19171-18-7

Basic information

• Product Name: 2-(2,6-dioxopiperidin-3-yl)-4-nitroisoindoline-1,3-dione
• Synonyms: 2-(2,6-dioxopiperidin-3-yl)-4-nitroisoindoline-1,3-dione;4-Nitrothalidomide;4-nitro-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;Pomalidomide Impurity 11;Pomalidomide Intermediates;Pomalidomide Impurity E
• CAS NO: 19171-18-7
• Molecular Formula: C₁₃H₉N₃O₆
• Molecular Weight: 303.22706
• EINECS: 200-258-5
• Mol File: 19171-18-7.mol
• Article Data: 33

Chemical Properties

• Boiling Point: 603.4°Cat760mmHg
• Flash Point: 318.7°C
• Appearance: /
• Density: 1.651g/cm³
• Vapor Pressure: 1.63E-14mmHg at 25°C
• Refractive Index: 1.674
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Acetonitrile (Slightly, Heated, Sonicated), DMSO (Slightly)
• PKA: 10.55±0.40(Predicted)
• CAS DataBase Reference: 2-(2,6-dioxopiperidin-3-yl)-4-nitroisoindoline-1,3-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(2,6-dioxopiperidin-3-yl)-4-nitroisoindoline-1,3-dione(19171-18-7)
• EPA Substance Registry System: 2-(2,6-dioxopiperidin-3-yl)-4-nitroisoindoline-1,3-dione(19171-18-7)

Safety Data

• Hazardous Substances Data: 19171-18-7(Hazardous Substances Data)

Usage

Uses

4-Nitrothalidomide is a compound involved in the preparation of Pomalidomide (P688200), a thalidomide derivative and potent inhibitor of TNF-α production.

InChI:InChI=1/C13H9N3O6/c17-9-5-4-8(11(18)14-9)15-12(19)6-2-1-3-7(16(21)22)10(6)13(15)20/h1-3,8H,4-5H2,(H,14,17,18)

Upstream product

• 641-70-3 3-nitrophthalic acid anhydride 
• 56-85-9 L-glutamine 
• 151367-92-9 L-tert-butyl N-[2,6-dioxohexahydro-3-pyridinyl] Carbamate 
• 13726-85-7 Boc-Gln-OH 
• 603-62-3 4-nitro-1H-isoindole-1,3(2H)-dione 
• 590365-46-1 aminoglutarimide trifluoroacetate 
• 496-12-8 isoindoline 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 31140-42-8 (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester 
• 6383-80-8 2-(3'-Nitro-phthalimido)-glutarsaeureanhydrid 
• 18636-08-3 1-(4-nitro-1,3-dioxoisoindolin-2-yl)propane-1,3-dicarboxylic acid 
• 617-65-2 Glutamic acid 
• 85535-45-1 5-amino-2-(tert-butoxycarbonylamino)-5-oxo-pentanoic acid 
• 118061-00-0 (3S)-3-aminopiperidine-2,6-dione hydrobromide 

Downstream Products

• 19171-19-8 pomalidomide 
• 847871-99-2 3-(4-amino-1-oxo-1,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione hemihydrate 
• 444287-84-7 2‐chloro‐N‐(2‐(2,6‐dioxopiperidin‐3‐yl)‐1,3‐dioxoisoindolin‐4‐yl)acetamide 
• 879126-98-4 Lenalidomide 
• 202271-89-4 (R)-(+)-4-amino-2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3-dione 
• 202271-89-4 (S)-(-)-4-amino-2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3-dione 

Relevant articles and documents

Chemically induced degradation of CK2 by proteolysis targeting chimeras based on a ubiquitin–proteasome pathway

As a ubiquitous, highly pleiotropic and constitutively active serine/threonine protein kinase, casein kinase 2 (CK2) is closely associated with tumorigenesis by its overexpression in cancer cells. Here we report several proteolysis targeting chimeras (PROTACs) via “click reaction” to connect a CK2 inhibitor (CX-4945) and pomalidomide for degradation of CK2 protein. Among them, compound 2 degraded CK2 in a dose and time-dependent manner, and kept CK2 at a low basal level by recruiting ubiquitin-proteasome system. The degradation of CK2 resulted in the reduced phosphorylation of Akt and the up-regulation of p53. As a CK2 protein degrader, 2 showed the analogous cytotoxicity to CX-4945 but with a quite different mechanism of action from the CK2 inhibitor, hinting that degradation of CK2 proteins by PROTACs is a potential way for cancer treatments.

New synthesis route for the preparation of pomalidomide

A new route for the preparation of pomalidomide is described in the study. The synthetic procedure starts from 4-nitroisobenzofuran-1,3-dione and 3-aminopiperidine-2,6-dione hydrochloride via a three-step reaction resulting in a total yield of 65% with a high-performance liquid chromatographic (HPLC) purity of 99.56% and a low palladium residue level of 2?ppm. This method can be deemed as an efficient, practical, and environmentally friendly synthetic route for the preparation of pomalidomide.

Rational Design and Synthesis of HSF1-PROTACs for Anticancer Drug Development

PROTACs employ the proteosome-mediated proteolysis via E3 ligase and recruit the natural protein degradation machinery to selectively degrade the cancerous proteins. Herein, we have designed and synthesized heterobifunctional small molecules that consist of different linkers tethering KRIBB11, a HSF1 inhibitor, with pomalidomide, a commonly used E3 ligase ligand for anticancer drug development.

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.

DIMERIC IMMUNO-MODULATORY COMPOUNDS AGAINST CEREBLON-BASED MECHANISMS

Disclosed are small molecules against cereblon to enhance effector T cell function. Methods of making these molecules and methods of using them to treat various disease states are also disclosed.