(2S)-2-(carbamoylamino)pentanedioic acid

• ChemBase编号: 4475
• 分子式: C6H10N2O5
• 平均质量: 190.154
• 单一同位素质量: 190.05897143
• SMILES: C(=O)(O)[C@H](CCC(=O)O)NC(=O)N
• Canonical SMILES: OC(=O)CC[C@@H](C(=O)O)NC(=O)N
• InChI: InChI=1S/C6H10N2O5/c7-6(13)8-3(5(11)12)1-2-4(9)10/h3H,1-2H2,(H,9,10)(H,11,12)(H3,7,8,13)/t3-/m0/s1
• InChIKey: LCQLHJZYVOQKHU-VKHMYHEASA-N

名称和登记号

名称

• IUPAC标准名: (2S)-2-(carbamoylamino)pentanedioic acid
• IUPAC传统名: carglumic acid
• 商标名: Carbaglu
• 别名: (S)-2-ureidopentanedioic acid; N-Carbamyl-L-glutamate; Carglumic acid; Carbaglu; Carbamino-L-glutamic Acid; Carbamylglutamic Acid; Carglumic Acid; N-Carbamoyl-L-glutamic Acid; N-Carbamoyl-S-glutamic Acid; N-Carbamyl-L-glutamic Acid; OE 312; Ureidoglutaric Acid; N-(Aminocarbonyl)-L-glutamic Acid; N-Carbamyl-L-glutamic Acid; N-Carbamyl-L-glutamic acid

登记号

• CAS号: 1188-38-1
• MDL号: MFCD00047874
• PubChem SID: 24892688; 160967907; 99443290
• PubChem CID: 121396

理论计算性质

JChem

• Acid pKa: 3.3578658
• 质子受体: 5
• 质子供体: 4
• LogD (pH = 5.5): -4.880097
• LogD (pH = 7.4): -7.917335
• Log P: -1.446561
• 摩尔折射率: 39.4082 cm^3
• 极化性: 15.514146 Å^3
• 极化表面积: 129.72 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -1.06
• LOG S: -1.0
• 溶解度: 1.91e+01 g/l

分子性质

安全信息

• RTECS编号: LZ9870000
• 欧盟危险性物质标志: 刺激性(Irritant) (Xi)
• 德国WGK号: 3
• 危险公开号: 36/37/38
• 安全公开号: 26-36/37
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H302-H315-H319-H335
• GHS警示性声明: P261-P305 + P351 + P338
• 个人保护装置: dust mask type N95 (US), Eyeshields, Gloves
• 保存温度: 2-8°C

详细说明

DrugBank - DB06775

• Drug Groups: approved
• Description: Carglumic acid is an orphan drug used for the treatment of hyperammonaemia in patients with N-acetylglutamate synthase deficiency. This rare genetic disorder results in elevated blood levels of ammonia, which can eventually cross the blood–brain barrier and cause neurologic problems, cerebral edema, coma, and death. Carglumic acid was approved by the U.S. Food and Drug Administration (FDA) on 18 March 2010.
• Indication: For the treatment of hyperammonaemia in patients with N-acetylglutamate synthase (NAGS) deficiency.
• Pharmacology: The median Tmax of Carbaglu was 3 hours (range: 2-4). The initial daily dose ranges from 100 to 250 mg/kg, adjusted thereafter to maintain normal plasma levels of ammonia.
• Biotransformation: A proportion of carglumic acid may be metabolized by the intestinal bacterial flora. The likely end product of carglumic acid metabolism is carbon dioxide, eliminated through the lungs.
• Absorption: 30% bioavailability
• Half Life: Median values for the terminal half-life was 5.6 hours (range 4.3-9.5).
• Elimination: Following administration of a single radiolabeled oral dose of 100 mg/kg of body weight, 9% of the dose was excreted unchanged in the urine and up to 60% of the dose was excreted unchanged in the feces.
• Distribution: The apparent volume of distribution was 2657 L (range: 1616-5797).
• Clearance: The apparent total clearance was 5.7 L/min (range 3.0-9.7), the renal clearance was 290 mL/min (range 204-445), and the 24-hour urinary excretion was 4.5 % of the dose (range 3.5-7.5).
• References: Elpeleg O, Shaag A, Ben-Shalom E, Schmid T, Bachmann C: N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. Ann Neurol. 2002 Dec;52(6):845-9. [Pubmed] ; Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M: Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr. 2004 Oct;145(4):552-4. [Pubmed] ; Summary of the European Public Assessment Report (EPAR) from European Medicines Agency. Last updated on 21/09/2009. [Carbaglu] ; Thompson CA: Carglumic acid approved to treat genetic hyperammonemia. Am J Health Syst Pharm. 2010 May 1;67(9):690. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - C175965

N-Carbamyl-L-glutamic Acid has been shown to have protective effects against ammonia intoxication and is used in the treatment of acute hyperammonemia.

参考文献

• Elpeleg O, Shaag A, Ben-Shalom E, Schmid T, Bachmann C: N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. Ann Neurol. 2002 Dec;52(6):845-9. Pubmed
• Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M: Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr. 2004 Oct;145(4):552-4. Pubmed
• Summary of the European Public Assessment Report (EPAR) from European Medicines Agency. Last updated on 21/09/2009. Carbaglu
• Thompson CA: Carglumic acid approved to treat genetic hyperammonemia. Am J Health Syst Pharm. 2010 May 1;67(9):690. Pubmed
• Paik, W.K. et al.: Life Sci., 15, 1189 (1974)
• O'Connor, J.E. et al.: Eur. J. Pediat., 148, 540 (1974)
• Lee, J.H. et al.: Biochem. Biophys. Res. Chem., 248, 391 (1974)