26581-81-7

Usage

Uses

Used in Pharmaceutical Industry:
Phthalimidine, 2-(2,6-dioxopiperiden-3-yl) is used as a research compound for the development of Protein Degradation Targeting Chimeras (PROTACs). These are a new class of therapeutics that can selectively degrade disease-causing proteins, offering a novel approach to treating various diseases. The compound's structure allows it to be a useful tool in the design and synthesis of new PROTACs, potentially leading to the development of more effective treatments for a range of conditions.
Used in Chemical Research:
In addition to its pharmaceutical applications, Phthalimidine, 2-(2,6-dioxopiperiden-3-yl) can also be used as a starting material or intermediate in the synthesis of other complex organic compounds. Its unique structure makes it a valuable building block for researchers working on the development of new molecules with specific properties and functions.
Used in Drug Design and Development:
Phthalimidine, 2-(2,6-dioxopiperiden-3-yl) can be utilized in the design and development of new drugs, particularly those targeting protein-protein interactions. Its lenalidomide analog structure may provide insights into the design of more potent and selective inhibitors, which could be beneficial in the treatment of various diseases, including cancer and inflammatory disorders.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Phthalimidine, 2-(2,6-dioxopiperiden-3-yl). is an example of an amide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition Phthalimidine, 2-(2,6-dioxopiperiden-3-yl). emits toxic fumes of nitrogen oxides.

Fire Hazard

Flash point data for Phthalimidine, 2-(2,6-dioxopiperiden-3-yl). are not available; however, Phthalimidine, 2-(2,6-dioxopiperiden-3-yl). is probably combustible.

InChI:InChI=1/C13H12N2O3/c16-11-6-5-10(12(17)14-11)15-7-8-3-1-2-4-9(8)13(15)18/h1-4,10H,5-7H2,(H,14,16,17)

Upstream product

• 26581-82-8 2-(1-oxo-1,3-dihydro-isoindol-2-yl)-pentanedioic acid anhydride 
• 222713-10-2 1-(4-methoxybenzyl)-3-(1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione 
• 58585-25-4 3-(1-hydroxy-3-oxoisoindolin-2-yl)piperidine-2,6-dione 
• 50-35-1 thalidomide 
• 222713-08-8 3-(1-hydroxy-3-oxo-1,3-dihydro-isoindol-2-yl)-1-(4-methoxy-benzyl)-piperidine-2,6-dione 
• 222713-07-7 2-[1-(4-methoxybenzyl)-2,6-dioxopiperidin-3-yl]isoindoline-1,3-dione 
• 222713-09-9 1-(4-methoxy-benzyl)-3-(1-oxo-3-phenylsulfanyl-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione 
• 6349-98-0 N-phthalylglutamic acid 
• 3343-28-0 N-phthaloylglutamic acid anhydride 
• 600721-44-6 1-benzyloxy-3-(1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione 
• 600721-43-5 2-(1-benzyloxy-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione 
• 912893-81-3 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-4-(4-methoxy-benzylcarbamoyl)-butyric acid 
• 643-79-8 o-phthalic dicarboxaldehyde 
• 590365-46-1 (RS)-2,6-dioxopiperidin-3-yl-ammonium trifluoroacetate 

Relevant academic research and scientific papers

COMPOUNDS MODULATING PROTEIN RECRUITMENT AND/OR DEGRADATION

The invention provides cereblon binders for the degradation of proteins by the ubiquitin proteasome pathway for therapeutic applications.

Chemoselective Electrosynthesis Using Rapid Alternating Polarity

Challenges in the selective manipulation of functional groups (chemoselectivity) in organic synthesis have historically been overcome either by using reagents/catalysts that tunably interact with a substrate or through modification to shield undesired sites of reactivity (protecting groups). Although electrochemistry offers precise redox control to achieve unique chemoselectivity, this approach often becomes challenging in the presence of multiple redox-active functionalities. Historically, electrosynthesis has been performed almost solely by using direct current (DC). In contrast, applying alternating current (AC) has been known to change reaction outcomes considerably on an analytical scale but has rarely been strategically exploited for use in complex preparative organic synthesis. Here we show how a square waveform employed to deliver electric current - rapid alternating polarity (rAP) - enables control over reaction outcomes in the chemoselective reduction of carbonyl compounds, one of the most widely used reaction manifolds. The reactivity observed cannot be recapitulated using DC electrolysis or chemical reagents. The synthetic value brought by this new method for controlling chemoselectivity is vividly demonstrated in the context of classical reactivity problems such as chiral auxiliary removal and cutting-edge medicinal chemistry topics such as the synthesis of PROTACs.

THALIDOMIDE ANALOGS AND METHODS OF USE

Thalidomide analogs and methods of using the thalidomide analogs are disclosed. Some embodiments of the disclosed compounds exhibit anti- angiogenic and/or anti-inflammatory activity. Certain embodiments of the disclosed compounds are non-teratogenic.

Thalidomide metabolites and analogues. 3. Synthesis and antiangiogenic activity of the teratogenic and TNFα-modulatory thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine

Versatile synthesis of the teratogenic, TNFα-modulatory, and antiangiogenic thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine (1) and its direct antiangiogenic properties are described. With thalidomide or thalidomide derivatives as precursors, the synthesis involved either carbonyl reduction/thiation-desulfurization or carbonyl reduction/acyliminium ion reduction protocols. Compared to earlier studies with thalidomide, which was only active with microsomal treatment, 1 exhibited marginal inhibitory activity in the rat aortic ring assay, thereby demonstrating the requirement for metabolic activation.

A facile scheme for phthalimide ? phthalimidine conversion

Desulfurization of phenylthiolactams using an ultrasound-promoted Raney nickel protocol yields the corresponding N-substituted phthalimidines. Benzylic oxidation of the N-substituted phthalimidines by treatment with 2,2'-bipyridinium chlorochromate/m-chloroperbenzoic acid (BPCC/MCPBA) affords the original phthalimides. The reduction-desulfurization is applied to the preparation of a deoxythalidomide derivative which is a TNF-α inhibitor.

Comparative teratological investigation of compounds structurally and pharmacologically related to thalidomide

Compounds differing from thalidomide in either the phthalimide or the 2,6-dioxopiperidine moiety of the molecule were synthetized and tested for teratogenic potency in White New Zealand rabbits. Both the 2,6-dioxopiperidine and 2-oxopiperidine derivatives of phthalimide and phthalimidine were found to be highly teratogenic. A somewhat higher teratogenic potential appeared to be associated with the 2,6-dioxopiperidine derivatives. The most potent teratogen investigated was clearly 3-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)-2,6-dioxopiperidine (EM 12). Compounds in which the phthalimide ring was replaced by 2,3-dihydro-1,1-dioxido-3-oxo-1,2-benzisothiazol, did not induce any embryopathic effect differing from control data. No consistent correlation between teratogenic activity and sedative properties of the compounds was detected. The results are discussed in respect to current views of the molecular mechanism leading to thalidomide embryopathy.