1-hydrazinylphthalazine

• ChemBase ID: 1138
• Molecular Formular: C8H8N4
• Molecular Mass: 160.17592
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-hydrazinylphthalazine
• IUPAC Traditional name: hydralazine
• Brand Name: Apresoline
• Synonyms: Hydralazine hydrochloride; Hydralazine

Database IDs

• CAS Number: 86-54-4
• PubChem SID: 46507533; 160964601
• PubChem CID: 3637
• CHEBI ID: 5775
• ATC CODE: C02DB02
• CHEMBL: 276832
• Chemspider ID: 3511
• DrugBank ID: DB01275
• KEGG ID: D08044
• Unique Ingredient Identifier: 26NAK24LS8
• Wikipedia Title: Hydralazine
• Medline Plus: a682246

CALCULATED PROPERTIES

JChem

• Acid pKa: 17.691772
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): -0.19961534
• LogD (pH = 7.4): 0.7096126
• Log P: 0.7513803
• Molar Refractivity: 50.2348 cm^3
• Polarizability: 18.632671 Å^3
• Polar Surface Area: 63.83 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.66
• LOG S: -1.79
• Solubility (Water): 2.61e+00 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 0.7

Pharmacology Properties

• Admin Routes: Oral, intravenous
• Bioavailability: 26-55%
• Excretion: Renal
• Half Life: 2-4 hours
• Metabolism: Hepatic
• Pregnancy Category: C; Commonly used to treat severe PIH

DETAILS

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

REFERENCES

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