2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole

• ChemBase编号: 4402
• 分子式: C11H12Cl2N2O
• 平均质量: 259.13178
• 单一同位素质量: 258.03266837
• SMILES: Clc1c(OC(C2=NCCN2)C)c(Cl)ccc1
• Canonical SMILES: CC(C1=NCCN1)Oc1c(Cl)cccc1Cl
• InChI: InChI=1S/C11H12Cl2N2O/c1-7(11-14-5-6-15-11)16-10-8(12)3-2-4-9(10)13/h2-4,7H,5-6H2,1H3,(H,14,15)
• InChIKey: KSMAGQUYOIHWFS-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole
• IUPAC传统名: lofexidine
• 商标名: BritLofex
• 别名: 2-(1-(2,6-dichlorophenoxy)ethyl)-2-imidazoline; Lofexidina [inn-spanish]; Lofexidinum [inn-latin]; 2-(alpha-(2,6-Dichlorophenoxy)ethyl)2-imidazoline; 2-(1-(2,6-Dichlorophenoxy)ethyl)-4,5-dihydro-1H-imidazole; Lofexidine hydrochloride; lofexidine; Lofexidine

登记号

• CAS号: 31036-80-3
• PubChem SID: 160967834; 46508453
• PubChem CID: 30668

理论计算性质

JChem

• 质子受体: 3
• 质子供体: 1
• LogD (pH = 5.5): 0.2664197
• LogD (pH = 7.4): 0.89805615
• Log P: 2.6630576
• 摩尔折射率: 64.413 cm^3
• 极化性: 25.174986 Å^3
• 极化表面积: 33.62 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 3.31
• LOG S: -3.25
• 溶解度: 1.47e-01 g/l

分子性质

产品相关信息

• 纯度: 98%

详细说明

DrugBank - DB04948

• Drug Groups: approved; investigational
• Description: Lofexidine is an alpha2-adrenergic receptor agonist. It can be used as a short acting anti-hypertensive, but is mostly used to help relieve symptoms of heroin or opiate withdrawal in opiate dependency. It is approved in the United Kingdom, but is still undergoing clinical trials in the United States.
• Indication: Investigated for use/treatment in addictions and substance abuse.
• Pharmacology: Lofexidine is an orally active imidazoline adrenergic alpha-2-receptor agonist; and is believed to have a high affinity for 2A receptor subtypes resulting in less anti-hypertensive activity than clonidine, a non-selective alpha-2-receptor agonist. Hypotension may occur in susceptible subjects, accompanied by a decrease in heart rate. Abrupt discontinuation of lofexidine has been, in some cases, associated with a transient increase in blood pressure to higher than pre-treatment levels. It selectively stimulates receptors in the brain that monitor catecholamine levels in the blood. These receptors close a negative feedback loop that begins with descending sympathetic nerves from the brain that control the production of catecholamines (epinephrine, also known as adrenaline, and norepinephrine) in the adrenal medulla. By fooling the brain into believing that catecholamine levels are higher than they really are, lofexidine causes the brain to reduce its signals to the adrenal medulla, which in turn lowers catecholamine production and blood levels. The result is a lowered heart rate and blood pressure. This central action is responsible for the suppression of opiate withdrawal symptoms.
• Toxicity: Lofexidine was tolerated at high dosage in singe dose toxicity studies in animals, the LD₅₀ being >77 mg/kg. With repeat dosing in mice, rats and dogs symptoms related to the pharmacology of the drug (ataxia, sedation, tremor, unkempt appearance and exhaustion) appeared. Overdosage may cause hypotension, bradycardia and sedation.
• Affected Organisms: Humans and other mammals
• Biotransformation: Lofexidine undergoes extensive metabolism in the liver and excretion is mainly by the kidney.
• Absorption: Lofexidine is extensively absorbed and achieves peak plasma concentration at ; 3 hours after administration of a single dose. Bioavailability is over 90% following oral administration.
• Half Life: 11 hours
• Protein Binding: 80 to 90%
• References: Walsh SL, Strain EC, Bigelow GE: Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans. Addiction. 2003 Apr;98(4):427-39. [Pubmed] ; Manufacturer Website [Link]
• External Links: Wikipedia

参考文献

• Walsh SL, Strain EC, Bigelow GE: Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans. Addiction. 2003 Apr;98(4):427-39. Pubmed
• Manufacturer Website Link