841-67-8

Basic information

• Product Name: (-)-THALIDOMIDE
• Synonyms: 6-dioxo-3-piperidinyl)-3(2h)-dion(s)-1h-isoindole-2-(2;6-dioxo-3-piperidyl)-n-(l-(-)-phthalimid;(S)-2-(2,6-DIOXO-3-PIPERIDINYL)-1H-ISOINDOLE-1,3-(2H)-DIONE;S(-)-2-(2,6-DIOXO-3-PIPERIDINYL)-1H-ISOINDOLE-1,3(2H)-DIONE;(S)-(-)-THALIDOMIDE;(-)-THALIDOMIDE >98% INHIBITOR OF ANGIOG EN;(-)-N-[(S)-2,6-Dioxo-3-piperidinyl]phthalimide;(3S)-3-(1,3-Dioxo-2H-isoindole-2-yl)piperidine-2,6-dione
• CAS NO: 841-67-8
• Molecular Formula: C₁₃H₁₀N₂O₄
• Molecular Weight: 258.23
• EINECS: 200-031-1
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 841-67-8.mol
• Article Data: 4

Chemical Properties

• Melting Point: 269-271°C
• Boiling Point: 401.48°C (rough estimate)
• Flash Point: 262.1 °C
• Appearance: white/solid
• Density: 1.2944 (rough estimate)
• Vapor Pressure: 1.65E-10mmHg at 25°C
• Refractive Index: 1.5300 (estimate)
• Storage Temp.: -20°C Freezer
• Solubility: DMSO: soluble
• PKA: 10.70±0.40(Predicted)
• CAS DataBase Reference: (-)-THALIDOMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-THALIDOMIDE(841-67-8)
• EPA Substance Registry System: (-)-THALIDOMIDE(841-67-8)

Safety Data

• Hazard Codes: T
• Statements: 61-22
• Safety Statements: 53-36/37/39-45
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: TI4925050
• Hazardous Substances Data: 841-67-8(Hazardous Substances Data)

Usage

Definition

ChEBI: A 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione that has S-configuration at the chiral centre.

General Description

Thalidomide is a stereoisomer, which exists in two enantiomeric states. The S enantiomer is teratogenic. Thalidomide consists of two linked rings, a phthalimide and glutarimide ring.

Biochem/physiol Actions

(-)-Thalidomide selectively inhibits the biosynthesis of tumor necrosis factor α (TNF-α), which is essential for inflammatory response. It is an anti-emetic drug and is used to treat morning sickness in pregnant women. Thalidomide is also used to treat leprosy, multiple myeloma, Crohn′s disease and human immunodeficiency virus (HIV) infection. Thalidomide also inhibits angiogenesis. It is associated with several diseases such as, peripheral neuropathy, facial palsies, Duane syndrome and autism.

InChI:InChI=1/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17)/t9-/m0/s1

Upstream product

• 85-44-9 phthalic anhydride 
• 590365-46-1 aminoglutarimide trifluoroacetate 
• 56-85-9 L-glutamine 
• 2614-06-4 (R)-thalidomide 

Downstream Products

• 2614-08-6 (S)-4-phthalimidoglutaramic acid 
• 2614-06-4 (R)-thalidomide 
• 131-68-0 α-(o-carboxybenzamido)-L-glutarimide 
• 3343-29-1 (S)-2-phthalimidoglutaramic acid 
• 628337-09-7 2,3-dihydro-3-thioxo-2-(2-oxo-6-thioxo-3-piperidinyl)-1H-isoindol-1-one 

Relevant articles and documents

PROCESSES FOR THE PREPARATION OF THALIDOMIDE

The present invention provides a process for the preparation of thalidomide (I) comprising: i) reacting a compound of formula (II), where one of R represents -OH or -NH2 and the other of R represents -NH2 or -OH, respectively, with a phthaloylating agent in the presence of a base and a a non-polar organic solvent to obtain a phthaloyl derivative where R have the same meanings as above; and ii) dehydrating the phthaloyl derivative using a dehydrating agent selected from an acid anhydride, an acid halide, an ion exchange resin or a molecular sleve to obtain thalidomide (I).

Chiral inversion and hydrolysis of thalidomide: Mechanisms and catalysis by bases and serum albumin, and chiral stability of teratogenic metabolites

The chiral inversion and hydrolysis of thalidomide and the catalysis by bases and human serum albumin were investigated by using a stereoselective HPLC assay. Chiral inversion was catalyzed by albumin, hydroxyl ions, phosphate, and amino acids. Basic amino acids (Arg and Lys) had a superior potency in cataLyzing chiral inversion compared to acid and neutral ones. The chiral inversion of thalidomide is thus subject to Specific and general base catalysis, and it is suggested that the ability of HSA to catalyze the reaction is due to the basic groups of the amino acids Arg and Lys and not to a single catalytic site on the macromolecule. The hydrolysis of thalidomide was also base-catalyzed. However, albumin had no effect on hydrolysis, and there was no difference between the catalytic potencies of acidic, neutral, and basic amino acids. This may be explained by different reaction mechanisms of the chiral inversion and hydrolysis of thalidomide. Chiral inversion is deduced to occur by electrophilic substitution involving specific and general base catalysis, whereas hydrolysis is thought to occur by nucleophilic substitution involving specific and general base as well as nucleophilic catalysis. As nucleophilic attack is sensitive to steric properties of the catalyst, steric hindrance might be the reason albumin is not able to catalyze hydrolysis. 1H NMR experiments revealed that the three teratogenic metabolites of thalidomide, in sharp contrast to the drug itself, had complete chiral stability. This leads to the speculation that, were some enantioselectivity to exist in the teratogenicity of thalidomide, it could result from fast hydrolysis to chirally stable teratogenic metabolites.