2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione

• ChemBase编号: 913
• 分子式: C13H10N2O4
• 平均质量: 258.2295
• 单一同位素质量: 258.06405681
• SMILES: O=C1NC(=O)CCC1N1C(=O)c2c(C1=O)cccc2
• Canonical SMILES: O=C1CCC(C(=O)N1)N1C(=O)c2c(C1=O)cccc2
• InChI: InChI=1S/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)
• InChIKey: UEJJHQNACJXSKW-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
• IUPAC传统名: thalidomide
• 商标名: Algosediv; Asidon 3; Asmadion; Asmaval; Bonbrain; Bonbrrin; Calmore; Calmorex; Contergan; Corronarobetin; Distaval; Distaxal; Distoval; Ectiluran; Enterosediv; Gastrinide; Glupan; Glutanon; Grippex; Hippuzon; Imida-Lab; Imidan; Imidene; Isomin; Kedavon; Kevadon; Lulamin; Neaufatin; Neo; Neosedyn; Neosydyn; Nerosedyn; Neufatin; Neurodyn; Neurosedin; Neurosedym; Neurosedyn; Nevrodyn; Nibrol; Noctosediv; Noxodyn; Pangul; Pantosediv; Poly-Giron; Polygripan; Predni-Sediv; Pro-ban M; Profarmil; Psycholiquid; Psychotablets; Quetimid; Quietoplex; Sandormin; Sedalis; Sedalis sedi-lab; Sedimide; Sedin; Sedisperil; Sedoval; Shin-naito S; Shinnibrol; Sleepan; Slipro; Softenil; Softenon; Thalomid; Talargan; Talimol; Talismol; Telagan; Telargan; Telargean; Tensival; Thalin; Thalinette; Theophilcholine; Valgis; Valgraine; Yodomin
• 别名: 2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione; (±)-2-(2,6-Dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione; (±)-Thalidomide; Thalidomine USP26; thalidomide; Thalidomide; alpha-phthalimidoglutarimide; N-Phthalimidoglutamic acid imide; N-Phthaloylglutamimide; N-Phthalylglutamic acid imide; Thalomid; (±)-N-(2,6-Dioxo-3-piperidinyl)phthalimide; 2-(2,6-Dioxopiperidin-3-yl)isoindoline-1,3-dione; 2-(2,6-Dioxo-3-piperidinyl)-1H-iso-indole-1,3(2H)-dione; α-Phthalimidoglutarimide; 3-Phthalimidoglutarimide; Celgene; Contergan; Distaval; K 17; Kevadon; Myrin; N-(2,6-Dioxo-3-piperidyl)phthalimide; NSC 527179; NSC 66847

登记号

• CAS号: 50-35-1
• EC号: 200-031-1
• MDL号: MFCD00153873
• PubChem SID: 46505665; 24278765; 160964376
• PubChem CID: 5426
• CHEBI ID: 9513
• ATC码: L04AX02
• CHEMBL: 468
• Chemspider ID: 5233
• DrugBank ID: DB01041
• KEGG ID: D00754
• 美国药典/FDA物质标识码: 4Z8R6ORS6L
• 维基百科标题: Thalidomide
• Medline Plus: a699032

理论计算性质

JChem

• Acid pKa: 11.593279
• 质子受体: 4
• 质子供体: 1
• LogD (pH = 5.5): 0.01570701
• LogD (pH = 7.4): 0.015679834
• Log P: 0.015707357
• 摩尔折射率: 64.3248 cm^3
• 极化性: 24.014824 Å^3
• 极化表面积: 83.55 Å^2
• 可自由旋转的化学键: 1
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 0.42
• LOG S: -2.0
• 溶解度: 2.55e+00 g/l

分子性质

理化性质

• 溶解度: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: soluble0.6 mg/mL; 545 mg/L; Acetone; Butyl Acetate; DMSO; DMSO: >20 mg/mL; Ethanol; ethanol: insoluble; Ethyl Acetate; H2O: insoluble; Methanol; Sparingly Soluble In Water
• 外观: white solid; White Solid
• 熔点: 266-270°C; 269-271 °C
• 疏水性(logP): 0.3; 0.528

安全信息

• 保存条件: -20°C; -20°C Freezer; Room Temperature (15-30°C), Protect from light
• RTECS编号: TI4375000
• 欧盟危险性物质标志: 有毒(Toxic) (T)
• 联合国危险货物编号: 2811
• 德国WGK号: 3
• 联合国危险货物等级: 6.1
• 联合国危险货物包装类别(PG): 3; III
• 澳大利亚Hazchem: 2X
• 危险公开号: 46-61-21-25-62; R:25
• 安全公开号: 53-22-26-36/37/39-45; S:28-29-36/37/39-45
• 欧盟危险货物分类: T2
• 欧盟危险识别号(EUHIN): 6.1B
• 美国ERG指导号: 154
• GHS危险品标识: GHS06; GHS08
• GHS警示词: Danger
• GHS危险声明: H301-H312-H361
• GHS警示性声明: P280-P301 + P310
• 个人保护装置: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3

药理学性质

• 给药途径: oral
• 半衰期: mean ranges from approximately 5 to 7 hours following a single dose; not altered with multiple doses
• 代谢: Hepatic (CYP2C19)
• 蛋白结合率: 55% and 66% for the (+)-R and (–)-S enantiomers, respectively
• 法定药品分级: Rx-only
• 妊娠期药物分类: X (Australia); X (US)
• 相关基因信息: human ... LITAF(9516), TNF(7124)mouse ... Nos2(18126)rat ... Nos1(24598)

产品相关信息

• 纯度: ≥98%; 95%; 98%; 99%
• 成盐信息: Free Base

详细说明

MP Biomedicals - 02158753

Purity: 99% Inhibits HIV-I replication, FGF-induced angiogenesis, and α-TNF biosynthesis.

DrugBank - DB01041

• Drug Groups: approved; withdrawn; investigational
• Description: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor-alpha from monocytes, and modulates other cytokine action. [PubChem]
• Indication: For the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Also for use as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.
• Pharmacology: Thalidomide is an immunomodulatory agent with a spectrum of activity that is not fully characterized. Thalidomide is racemic — it contains both left and right handed isomers in equal amounts: one enantiomer is effective against morning sickness, and the other is teratogenic. The enantiomers are converted to each other in vivo. That is, if a human is given D-thalidomide or L-thalidomide, both isomers can be found in the serum. Hence, administering only one enantiomer will not prevent the teratogenic effect in humans.
• Toxicity: The R-configuration and the S-configuration are more toxic individually than the racemic mixture. The LD₅₀ could not be established in mice for racemic thalidomide, whereas LD₅₀ values for the R and S configurations are reported to be 0.4 to 0.7 g/kg and 0.5 to 1.5 g/kg, respectively.
• Affected Organisms: Humans and other mammals
• Biotransformation: Thalidomide itself does not appear to be hepatically metabolized to any large extent, but appears to undergo non-enzymatic hydrolysis in plasma to multiple metabolites. Thalidomide may be metabolized hepatically by enzymes of the cytochrome P450 enzyme system. The end product of metabolism, phthalic acid, is excreted as a glycine conjugate.
• Absorption: The absolute bioavailability has not yet been characterized in human subjects due to its poor aqueous solubility. In studies of both healthy volunteers and subjects with Hansen’s disease, the mean time to peak plasma concentrations (Tmax) ranged from 2.9 to 5.7 hours indicating that thalidomide is slowly absorbed from the gastrointestinal tract.
• Half Life: The mean half-life of elimination ranges from approximately 5 to 7 hours following a single dose and is not altered upon multiple dosing.
• Protein Binding: 55% and 66% for the (+)R and (−)S enantiomers, respectively.
• Elimination: Thalidomide itself has less than 0.7% of the dose excreted in the urine as unchanged drug.
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1193

Research Area: Immunology, Neurological Disease
Biological Activity:
Thalidomide was introduced as a sedative drug in the late 1950s. However, it was withdrawn due to a teratogenic effect on fetal development. Thalidomide binds to inactivate the protein cereblon, which is important to limb formation. [1]There is now a growing clinical interest in thalidomide since it is introduced as an immunomodulatory agent used primarily, combined with dexamethasone, to treat multiple myeloma. The combination of thalidomide and dexamethasone, often in combination with melphalan, is now one of the most common regimens for patients with newly diagnosed multiple myeloma, with an improved response rate of up to 60-70%. [1]

Sigma Aldrich - T144

Biochem/physiol Actions
(±)-Thalidomide selectively inhibits biosynthesis of tumor necrosis factor α (TNF-α); inhibitor of angiogenesis; immunosuppressive; sedative; teratogen.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. T144.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - T338850

Inhibits FGF-induced angiogenesis. Inhibits replication of human immunodeficiency virus type 1. Teratogenic sedative. There is now a growing clinical interest in Thalidomide, and it is introduced as an immunomodulatory agent used primarily in combinatio

参考文献

• Makonkawkeyoon, S., et al., J. Pharmacol. Exp. Therap., 160: 189, (1968).
• D' Amato, R.J., et al., Proc. Natl. Acad. Sci. USA, 91: 4082, (1994).
• Weglicki, W.B., et al., Mol. Cell. Biochem., 129: 195, (1993).
• http://en.wikipedia.org/wiki/Thalidomide
• D’Amato, r.J., et al.: Proc. Natl. Acad. Sci. USA, 91, 4082 (1994)
• Makonkawkeyoon, S., et al.: Proc. Natl. Acad. Sci. USA, 90, 5974 (1994)
• Schumacher, H., et al.: J. Pharmacol. Exp. Therap., 160, 189 (1968)