441741-65-7

Usage

Uses

Used in Pharmaceutical Applications:
2-Propenoic acid, 3-[4-[[[2-(2-Methyl-1H-indol-3-yl)ethyl]aMino]Methyl]phenyl]-, Methyl ester, (2E)is used as a pharmaceutical candidate for its potential biological activities. Its unique structure may contribute to its therapeutic effects, and further research is needed to explore its specific uses and potential effects on human health.
Used in Chemical Synthesis:
2-Propenoic acid, 3-[4-[[[2-(2-Methyl-1H-indol-3-yl)ethyl]aMino]Methyl]phenyl]-, Methyl ester, (2E)is used as a chemical intermediate in the synthesis of other compounds. Its versatile structure allows for further functionalization and modification, making it a valuable building block in the development of new chemical entities.
Used in Research and Development:
2-Propenoic acid, 3-[4-[[[2-(2-Methyl-1H-indol-3-yl)ethyl]aMino]Methyl]phenyl]-, Methyl ester, (2E)is used in research and development for its potential applications in various fields. Scientists and researchers utilize 2-Propenoic acid, 3-[4-[[[2-(2-Methyl-1H-indol-3-yl)ethyl]aMino]Methyl]phenyl]-, Methyl ester, (2E)- to study its properties, reactivity, and potential interactions with other molecules, which can lead to the discovery of new applications and insights into its behavior.

Upstream product

• 2731-06-8 2-methyltryptamine 
• 7560-50-1 methyl (2E)-3-(4-formylphenyl)acrylate 
• 1122-91-4 4-bromo-benzaldehyde 
• 58045-41-3 methyl 3‐(4‐formylphenyl)acrylate 
• 1067-74-9 Methyl diethylphosphonoacetate 
• 73291-09-5 4-chloromethylbenzaldehyde 
• 5891-21-4 5-chloro-2-pentanone 
• 100-63-0 phenylhydrazine 
• 731846-75-6 methyl (E)-3-(4-(chloromethyl)phenyl)acrylate 

Downstream Products

• 404950-80-7 panobinostat 
• 960058-93-9 (E)-3-(4-(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylic acid 
• 441741-66-8 (E)-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]acrylic acid methyl ester hydrochloride 

Relevant academic research and scientific papers

Development and pre-clinical testing of a novel hypoxia-activated KDAC inhibitor

Tumor hypoxia is associated with therapy resistance and poor patient prognosis. Hypoxia-activated prodrugs, designed to selectively target hypoxic cells while sparing normal tissue, represent a promising treatment strategy. We report the pre-clinical efficacy of 1-methyl-2-nitroimidazole panobinostat (NI-Pano, CH-03), a novel bioreductive version of the clinically used lysine deacetylase inhibitor, panobinostat. NI-Pano was stable in normoxic (21% O2) conditions and underwent NADPH-CYP-mediated enzymatic bioreduction to release panobinostat in hypoxia (2). Treatment of cells grown in both 2D and 3D with NI-Pano increased acetylation of histone H3 at lysine 9, induced apoptosis, and decreased clonogenic survival. Importantly, NI-Pano exhibited growth delay effects as a single agent in tumor xenografts. Pharmacokinetic analysis confirmed the presence of sub-micromolar concentrations of panobinostat in hypoxic mouse xenografts, but not in circulating plasma or kidneys. Together, our pre-clinical results provide a strong mechanistic rationale for the clinical development of NI-Pano for selective targeting of hypoxic tumors.

A minimally-masked inactive prodrug of panobinostat that is bioorthogonally activated by gold chemistry

The recent incorporation of Au chemistry in the bioorthogonal toolbox has opened up new opportunities to deliver biologically independent reactions in living environments. Herein we report that the O-propargylation of the hydroxamate group of the potent HDAC inhibitor panobinostat leads to a vast reduction of its anticancer properties (>500-fold). We also show that this novel prodrug is converted back into panobinostat in the presence of Au catalysts in vitro and in cell culture.

A handkerchief compared to department he and its key intermediate for the preparation of (by machine translation)

The invention belongs to the field of drug synthesis, in particular to a handkerchief compared to department he and its key intermediate of the preparation method, the method to cheap 4 - halogenated methyl formaldehyde, 2 - a primary amine and phosphine acyl acetic acid methyl ester compound as raw material, in the same pot obtain key intermediate (E)- 3 - [4 - [[2 - (2 - methyl - 1 H - indole - 3 - 3 yl) ethylamine] methyl] phenyl] acrylic acid methyl ester, obtained by the reaction with hydroxylamine handkerchief compared to department he, the method not only raw materials are cheap and easily obtained, and the cost is low, and there are few reaction steps, high yield and purity, mild reaction conditions at the same time, the operation is simple, is easy for industrial production. (by machine translation)

An improved and efficient synthesis of panobinostat

An improved and efficient method for the synthesis of panobinostat was developed. The commercially available starting material 4-(chloromethyl)benzaldehyde was converted to (E)-methyl 3-[4-(chloromethyl)phenyl]acrylate via the Wittig-Horner reaction and was then directly condensed with 2-(2-methyl-1H-indol-3-yl)ethanamine to afford the key intermediate (E)-methyl 3-[4-({[2-(2-methyl-1H-indol- 3-yl)ethyl]amino}methyl)phenyl]acrylate in a one-pot synthesis reactor. Subsequently a nucleophilic substitution reaction was carried out smoothly to generate the desired compound. The key intermediate and target compound were characterised by HRMS, 1H NMR and 13C NMR. This procedure is operationally simple and would be more suitable for industrial production.

Synthesis method of panobinostat key intermediate

The invention belongs to the field of medicine synthesis, and particularly relates to a synthesis method of a panobinostat key intermediate. The key intermediate is (E)-3-[4-[[[2-(2-methyl-1H-indole-3-yl)ethyl] amino] methyl] phenyl] methyl acrylate hydrochloride. The method has the advantages that the yield is as high as 85 percent or higher; the impurities are few; the purity is 99.5 percent orhigher; meanwhile, the operation is simple and convenient.

Panobinostat intermediate as well as synthesis and application thereof

The invention belongs to the field of medicine synthesis and in particular relates to a panobinostat intermediate as well as synthesis and application thereof. The intermediate is shown as a formula II and is obtained by taking 2-methyltryptamine and 4-chloromethylbenzaldehyde to react; raw materials are cheap and easy to obtain, reaction conditions are moderate and the operation is simple; the intermediate is used as a raw material to prepare panobinostat, the cost is low, reaction steps are few, the purity is high, the reaction conditions are moderate and the operation is simple; the qualitycontrol and cost reduction of panobinostat crude drugs are facilitated. (The formula II is shown in the description.).

METHOD OF USE OF DEACETYLASE INHIBITORS

The present invention provides methods of treating and/or preventing pathologic cardiac hypertrophy and heart failure comprising administering hydroxamate compounds which are deacetylase inhibitors.