55654-68-7

Usage

Type of compound

chemical compound used as an intermediate in the synthesis of pharmaceuticals and agrochemicals

Derivative

1H-indole-3-acetic acid, a naturally occurring plant hormone

Reactive group

acetyl group with a chlorine atom

Functional group

α-oxo-1-(phenylmethyl) group

Reactivity

enhanced reactivity due to the presence of the α-oxo-1-(phenylmethyl) group

Potential applications

drug development and agrochemical production.

Upstream product

• 79-37-8 oxalyl dichloride 
• 3377-71-7 N-benzylindole 
• 120-72-9 indole 
• 100-44-7 benzyl chloride 

Downstream Products

• 108977-91-9 2-(1-benzyl-1H-indol-3-yl)-2-oxoacetamide 
• 128760-90-7 3-(1-Benzyl-1H-indol-3-yl)-4-(1-methyl-1H-indol-3-yl)-furan-2,5-dione 
• 1169700-36-0 1-(1-benzyl-1H-indol-3-yl)-4-methoxybut-2-yn-1-one 
• 1169700-38-2 1-(1-benzyl-1H-indol-3-yl)-3-(trimethylsilyl)prop-2-yn-1-one 
• 1289675-76-8 1-(1-benzyl-1H-indol-3-yl)oct-3-yne-1,2-dione 
• 1403815-55-3 C₂₉H₂₂N₂O₃ 
• 1489263-00-4 2-(1-benzyl-1H-indole-3-yl)-2-oxo-N-phenylacetamide 

Relevant academic research and scientific papers

Anti-leukemic properties of aplysinopsin derivative ee-84 alone and combined to bh3 mimetic a-1210477

Aplysinopsins are a class of marine indole alkaloids that exhibit a wide range of biological activities. Although both the indole and N-benzyl moieties of aplysinopsins are known to possess antiproliferative activity against cancer cells, their mechanism of action remains unclear. Through in vitro and in vivo proliferation and viability screening of newly synthesized aplysinopsin analogs on myelogenous leukemia cell lines and zebrafish toxicity tests, as well as analysis of differential toxicity in noncancerous RPMI 1788 cells and PBMCs, we identified EE-84 as a promising novel drug candidate against chronic myeloid leukemia. This indole derivative demonstrated drug-likeness in agreement with Lipinski’s rule of five. Furthermore, EE-84 induced a senescent-like phenotype in K562 cells in line with its cytostatic effect. EE-84-treated K562 cells underwent morphological changes in line with mitochondrial dysfunction concomitant with autophagy and ER stress induction. Finally, we demonstrated the synergistic cytotoxic effect of EE-84 with a BH3 mimetic, the Mcl-1 inhibitor A-1210477, against imatinib-sensitive and resistant K562 cells, highlighting the inhibition of antiapoptotic Bcl-2 proteins as a promising novel senolytic approach against chronic myeloid leukemia.

Design, synthesis, biological evaluation and molecular modelling studies of conophylline inspired novel indolyl oxoacetamides as potent pancreatic lipase inhibitors

A novel series of 21 indolyl oxoacetamide analogues was designed based on the natural product lead conophylline, and evaluated for their pancreatic lipase inhibitory activity using porcine pancreatic lipase (Type II). Analogues 12c and 12b exhibited comparatively greater potential (IC50 values of 2.95 and 3.26 μM) than conophylline (IC50-3.31 μM), while the standard drug, orlistat, exhibited a potent IC50 value of 0.99 μM. Further, analogues 12b and 12c exhibited reversible competitive inhibition similar to orlistat and conophylline, and possessed Ki values of 1.89 and 1.69 μM, respectively. Molecular docking of these analogues was in agreement with the in vitro results, wherein the MolDock scores exhibited significant correlation with their inhibitory activity. A 10 ns molecular dynamics simulation of 12c complexed with pancreatic lipase confirmed the role of extended alkyl interactions, along with π-π stacking and π-cation interactions, in stabilising the ligand in the active site (maximum observed RMSD ≈ 3.5 ?). ADMET prediction indicated the GI absorption of these analogues to be high; however, they did not possess carcinogenicity and hepatotoxicity in contrast to orlistat and conophylline.

Design, synthesis, biological evaluation and molecular modelling studies of indole glyoxylamides as a new class of potential pancreatic lipase inhibitors

A series of eighteen indole glyoxylamide analogues were synthesized, characterized and evaluated for their pancreatic lipase inhibitory activity. Porcine pancreatic lipase (Type II) was used with 4-nitrophenyl butyrate (as substrate) for the in vitro assay. Compound 8f exhibited competitive inhibition against pancreatic lipase with IC50 value of 4.92 μM, comparable to that of the standard drug, orlistat (IC50 = 0.99 μM). Compounds 7a-i and 8a-i were subjected to molecular docking into the active site of human PL (PDB ID: 1LPB) wherein compound 8f possessed a potential MolDock score of ?153.037 kcal/mol. Molecular dynamics simulation of 8f complexed with pancreatic lipase, confirmed the role of aromatic substitution in stabilizing the ligand through hydrophobic interactions (maximum observed RMSD = 3.5 ?).

Anti HIV-1 agents 6. Synthesis and anti-HIV-1 activity of indolyl glyoxamides

In order to discover compounds with superior anti-human immunodeficiency virus type 1 (HIV-1) activity, 9 new indolyl glyoxamide derivatives (3a-i) were synthesized and preliminarily evaluated as HIV-1 inhibitors in vitro. Among all the derivatives, espec

Three-component synthesis of ynediones by a glyoxylation/ Stephens-Castro coupling sequence

(Chemical Equation Presented) One step back, two steps forward! Starting from diverse heterocycles, the title reaction furnishes ynediones under very mild conditions in a direct and preparatively simple one-pot process. The key to avoiding decarbonylation

Consecutive three-component synthesis of ynones by decarbonylative sonogashira coupling

A study was conducted to demonstrate consecutive three-component synthesis of ynones by decarbonylative Sonogashira coupling. Sonogashira coupling started from electron-rich heterocycles and oxalyl chloride as a source of the CO building block via interme

2-(1h-indol-3-yl)-2-oxo-acetic acid amides with antitumor activity

2-(III-Indol-3-yl)-2-oxo-acetamide derivatives of formula (I) having antitumor activity in particular against solid tumors, specifically colon and lung tumors.

Indole amide derivatives: Synthesis, structure-activity relationships and molecular modelling studies of a new series of histamine H1-receptor antagonists

A number of indole amide derivatives bearing a basic side chain, in which the indole ring replaces the isoster benzimidazole nucleus typical of some well-known antihistamines, were prepared and tested for their H1- antihistaminic activity. The 1-benzyl-3-indolecarboxamides 32-42 showed antihistaminic (H1) activity (pA2 6-8); the 3-indolylglyoxylylamides 7-16 and the 2-indolecarboxamides 48-56 showed little or no activity. Insertion of the basic side chain of the active 3-indolecarboxamide derivatives into a piperazine ring (compounds 57-59) led to a dramatic loss of activity. All the active compounds proved to be competitive antagonists, since the values of the regression slope were not statistically different from 1. The most active compounds, 32, 33, 38-41, were also tested both in vitro for their anticholinergic activity and in vivo for their ability to antagonize histamine-induced cutaneous vascular permeability in rats. The biological results and the structure-activity relationships of the novel compounds are discussed in the light of molecular modelling studies, taking the molecule of astemizole as a model, and referring to proposed H1-receptor pharmacophore models.

A convenient synthesis of bisindolyl- and indolylaryl maleic anhydrides

The reaction of indolyl-3-glyoxylyl chlorides, easily prepared from the corresponding indoles, with arylacetic acids provides indolylaryl maleic anhydrides including bisindolyl rnaleic anhydrides.