35457-98-8

Basic information

• Product Name: dimethyl (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanedioate
• CAS NO: 35457-98-8
• Molecular Formula: C₁₅H₁₅NO₆
• Molecular Weight: 305.2827
• Mol File: 35457-98-8.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 436.8°C at 760 mmHg
• Flash Point: 218°C
• Density: 1.34g/cm³
• Vapor Pressure: 7.84E-08mmHg at 25°C
• Refractive Index: 1.559
• CAS DataBase Reference: dimethyl (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanedioate(CAS DataBase Reference)
• NIST Chemistry Reference: dimethyl (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanedioate(35457-98-8)
• EPA Substance Registry System: dimethyl (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanedioate(35457-98-8)

Safety Data

• Hazardous Substances Data: 35457-98-8(Hazardous Substances Data)

Upstream product

• 67-56-1 methanol 
• 340-90-9 N-phthaloyl-L-glutamic acid 
• 85-44-9 phthalic anhydride 
• 22509-74-6 N-ethoxycarbonylphthalimide 
• 56-86-0 L-glutamic acid 

Downstream Products

• 105802-59-3 Dimethyl ester of N-(2-piperidinocarbonylbenzoyl)-L-glutamic acid 
• 105802-62-8 (S)-2-(2-Butylcarbamoyl-benzoylamino)-pentanedioic acid dimethyl ester 

Relevant articles and documents

A Genetically Encoded Allysine for the Synthesis of Proteins with Site-Specific Lysine Dimethylation

Using the amber suppression approach, N?-(4-azidobenzoxycarbonyl)-δ,?-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120.

Thiothalidomides: Novel Isosteric Analogues of Thalidomide with Enhanced TNF-α Inhibitory Activity

Thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. However, the mechanisms underlying its pharmacological action are still under investigation. In this regard, oral thalidomide is clinically valuable in the treatment of erythema nodosum leprosum (ENL) and mutiple myeloma and effectively reduces tumor necrosis factor-α (TNF-α) levels and angiogenesis in vivo. This contrasts with its relatively weak effects on TNF-α and angiogenesis in in vitro studies and implies that active metabolites contribute to its in vivo pharmacologic action and that specific analogues would be endowed with potent activity. Our focus in the structural modification of thalidomide is toward the discovery of novel isosteric active analogues. In this regard, a series of thiothalidomides and analogues were synthesized and evaluated for their TNF-α inhibitory activity against lipopolysacharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), This was combined with a PBMC viability assay to differentiate reductions in TNF-α secretion from cellular toxicity. Two isosteric analogues of thalidomide, compounds 15 and 16, that mostly reflect the parent compound, together with the simple structure, dithioglutarimide 19, potently inhibited TNF-α secretion, compared to thalidomide, 1. The mechanism underpinning this most likely is posttranscriptional, as each of these compounds decreased TNF-α mRNA stability via its 3′-UTR. The potency of 19 warrants further study and suggests that replacement of the amide carbonyl with a thiocarbonyl may be beneficial for increased TNF-α inhibitory action. In addition, an intact phthalimido moiety appeared to be requisite for TNF-α inhibitory activity.