2-[4-(2,3-dihydro-1,4-benzodioxine-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine

• ChemBase ID: 472
• Molecular Formular: C23H25N5O5
• Molecular Mass: 451.4751
• Monoisotopic Mass: 451.18556893
• SMILES: O1C(C(=O)N2CCN(CC2)c2nc3c(c(n2)N)cc(OC)c(OC)c3)COc2c1cccc2
• Canonical SMILES: COc1cc2nc(nc(c2cc1OC)N)N1CCN(CC1)C(=O)C1COc2c(O1)cccc2
• InChI: InChI=1S/C23H25N5O5/c1-30-18-11-14-15(12-19(18)31-2)25-23(26-21(14)24)28-9-7-27(8-10-28)22(29)20-13-32-16-5-3-4-6-17(16)33-20/h3-6,11-12,20H,7-10,13H2,1-2H3,(H2,24,25,26)
• InChIKey: RUZYUOTYCVRMRZ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[4-(2,3-dihydro-1,4-benzodioxine-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
• IUPAC Traditional name: 2-[4-(2,3-dihydro-1,4-benzodioxine-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine; doxazosin
• Brand Name: Alfadil; Cardenalin; Cardular; Cardura; Cardura-1; Cardura-2; Cardura-4; Carduran; Diblocin; Normothen; Supressin; Cardura XL
• Synonyms: Doxazosin mesilate; Doxazosin mesylate; Doxazosin; 2-[4-(2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine

Database IDs

• CAS Number: 74191-85-8
• MDL Number: MFCD00800482
• PubChem SID: 160963935; 46506825
• PubChem CID: 3157

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.670158
• H Acceptors: 9
• H Donor: 1
• LogD (pH = 5.5): 0.6322931
• LogD (pH = 7.4): 1.9103665
• Log P: 2.135759
• Molar Refractivity: 121.6383 cm^3
• Polarizability: 46.96491 Å^3
• Polar Surface Area: 112.27 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.53
• LOG S: -2.76
• Solubility (Water): 7.90e-01 g/l

PROPERTIES

Physical Property

• Solubility: 24 mg/L
• Melting Point: 279 - 281°C
• Hydrophobicity(logP): 2.1; 3.532

Product Information

• Purity: 95%

DETAILS

DrugBank - DB00590

• Drug Groups: approved
• Description: Doxazosin is a quinazoline-derivative that selectively antagonizes postsynaptic α₁-adrenergic receptors. It may be used to mild to moderate hypertension and in the management of symptomatic benign prostatic hyperplasia (BPH). α₁-Receptors mediate contraction and hypertrophic growth of smooth muscle cells. Antagonism of these receptors leads to smooth muscle relaxation in the peripheral vasculature and prostate gland.
• Indication: For treatment and management of mild to moderate hypertension and urinary obstruction symptoms caused by BPH.
• Pharmacology: Doxazosin is an alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, Doxazosin is a selective inhibitor of the alpha1 subtype of alpha adrenergic receptors. In the human prostate, Doxazosin antagonizes phenylephrine (alpha1 agonist)-induced contractions, in vitro, and binds with high affinity to the alpha1c adrenoceptor, which is thought to be the predominant functional type in the prostate. Studies in normal human subjects have shown that Doxazosin competitively antagonized the pressor effects of phenylephrine (an alpha1 agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of Doxazosin results from a decrease in systemic vascular resistance and the parent compound Doxazosin is primarily responsible for the antihypertensive activity.
• Toxicity: Symptoms of overdose include hypotension. Oral LD₅₀ is greater than 1000 mg/kg in mice and rats.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic.
• Absorption: 65%
• Half Life: 22 hours
• Protein Binding: 98%
• Elimination: On average only 4.8% of the dose was excreted as unchanged drug in the feces and only a trace of the total radioactivity in the urine was attributed to unchanged drug.
• References: Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM: Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM: Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404. Pubmed