19017-52-8

Usage

Uses

Used in Medicinal Chemistry:
(5-CHLORO-2-METHYL-1H-INDOL-3-YL)-ACETIC ACID is used as a research compound for its potential applications in medicinal chemistry. Its structural similarity to the natural hormone IAA allows it to interact with biological systems, providing a basis for the development of new therapeutic agents.
Used in Agriculture:
In the agricultural industry, (5-CHLORO-2-METHYL-1H-INDOL-3-YL)-ACETIC ACID is used as a synthetic plant growth regulator. It mimics the actions of IAA, which can enhance plant growth and development, potentially leading to improved crop yields and quality.
Used in Cancer Treatment Research:
(5-CHLORO-2-METHYL-1H-INDOL-3-YL)-ACETIC ACID is used as a potential therapeutic agent in cancer treatment research. Its ability to interact with biological systems suggests that it may have applications in targeting and treating cancer cells, offering a new avenue for the development of cancer therapies.
Used in Anti-Inflammatory Research:
In the field of anti-inflammatory research, (5-CHLORO-2-METHYL-1H-INDOL-3-YL)-ACETIC ACID is used as a compound of interest. Its potential to modulate inflammatory responses could lead to the development of new treatments for inflammatory diseases and conditions.

InChI:InChI=1/C11H10ClNO2/c1-6-8(5-11(14)15)9-4-7(12)2-3-10(9)13-6/h2-4,13H,5H2,1H3,(H,14,15)

Upstream product

• 1073-70-7 4-chlorophenylhydrazine hydrochloride 
• 123-76-2 levulinic acid 
• 172595-66-3 methyl 2-(5-chloro-2-methyl-1H-indol-3-yl)acetate 
• 1075-35-0 5-chloro-2-methylindole 
• 539-88-8 4-oxopentanoic acid ethyl ester 
• 3446-72-8 5-chloro-2-methyl-1H-indole-3-acetic acid ethyl ester 
• 57335-86-1 5-Chloro-2-methyl-1H-indole-3-carboxaldehyde 
• 33577-16-1 methyl methylsulfinylmethyl sulfide 

Downstream Products

• 3446-72-8 5-chloro-2-methyl-1H-indole-3-acetic acid ethyl ester 
• 1297276-86-8 2-(3-((3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-5-chloro-2-methyl-1H-indol-1-yl)acetic acid 
• 1297284-49-1 2-benzyl-4-((5-chloro-2-methyl-1H-indol-3-yl)methyl)-phthalazin-1(2H)-one 
• 1297284-50-4 methyl 2-(3-((3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-methyl)-5-chloro-2-methyl-1H-indol-1-yl)acetate 
• 1297284-47-9 2-(2-(5-chloro-2-methyl-1H-indol-3-yl)acetyl)benzoic acid 

Relevant academic research and scientific papers

Indole compounds with: N-ethyl morpholine moieties as CB2 receptor agonists for anti-inflammatory management of pain: Synthesis and biological evaluation

The CB2 receptor plays a crucial role in analgesia and anti-inflammation. To develop novel CB2 agonists with high efficacy and selectivity, a series of indole derivatives with N-ethyl morpholine moieties (compounds 1-56) were designed, synthesized and biologically evaluated. Compounds 1, 2, 3, 46 and 53 exhibited high CB2 receptor affinity at low nanomolar concentrations and good receptor selectivity (EC50(CB1)/EC50(CB2) greater than 1000). The most active compound, compound 2, was more potent than the standard drug GW405833 for in vitro agonistic action on the CB2 receptor. More importantly, in a rat model for CFA-induced inflammatory hyperalgesia, compound 2 had a potent anti-inflammatory pain effect within 12 hours after administration. At the 1 h time point, compound 2 had a dose-dependent reversal for hyperalgesia with an estimated ED50 value of 1.097 mg kg-1. Moreover, compound 2 significantly suppressed the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in CFA-induced lesions. These protective effects of compound 2 on inflammatory pain were superior to those of GW405833, suggesting that compound 2 may be a promising therapeutic drug that needs further validation.

Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity

Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity-based probe, could be used to pull down active endogenous KLK6.

Diazine indole acetic acids as potent, selective, and orally bioavailable antagonists of chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2) for the treatment of allergic inflammatory diseases

New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic acids, are described. The initial hit 1 had good potency but poor permeability, metabolic stability, and PK. Initial optimization led to compounds of type 2 with low oxidative metabolism but poor oral bioavailability. Poor permeability was identified as a liability for these compounds. Addition of a linker between the indole and diazine moieties afforded a series with good potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents. 32 was identified as the development track candidate. It was potent in cell based, binding, and whole blood assays and exhibited good PK profile. It was efficacious in mouse models of contact hypersensitivity (1 mg/kg b.i.d.) and house dust (20 mg/kg q.d.) when dosed orally. In sheep asthma, administration at 1 mg/kg iv completely blocked the LAR and AHR and attenuated the EAR phase.

INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS

Disclosed are compounds of Formula (I): which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.

Discovery of selective indole-based prostaglandin D2 receptor antagonist

A series of N-benzoyl-2-methylindole-3-acetic acids were synthesized and biologically evaluated as prostaglandin (PG) D2 receptor antagonists. Some of the selected compounds significantly inhibited OVA-induced vascular permeability in guinea pig conjunctiva after oral dosing. Structure-activity relationship study is presented.

Compounds exhibiting thrombopoietin-like activities

The compounds of the invention are compounds represented by the following general formula (1): wherein E represents one selected from the group consisting of a methylidyne group and a nitrilo group, R1 represents one selected from the group consisting of optionally substituted aryl groups and optionally substituted heteroaryl groups, R2 represents one selected from the group consisting of a hydrogen atom and alkyl groups, W1 represents an amino acid residue, A represents one selected from the group consisting of a carbonyl group and a sulfonyl group, X1 represents one selected from the group consisting of optionally substituted alkylene groups and optionally substituted alkenylene groups, and p represents 0 or 1; and their pharmacologically acceptable salts, which exhibit thrombopoietin-like activity.

New N-(pyridin-4-yl)-(indol-3-yl)acetamides and propanamides as antiallergic agents

A series of new N-(pyridin-4-yl)-(indol-3-yl)alkylamides 44-84 has been prepared in the search of novel antiallergic compounds. Synthesis of the desired ethyl (2-methyindol-3-yl)acetates 1-4 was achieved by indolization under Fischer conditions; Japp-Klingemann method followed by 2- decarboxylation afforded the ethyl (indol-3-yl)alkanoates 17-25. Amidification was successfully carried out by condensation of the corresponding acids or their N-aryl(methyl) derivatives with 4-aminopyridine promoted by 2-chloro-1-methylpyridinium iodide. Efforts to improve the antiallergic potency of the title series by variation of the indole substituents (R1, R2, R) and the length of the alkanoic chain (n = 1, 2, 3) led to the selection of N-(pyridin-4-yl)-[1-(4-fluorobenzyl)indol-3- yl]acetamide 45, out of 41 compounds. This amide was 406-fold more potent than astemizole in the ovalbumin-induced histamine release assay, using guinea pig peritoneal mast cells, with an IC50 = 0.016 μM. Its inhibitory activity in IL-4 production test from Th-2 cells was identical to that of the reference histamine antagonist (IC50 = 8.0 μM) and twice higher in IL-5 assay: IC50 = 1.5 and 3.3 μM, respectively. In vivo antiallergic activity evaluation confirmed efficiency of 45 in sensitized guinea pig late phase eosinophilia inhibition, after parenteral and oral administration at 5 and 30 mg/kg, respectively. Its efficiency in inhibition of microvascular permeability was assessed in two rhinitis models; ovalbumin and capsaicin- induced rhinorrhea could be prevented after topical application of submicromolar concentrations of 45 (IC50 = 0.25 and 0.30 μM); and it also exerted significant inhibitory effect in the first test after iv and oral administration, with ID50 = 0.005 and 0.46 mg/kg.