55003-81-1

Basic information

• Product Name: 1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitro-
• Synonyms: 2-(2,6-dioxo-piperidin-3-yl)-5-nitro-isoindole-1,3-dione;N-(2,6-dioxopiperidin-3-yl)-4-nitrophthalimide;1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-5-nitroisoindoline;2-(2,6-dioxo-3-piperidinyl)-5-nitro-1H-isoindole-1,3(2H)-dione;4-nitrothalidomide;1H-Isoindole-1,3(2H)-dione,2-(2,6-dioxo-3-piperidinyl)-5-nitro;2-(4'-Nitro-phthalimido)-glutarimid
• CAS NO: 55003-81-1
• Molecular Formula: C13H9N3O6
• Molecular Weight: 303.22700
• Mol File: 55003-81-1.mol

Chemical Properties

• CAS DataBase Reference: 1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitro-(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitro-(55003-81-1)
• EPA Substance Registry System: 1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitro-(55003-81-1)

Safety Data

• Hazardous Substances Data: 55003-81-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitrois used as a key intermediate in the synthesis of various pharmaceuticals for its potential anti-inflammatory and anticancer properties. 1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitro-'s unique structure allows it to interact with biological targets, offering a new avenue for the development of therapeutic agents.
Used in Dye Industry:
In the dye industry, 1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitrois utilized for its ability to form colored compounds, making it a valuable component in the creation of dyes with specific color characteristics.
Used in Research and Development:
As a nitro compound, 1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitrois used in research for its potential as a nitric oxide donor, which has implications in various physiological processes and therapeutic applications. Additionally, it serves as a precursor to other nitrogen-containing compounds, expanding its utility in the synthesis of novel chemical entities.
Used in Chemical Synthesis:
1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-nitrois employed as a building block in the synthesis of complex organic molecules, leveraging its reactive functional groups to form a variety of derivatives with diverse applications in different fields.

Upstream product

• 24666-55-5 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine 
• 13726-85-7 Boc-Gln-OH 
• 89-40-7 4-nitrophthalimide 
• 590365-46-1 aminoglutarimide trifluoroacetate 
• 5466-84-2 4-nitrophthalic anhydride 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 31140-42-8 (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester 
• 85535-45-1 5-amino-2-(tert-butoxycarbonylamino)-5-oxo-pentanoic acid 
• 2353-44-8 (+/-)-α-aminoglutarimide 
• 2650-64-8 Cbz-L-Gln 
• 590365-46-1 (RS)-2,6-dioxopiperidin-3-yl-ammonium trifluoroacetate 

Downstream Products

• 191732-76-0 2-(2,6-dioxo-3-piperidinyl)-5-amino-1H-isoindole-1,3(2H)-dione 

Relevant articles and documents

Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands

Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties.

De-novo design of cereblon (CRBN) effectors guided by natural hydrolysis products of thalidomide derivatives

Targeted protein degradation via cereblon (CRBN), a substrate receptor of an E3 ubiquitin ligase complex, is an increasingly important strategy in various clinical settings, in which the substrate specificity of CRBN is altered via the binding of small-molecule effectors. To date, such effectors are derived from thalidomide and confer a broad substrate spectrum that is far from being fully characterized. Here, we employed a rational and modular approach to design novel and minimalistic CRBN effectors. In this approach, we took advantage of the binding modes of hydrolyzed metabolites of several thalidomide-derived effectors, which we elucidated via crystallography. These yielded key insights for the optimization of the minimal core binding moiety and its linkage to a chemical moiety that imparts substrate specificity. Based on this scaffold, we present a first active de-novo CRBN effector that is able to degrade the neo-substrate IKZF3 in the cell culture.

IMIDE-BASED MODULATORS OF PROTEOLYSIS AND METHODS OF USE

The description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure–Degradation Relationships

The immunomodulatory drugs (IMiDs) thalidomide, pomalidomide, and lenalidomide have been approved for the treatment of multiple myeloma for many years. Recently, their use as E3 ligase recruiting elements for small-molecule-induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one-pot synthesis without purification that provides rapid access to a multitude of IMiD analogues. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure–activity relationship with only a few compounds showing sub-micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti-proliferative activity as well as Aiolos degradation could be identified for two IMiD analogues. This study provides useful insight into the structure–degradation relationships for molecules of this type as well as a rapid and robust method for IMiD synthesis.

REGULATING CHIMERIC ANTIGEN RECEPTORS

This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

TUNABLE ENDOGENOUS PROTEIN DEGRADATION WITH HETEROBIFUNCTIONAL COMPOUNDS

The present invention provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.

Preliminary biological evaluations of new thalidomide analogues for multiple sclerosis application

The present work deals with the synthesis of a new series of thalidomide derivatives for therapeutic applications. These compounds were evaluated in vitro on a human endothelial cell line EA.hy926 for their antiproliferative potential and in vivo on an experimental animal multiple sclerosis model called EAE as angiogenesis inhibitors. The preliminary results obtained on EAE assays seem to validate that anti-angiogenesis compounds could be promising tools for the treatment of MS.

Syntheses of aromatic substituted 6′-thiothalidomides

A resurgence of interest in thalidomide has occurred as a consequence of its diverse immunomodulatory and anticancer actions, which has fuelled interest in synthetic analogues with higher potencies or less undesirable side effect profiles. Several novel aromatic substituted 6′-thiothalidomides were synthesized whose synthetic route and strategy were developed on the basis of an analysis of reaction mechanisms. The regioselectivity of mono-thionation of aromatic substituted thalidomides with Lawesson's reagent is described, and the chemoselectivity of hydrogenation between the nitro group and 6′-thiocarbonyl group is discussed. Full characterization of eight substituted 6′-thiothalidomides is reported. Georg Thieme Verlag Stuttgart.

Facile synthesis of an azido-labeled thalidomide analogue

(Matrix presented) A five-step synthesis of an azido-thalidomide analogue is presented. The sequence requires cheap and readily available starting materials and reagents, and only two steps require purification. Additionally, the azido-labeled analogue possesses activity comparable to that of thalidomide in inhibiting the proliferation of human microvascular endothelial cells, thus providing impetus for its use as a potential photoaffinity label of thalidomide.

Substituted 2(2,6-dioxopiperidin-3-yl)isoindolines

Substituted 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolines and 1-oxo-2-(2,6-dioxo-piperidin-3-yl)isoindolines reduce the levels of TNFα in a mammal and are useful in treating oncogenic conditions, inflammation, and autoimmune diseases. Typical embodiments are 1-oxo-2-(2,6-dioxo-3-methylpiperidin-3-yl)-4,5,6,7-tetrafluoroiso-indoline and 1,3-dioxo-2-(2,6-dioxo-3-methylpiperidin-3-yl)-4-aminoisoindoline.