(E)-3-(2-Carboxy-2-phenylvinyl)-4,6-dichloro-1H-indole-2-carboxylic acid, 1, is a potent and selective antagonist of the glycine site of the N-methyl-D-aspartate (NMDA) receptor. Using 3D comparative molecular field analysis (CoMFA) to guide the synthetic effort, a series of aryl diacid analogues of 1 were synthesized to optimize in vivo potency, duration of action, and binding activity. It was found that the incorporation of a substituted aromatic with an electron withdrawing group or a heterocyclic group at the 2-position of the 3-propenyl moiety of 1 gave compounds with better affinity and potency in the murine stroke model. Ultimately this led to the discovery of 3-[2-(3-aminophenyl)-2-carboxyvinyl]-4,6-dichloro-1H-indole-2-carboxylic acid, 19, as a new potent selective glycine-site NMDA receptor antagonist.

NMDA (N-METHYL-D-ASPARTATE) ANTAGONISTS

The present invention is new excitatory amino acid antagonists (herein referred to as compounds of formula (1)). These new antagonists are useful as NMDA (N-methyl-D-aspartate) antagonists.

Synthesis of (E)-3-(2-carboxy-2-pyridyl-vinyl)-4,6-dichloro-1H-indole-2-carboxylic acids, glycine-site NMDA receptor antagonists, utilizing the Knoevenagel condensation reaction

The Knoevenagel condensation of arylacetonitriles with ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate (2), followed by hydrolysis, provides a convenient entry into a series of analogs of MDL 105,519, 1, a selective glycine site N-methyl-D-aspartate (

Chemical development of MDL 103371: An N-methyl-D-aspartate-type glycine receptor antagonist for the treatment of stroke

MDL 103371 is a N-methyl-D-aspartate (NMDA)-type glycine receptor antagonist for the potential treatment of stroke. Evaluation of five different synthetic routes, which included Stille, Suzuki, enol ether, Knoevenagel, and the Mukaiyama coupling reactions

Substituted indole-2-carboxylates as in vivo potent antagonists acting as the strychnine-insensitive glycine binding site

A series of indole-2-carboxylates bearing suitable chains at the C-3 position of the indole nucleus was synthesized and evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions ind

3-(indol-3-yl)-propenoic acid derivatives and pharmaceutical compositions thereof

The present invention is new 3-(indol-3-yl)-propenoic acid derivatives and pharmaceutical compositions thereof. These new 3-indolyl-3-yl-prpopenoic acid derivatives are useful as NMDA antagonist.