2878-86-6

Usage

Indole group

A five-membered aromatic ring system with a nitrogen atom at position 1, contributing to the compound's aromaticity and potential binding properties.

Acetamide group

A carbonyl group (C=O) bonded to a nitrogen atom in a tetrahedral geometry, providing hydrogen bonding ability and potential for coordination with other molecules.

4-chlorobenzoyl group

A benzoyl group (C=O) with a chlorine atom at the para position, contributing to the compound's lipophilicity and potential electrophilic reactivity.

2-hydroxyethyl group

An ethyl group with a hydroxyl group, providing hydrogen bonding ability and increasing the compound's solubility in polar solvents.

Aromaticity

The presence of the indole group and the benzoyl group contributes to the compound's aromaticity, which can affect its reactivity and biological activity.

Hydrogen bonding

The presence of the amide and hydroxyl groups allows for hydrogen bonding, which can affect the compound's solubility and interactions with other molecules.

Lipophilicity

The presence of the 4-chlorobenzoyl group increases the compound's lipophilicity, which can affect its ability to cross cell membranes and interact with hydrophobic targets.

Electrophilicity

The presence of the 4-chlorobenzoyl group and the carbonyl groups makes the compound potentially electrophilic, which can affect its reactivity with nucleophiles.

Steric hindrance

The presence of the methoxy and methyl groups can contribute to steric hindrance, which can affect the compound's reactivity and interactions with other molecules.

Upstream product

• 53-86-1 [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid 
• 141-43-5 ethanolamine 

Downstream Products

• 960214-87-3 C₄₇H₄₅ClN₂O₁₄ 
• 167986-22-3 indomethacin-ethanolamide-palmitate 

Relevant academic research and scientific papers

Synthesis, characterization, and cellular investigations of porphyrin- And chlorin-indomethacin conjugates for photodynamic therapy of cancer

Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) with a strong selective inhibitor activity towards cyclooxygenase-2 (COX-2), an enzyme that is highly overexpressed in various tumour cells, being involved in tumourigenesis. Concomitantly, porphyrins have gained much attention as promising photosensitizers (PSs) for the non-invasive photodynamic therapy (PDT) of cancer. Herein, we report the design, and determine the singlet oxygen generation capacity andin vitrocellular toxicity of porphyrin- and chlorin-indomethacin conjugates (P2-IndandC2-Ind). Both the conjugates were obtained in high yields and were characterized by1H,19F and13C NMR as well as by high resolution mass spectrometry. The singlet oxygen generation properties were assessed by the 1,3-diphenylisobenzofuran singlet oxygen trap method, which showed thatC2andC2-Indare the best singlet oxygen photosensitizers. In addition, it was found that the presence of indomethacin did not influence the singlet oxygen generation of porphyrin or chlorin. Cytotoxicity studies of the conjugate in human HEp2 cells revealed that the porphyrin- and chlorin-indomethacin conjugates have similar dark cytotoxicities, while chlorinC2was shown to be the most phototoxic. Despite having lower cellular uptake thanC2-Indafter 24 hours, chlorinC2had a broad localization in HEp2 cells while the chlorin-indomethacin conjugateC2-Indcould be detected in the form of small aggregates. DFT calculations were performed to shed light on the reaction energy involved in the formation of the indomethacin conjugates and to compare the relative stability of selected isomers in solution. Moreover, the calculated energy of their first excited triplet state structures confirmed their use as suitable photosensitizers to generate singlet oxygen for PDT.

Podophyllotoxin analogues active versus Trypanosoma brucei

In an effort to discover novel anti-trypanosomal compounds, a series of podophyllotoxin analogues coupled to non-steroidal anti-inflammatory drugs (NSAIDs) has been synthesized and evaluated for activity versus Trypanosoma brucei and a panel of human cell lines, revealing compounds with low nano-molar potencies. It was discovered that coupling of NSAIDs to podophyllotoxin increased the potencies of both compounds over 1300-fold. The compounds were shown to be cytostatic in nature and seem to act via de-polymerization of tubulin in a manner consistent with the known activities of podophyllotoxin. The potencies against T. brucei correlated directly with Log P values of the compounds, suggesting that the conjugates are acting as hydrophobic tags allowing podophyllotoxin to enter the cell.

Synthesis of COX-2 and FAAH inhibitors

Methods for preparing indoles that are useful COX-2 inhibitors and intermediates useful in such methods are described.

Therapeutic compound-fatty acid conjugates

The present invention provides therapeutic conjugates which comprise a therapeutic compound bound to one to three acyl groups derived from fatty acids. The therapeutic compounds are preferably non-steroidal anti-infiammatory agents which include a carboxylic acid group. The compounds involve the use of tromethamine or ethanolamine derivative to link the acyl groups derived from fatty acids to the therapeutic compounds.

Ester and amide derivatives of the nonsteroidal antiinflammatory drug, indomethacin, as selective cyclooxygenase-2 inhibitors

Recent studies from our laboratory have shown that derivatization of the carboxylate moiety in substrate analogue inhibitors, such as 5,8,11,14- eicosatetraynoic acid, and in nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin and meclofenamic acid, results in the generation of potent and selective cyclooxygenase-2 (COX-2) inhibitors (Kalgutkar et al. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 925-930). This paper summarizes details of the structure-activity studies involved in the transformation of the arylacetic acid NSAID, indomethacin, into a COX-2-selective inhibitor. Many of the structurally diverse indomethacin esters and amides inhibited purified human COX-2 with IC50 values in the low-nanomolar range but did not inhibit ovine COX-1 activity at concentrations as high as 66 μM. Primary and secondary amide analogues of indomethacin were more potent as COX-2 inhibitors than the corresponding tertiary amides. Replacement of the 4- chlorobenzoyl group in indomethacin esters or amides with the 4-bromobenzyl functionality or hydrogen afforded inactive compounds. Likewise, exchanging the 2-methyl group on the indole ring in the ester and amide series with a hydrogen also generated inactive compounds. Inhibition kinetics revealed that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Conversion of indomethacin into ester and amide derivatives provides a facile strategy for generating highly selective COX-2 inhibitors and eliminating the gastrointestinal side effects of the parent compound.