1-hydrazinylphthalazine

• ChemBase编号: 1138
• 分子式: C8H8N4
• 平均质量: 160.17592
• 单一同位素质量: 160.07489628
• SMILES: N(N)c1nncc2c1cccc2
• Canonical SMILES: NNc1nncc2c1cccc2
• InChI: InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
• InChIKey: RPTUSVTUFVMDQK-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 1-hydrazinylphthalazine
• IUPAC传统名: hydralazine
• 商标名: Apresoline
• 别名: Hydralazine hydrochloride; Hydralazine

登记号

• CAS号: 86-54-4
• PubChem SID: 160964601; 46507533
• PubChem CID: 3637
• CHEBI ID: 5775
• ATC码: C02DB02
• CHEMBL: 276832
• Chemspider ID: 3511
• DrugBank ID: DB01275
• KEGG ID: D08044
• 美国药典/FDA物质标识码: 26NAK24LS8
• 维基百科标题: Hydralazine
• Medline Plus: a682246

理论计算性质

JChem

• Acid pKa: 17.691772
• 质子受体: 4
• 质子供体: 2
• LogD (pH = 5.5): -0.19961534
• LogD (pH = 7.4): 0.7096126
• Log P: 0.7513803
• 摩尔折射率: 50.2348 cm^3
• 极化性: 18.632671 Å^3
• 极化表面积: 63.83 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: 0.66
• LOG S: -1.79
• 溶解度: 2.61e+00 g/l

分子性质

理化性质

• 疏水性(logP): 0.7

药理学性质

• 给药途径: Oral, intravenous
• 生物利用度: 26-55%
• 排泄: Renal
• 半衰期: 2-4 hours
• 代谢: Hepatic
• 妊娠期药物分类: C; Commonly used to treat severe PIH

详细说明

DrugBank - DB01275

• Drug Groups: approved
• Description: A direct-acting vasodilator that is used as an antihypertensive agent. [PubChem]
• Indication: For the treatment of essential hypertension, alone or as an adjunct. Also for the management of severe hypertension when the drug cannot be given orally or when blood pressure must be lowered immediately, congestive heart failure (in combination with cardiac glycosides and diuretics and/or with isosorbide dinitrate), and hypertension secondary to pre-eclampsia/eclampsia.
• Pharmacology: A vasodilator, hydralazine works by relaxing blood vessels (arterioles more than venules) and increasing the supply of blood and oxygen to the heart while reducing its workload. It also functions as an antioxidant. It inhibits membrane-bound enzymes that form reactive oxygen species, such as superoxides. Excessive superoxide counteracts NO-induced vasodilation. It is commonly used in the condition of pregnancy called preeclampsia.
• Toxicity: Oral LD50 in rats: 173 and 187 mg/kg
• Affected Organisms: Humans and other mammals
• Biotransformation: Hydralazine, when administered orally, undergoes extensive first-pass metabolism by genetic polymorphic acetylation, which is responsible for a threefold range of oral bioavailability. Intravenously administered hydralazine does not undergo first-pass metabolism and, therefore, is not affected by acetylator phenotype. After the drug reaches the systemic circulation, it is combined with endogenous aldehydes and ketones, including pyruvic acid, to form hydrazone metabolites. The active metabolites, hydralazine acetonide hydrazone and hydralazine pyruvate hydrazone, are equipotent with the parent, hydralazine.
• Absorption: Hydralazine is rapidly and extensively absorbed (up to 90%) from the gastrointestinal tract and undergoes extensive first-pass metabolism by genetic polymorphic acetylation. Oral bioavailability of hydralazine is dependent upon acetylator phenotype. Bioavailability is approximately 31% in slow acetylators and 10% in fast acetylators.
• Half Life: 3 to 7 hours
• Protein Binding: 87%
• Elimination: Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine.
• References: Kandler MR, Mah GT, Tejani AM, Stabler SN: Hydralazine for essential hypertension. Cochrane Database Syst Rev. 2010 Aug 4;8:CD004934. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

参考文献

• Kandler MR, Mah GT, Tejani AM, Stabler SN: Hydralazine for essential hypertension. Cochrane Database Syst Rev. 2010 Aug 4;8:CD004934. Pubmed