4-amino-3-(4-chlorophenyl)butanoic acid

• ChemBase编号: 66
• 分子式: C10H12ClNO2
• 平均质量: 213.66078
• 单一同位素质量: 213.05565631
• SMILES: Clc1ccc(C(CC(=O)O)CN)cc1
• Canonical SMILES: NCC(c1ccc(cc1)Cl)CC(=O)O
• InChI: InChI=1S/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14)
• InChIKey: KPYSYYIEGFHWSV-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 4-amino-3-(4-chlorophenyl)butanoic acid
• IUPAC传统名: baclofen
• 商标名: Baclon; Kemstro; Lioresal; Lioresal Intrathecal; Nu-Baclofen; Pms-Baclofen; Lioresal, Liofen
• 别名: β-(Aminomethyl)-4-chloro-benzenepropanoic Acid; β-(Aminomethyl)-p-chlorohydrocinnamic Acid; β-(4-Chlorophenyl)-GABA; Ba-34647; Baclon; Clofen; 4-Amino-3-(4-chlorophenyl)butanoic acid; Baclofen; (±)-β-(Aminomethyl)-4-chlorobenzenepropanoic acid; Lioresal; (±)-Baclofen; (±)-β-(Aminoethyl)-4-chlorobenzenepropanoic acid; (±)-BACLOFEN

登记号

• CAS号: 1134-47-0
• EC号: 214-486-9
• MDL号: MFCD00055143
• PubChem SID: 46508181; 24278146; 160963529
• PubChem CID: 2284
• CHEBI ID: 2972
• ATC码: M03BX01
• CHEMBL: 701
• Chemspider ID: 2197
• DrugBank ID: DB00181
• IUPHAR配体索引: 1084
• KEGG ID: D00241
• 美国药典/FDA物质标识码: H789N3FKE8
• 维基百科标题: Baclofen

理论计算性质

JChem

• Acid pKa: 3.8868947
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): -0.79014736
• LogD (pH = 7.4): -0.7832327
• Log P: -0.78240025
• 摩尔折射率: 54.8292 cm^3
• 极化性: 21.613943 Å^3
• 极化表面积: 63.32 Å^2
• 可自由旋转的化学键: 4
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -0.82
• LOG S: -2.48
• 溶解度: 7.12e-01 g/l

分子性质

理化性质

• 溶解度: 1 M HCl: soluble50 mg/mL; 2090 mg/L; Water
• 外观: Off-White Solid; white to very faintly yellow solid
• 熔点: 207°C; 208-210°C
• 疏水性(logP): -0.62; 1.3

安全信息

• 保存条件: -20°C Freezer; Room Temperature (15-30°C)
• 保存注意事项: IRRITANT
• RTECS编号: MW5084200
• 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: 61-25-36/37/38-42/43; R:25-36/37/38
• 安全公开号: 53-22-36/37/39-45; 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
• TSCA收录: false
• GHS危险品标识: GHS06; GHS08
• GHS警示词: Danger
• GHS危险声明: H301-H315-H317-H319-H334-H335-H360
• GHS警示性声明: P201-P261-P280-P301 + P310-P305 + P351 + P338-P308 + P313
• 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
• 保存温度: 2-8°C

药理学性质

• 给药途径: Oral, intrathecal
• 生物利用度: well absorbed
• 排泄: renal (70-80%)
• 半衰期: 1.5 to 4 hours
• 代谢: 85% excreted in urine/faeces unchanged. 15% metabolised by deamination
• 蛋白结合率: 30%
• 法定药品分级: Rx-only (US)
• 妊娠期药物分类: C (US)
• 美国（FDA）药品许可证: Baclofen
• 相关基因信息: human ... GABBR1(2550), GABBR2(9568)rat ... Gabbr1(81657), Gabra2(29706)

产品相关信息

• 纯度: ≥98% (TLC); 95%

详细说明

MP Biomedicals - 02153629

White solid; mp 192-193°C.
Store tightly sealed.
Soluble in water, dilute acid and base.

DrugBank - DB00181

• Drug Groups: approved
• Description: Baclofen is a gamma-amino-butyric acid (GABA) derivative used as a skeletal muscle relaxant. Baclofen stimulates GABA-B receptors leading to decreased frequency and amplitude of muscle spasms. It is especially useful in treating muscle spasticity associated with spinal cord injury. It appears to act primarily at the spinal cord level by inhibiting spinal polysynaptic afferent pathways and, to a lesser extent, monosynaptic afferent pathways.
• Indication: For the alleviation of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity.
• Pharmacology: Baclofen is a muscle relaxant and antispastic. Baclofen is useful for the alleviation of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. Although Baclofen is an analog of the putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA), there is no conclusive evidence that actions on GABA systems are involved in the production of its clinical effects. In studies with animals, Baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression. Baclofen is rapidly and extensively absorbed and eliminated. Absorption may be dose-dependent, being reduced with increasing doses. Baclofen is excreted primarily by the kidney in unchanged form and there is relatively large intersubject variation in absorption and/or elimination.
• Toxicity: LD₅₀=45 mg/kg (male mice, IV); LD₅₀=78 mg/kg (male rat, IV)
• Affected Organisms: Humans and other mammals
• Biotransformation: ~ 15% of the dose is metabolized in the liver, primarily by deamination. 70-80% of the dose is excreted unchanged or as metabolites in urine and the remainder is excreted in feces.
• Absorption: Rapidly and almost completely absorbed from the GI tract.
• Half Life: 2.5-4 hours
• Protein Binding: 30%
• Elimination: In a study using radiolabeled baclofen, approximately 85% of the dose was excreted unchanged in the urine and feces. ; Baclofen is excreted primarily by the kidney as unchanged drug; 70 - 80% of a dose appears in the urine as unchanged drug. The remainder is excreted as unchanged drug in the feces or as metabolites in the urine and feces.
• Distribution: * 59 L
• Clearance: * 180 mL/min
• References: Dzitoyeva S, Dimitrijevic N, Manev H: Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5485-90. Epub 2003 Apr 11. [Pubmed] ; Mezler M, Muller T, Raming K: Cloning and functional expression of GABA(B) receptors from Drosophila. Eur J Neurosci. 2001 Feb;13(3):477-86. [Pubmed] ; See S, Ginzburg R: Skeletal muscle relaxants. Pharmacotherapy. 2008 Feb;28(2):207-13. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - B5399

Biochem/physiol Actions
GABAB receptor agonist; skeletal muscle relaxant; antispastic agent.

Toronto Research Chemicals - B108000

Specific GABA-B receptor agonist. Muscle relaxant (skeletal).

参考文献

• Dzitoyeva S, Dimitrijevic N, Manev H: Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5485-90. Epub 2003 Apr 11. Pubmed
• Mezler M, Muller T, Raming K: Cloning and functional expression of GABA(B) receptors from Drosophila. Eur J Neurosci. 2001 Feb;13(3):477-86. Pubmed
• See S, Ginzburg R: Skeletal muscle relaxants. Pharmacotherapy. 2008 Feb;28(2):207-13. Pubmed
• Ahuja, S., et al.: Anal. Profiles Drug Subs., 14, 527 (1985)
• Brogden, R.N., et al.: Drugs, 8,1 (1974)