10242-01-0

Usage

Uses

Used in Pharmaceutical Industry:
5-Methoxy-3-indolecarboxylic acid is used as a key intermediate in the synthesis of various bioactive compounds for pharmaceutical applications. Its ability to be incorporated into complex molecular structures makes it a valuable building block in drug development.
Used in Synthesis of Benzoheterocycle Derivatives:
5-Methoxy-3-indolecarboxylic acid is used as a starting material for the synthesis of benzoheterocycle derivatives. These derivatives have potential applications as vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors. Inhibition of VEGFR-2 is a promising strategy for the treatment of various types of cancer, as it can help to disrupt the formation of new blood vessels that supply tumors with nutrients and oxygen.
Used in Synthesis of Indoleamine 2,3-Dioxygenase 1 Inhibitors:
5-Methoxy-3-indolecarboxylic acid is also used in the synthesis of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. IDO1 is an enzyme involved in the metabolism of tryptophan, an essential amino acid. Overexpression of IDO1 has been linked to the development and progression of certain cancers, making it a potential therapeutic target. Inhibitors of IDO1, synthesized using 5-Methoxy-3-indolecarboxylic acid, may have potential antitumor activity and could be used in the development of novel cancer treatments.

InChI:InChI=1/C10H9NO3/c1-14-6-2-3-9-7(4-6)8(5-11-9)10(12)13/h2-5,11H,1H3,(H,12,13)

Upstream product

• 1006-94-6 5-methoxylindole 
• 1051967-68-0 2,2,2-trifluoro-1-(5-methoxy-1H-indol-3-yl)ethan- 1- one 
• 124-38-9 carbon dioxide 
• 407-25-0 trifluoroacetic anhydride 
• 172595-68-5 methyl 5-methoxy-1H-indole-3-carboxylate 

Downstream Products

• 1396744-20-9 2-(5-methoxy-1H-indole-3-carbonyl)-N-(4-methoxyphenyl)hydrazinecarbothioamide 
• 1396743-86-4 C₁₈H₁₆N₄O₂S 
• 1404532-65-5 {3-[4-(4-butyryl-5-methyl-pyrazol-1-yl)phenylcarbamoyl]-5-methoxy-indol-1-yl}acetic acid methyl ester 
• 1404532-97-3 sodium {3-[4-(4-butyryl-5-methyl-pyrazol-1-yl)phenylcarbamoyl]-5-methoxy-indol-1-yl}acetate 
• 1404536-52-2 [4-(4-butyryl-5-methyl-pyrazol-1-yl)phenyl]-5-methoxy-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide hydrochloride 
• 120-72-9 indole 
• 1006-94-6 5-methoxylindole 
• 172595-68-5 methyl 5-methoxy-1H-indole-3-carboxylate 

Relevant academic research and scientific papers

Design, synthesis, and antitumor activity of novel benzoheterocycle derivatives as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase

The vascular endothelial growth factor receptor-2 signaling pathway promotes the formation of new blood vessels, and vascular endothelial growth factor receptor-2 tyrosine kinase exists in both active and inactive conformations. Novel indole–benzimidazole and indole–benzothiazole derivatives joined by different linkers are designed and synthesized as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase. All the synthesized compounds were evaluated for their cytotoxicity against four human cancer cell lines (HeLa, HT29, A549, and MDA-MB-435) and human umbilical vein endothelial cell. Meanwhile, the inhibitory activities against vascular endothelial growth factor receptor-2 are estimated in vitro and the binding interactions with dual conformations of vascular endothelial growth factor receptor-2 tyrosine kinase are evaluated by molecular docking. Compounds 5a–c and 14 show inhibitory activity against vascular endothelial growth factor receptor-2 tyrosine kinase and promising cytotoxicity, specifically with IC50 values ranging between 0.1 and 1 μM, which imply broad-spectrum antitumor activity. These results provide a deep insight into potential structural modifications for developing potent vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors.

Base-mediated carboxylation of unprotected indole derivatives with carbon dioxide

A simple and straightforward method for the preparation of indole-3-carboxylic acids was discovered through the direct carboxylation of indoles with atmospheric pressure of carbon dioxide (CO2) under basic conditions. The key for the reaction was found to be the use of a large excess of LiOtBu as a base to suppress the undesired decarboxylation side reaction.

METHODS OF TREATING CANCER

The present disclosure relates to methods of treating cancer in a patient using a combination of an inhibitor of an immune checkpoint protein and an indole compound or its phosphate derivative.

Design and synthesis of indoleamine 2,3-dioxygenase 1 inhibitors and evaluation of their use as anti-tumor agents

Indoleamine 2,3-dioxygenase (IDO) 1 is the key enzyme for regulating tryptophan metabolism and is an important target for interrupting tumor immune escape. In this study, we designed four series of compounds as potential IDO1 inhibitors by attaching various fragments or ligands to indole or phenylimidazole scaffolds to improve binding to IDO1. The compounds were synthesized and their inhibitory activities against IDO1 and tryptophan 2,3-dioxygenase were evaluated. The cytotoxicities of the compounds against two tumor cell lines were also determined. Two compounds with a phenylimidazole scaffold (DX-03-12 and DX-03-13) showed potent IDO1 inhibition with IC50 values of 0.3–0.5 μM. These two IDO1 inhibitors showed low cell cytotoxicity, which indicated that they may exert their anti-tumor effect via immune modulation. Compound DX-03-12 was investigated further by determining the in vivo pharmacokinetic profile and anti-tumor efficacy. The pharmacokinetic study revealed that DX-03-12 had satisfactory properties in mice, with rapid absorption, moderate plasma clearance (～36% of hepatic blood flow), acceptable half-life (～4.6 h), and high oral bioavailability (～96%). Daily oral administration of 60 mg/kg of compound DX-03-12 decreased tumor growth by 72.2% after 19 days in a mouse melanoma cell B16-F10 xenograft model compared with the untreated control. Moreover, there was no obvious weight loss in DX-03-12-treated mice. In conclusion, compound DX-03-12 is a potent lead compound for developing IDO1 inhibitors and anti-tumor agents.

INDOLE COMPOUNDS AND THEIR USE

The present disclosure relates to indole compounds and pharmaceutical compositions thereof, and their use in stimulating the immune system of patients in need thereof and in treating cancer.

Tert-Butyl Nitrite-Mediated Synthesis of N-Nitrosoamides, Carboxylic Acids, Benzocoumarins, and Isocoumarins from Amides

This work reports tert-butyl nitrite (TBN) as a multitask reagent for (1) the controlled synthesis of N-nitrosoamide from N-alkyl amides, (2) hydrolysis of N-methoxyamides to carboxylic acids, (3) metal- and oxidant-free benzocoumarin synthesis from ortho-aryl-N-methoxyamides via N-H, C-N, and C-H bond activation, and (4) isocoumarin synthesis using Ru(II)/PEG as a recyclable catalytic system via ortho-C-H activation and TBN as an oxygen source. The sequential functional group interconversion of amide to acid has also been examined using IR spectroscopic analysis. Additionally, this methodology is highly advantageous due to short reaction time, gram scale synthesis, and broad substrate scope.

Efficient Synthesis and Biological Activity of Novel Indole Derivatives as VEGFR-2 Tyrosine Kinase Inhibitors

A series of novel indole derivatives were synthesized as potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase. Among those, compound 10b demonstrated the highest growth inhibition rate of 66.7% against the VEGFR-2 tyrosine kinase at 10 μM which indicates that indole-benzothiazole might be the favorable structure. The binding mode of compound 10b with VEGFR-2 tyrosine kinase was evaluated by molecular docking.

Lithium tert-butoxide-mediated carboxylation reactions of unprotected indoles and pyrroles with carbon dioxide

Unprotected indoles and pyrroles were found to undergo base-mediated carboxylation reactions under ambient pressure of carbon dioxide. It was found that this transition metal-free carboxylation reaction proceeded smoothly with the use of a large excess of LiOtBu.

N -[6-(4-Butanoyl-5-methyl-1 H -pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1 H -indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist

In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.

NOVEL INDOL CARBOXYLIC ACID BISPYRIDYL CARBOXAMIDE DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD AND COMPOSITION CONTAINING THE SAME AS AN ACTIVE INGREDIENT

Disclosed herein are a new indole carboxylic acid bispyridyl carboxamide derivative, a preparation method thereof, and a composition for prevention or treatment of obesity, urinary disorders, and CNS disorders, containing the same as an active ingredient. Because the indole carboxylic acid bispyridyl carboxamide derivatives according to the present invention have high affinity for 5-HT2c receptors, act selectively on the 5-HT2c receptors, the derivatives rarely have adverse effects caused by other receptors. Because the derivatives effectively inhibit serotonin activity, they may be useful for treatment or prevention of obesity; urinary disorders such as urinary incontinence, premature ejaculation, erectile dysfunction, and prostatic hyperplasia; CNS disorders such as depression, anxiety, concern, panic disorder, epilepsy, obsessive-compulsive disorder, migraine, sleep disorder, withdrawal from drug abuse, Alzheimer's disease, and schizophrenia, associated with 5-HT2c receptors.