N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}oxolane-2-carboxamide

• ChemBase ID: 230
• Molecular Formular: C19H27N5O4
• Molecular Mass: 389.44878
• Monoisotopic Mass: 389.20630437
• SMILES: O1C(CCC1)C(=O)NCCCN(c1nc2c(c(n1)N)cc(OC)c(OC)c2)C
• Canonical SMILES: COc1cc2nc(nc(c2cc1OC)N)N(CCCNC(=O)C1CCCO1)C
• InChI: InChI=1S/C19H27N5O4/c1-24(8-5-7-21-18(25)14-6-4-9-28-14)19-22-13-11-16(27-3)15(26-2)10-12(13)17(20)23-19/h10-11,14H,4-9H2,1-3H3,(H,21,25)(H2,20,22,23)
• InChIKey: WNMJYKCGWZFFKR-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}oxolane-2-carboxamide
• IUPAC Traditional name: alfuzosin; N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}oxolane-2-carboxamide
• Brand Name: Uroxatral; Xatral
• Synonyms: Alfusosine; alfuzosin; Alfuzosin; Zatral; Alfoten; Mittoral; Urion; Alfuzosin

Database IDs

• CAS Number: 81403-80-7
• PubChem SID: 46508512; 160963693
• PubChem CID: 2092

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.639695
• H Acceptors: 8
• H Donor: 2
• LogD (pH = 5.5): -0.34812674
• LogD (pH = 7.4): 0.936928
• Log P: 1.1875362
• Molar Refractivity: 107.1141 cm^3
• Polarizability: 41.11549 Å^3
• Polar Surface Area: 111.83 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.02
• LOG S: -3.14
• Solubility (Water): 2.82e-01 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 1.4

Pharmacology Properties

• Mechanism of Action: alpha 1-Adrenoceptor antagonist

Product Information

• Application(s): Antihypertensive agent; Used in the treatment of benign prostatic hypertrophy

DETAILS

DrugBank - DB00346

• Drug Groups: approved; investigational
• Description: Alfuzosin (INN, provided as the hydrochloride salt) is an alpha-adrenergic blocker used to treat benign prostatic hyperplasia (BPH). It works by relaxing the muscles in the prostate and bladder neck, making it easier to urinate. [Wikipedia]
• Indication: For the reduction of urinary obstruction and relief of associated manifestations (eg. sensation of incomplete bladder emptying or straining, urgency, interrupted or weak stream) in patients with symptomatic beningn prostatic hyperplasia.
• Pharmacology: Alfuzosin is a quinazoline-derivative alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, alfuzosin is a selective inhibitor of the alpha(1) subtype of alpha adrenergic receptors. In the human prostate, alfuzosin antagonizes phenylephrine (alpha(1) agonist)-induced contractions, in vitro, and binds with high affinity to the alpha1a adrenoceptor, which is thought to be the predominant functional type in the prostate. Studies in normal human subjects have shown that alfuzosin competitively antagonized the pressor effects of phenylephrine (an alpha(1) agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of alfuzosin results from a decrease in systemic vascular resistance and the parent compound alfuzosin is primarily responsible for the antihypertensive activity.
• Toxicity: Side effects are dizziness (due to postural hypotension), upper respiratory tract infection, headache, and fatigue.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Alfuzosin undergoes extensive metabolism by the liver, with only 11% of the administered dose excreted unchanged in the urine. Alfuzosin is metabolized by three metabolic pathways: oxidation, O-demethylations, and N-dealkylation. The metabolites are not pharmacologically active. CYP3A4 is the principal hepatic enzyme isoform involved in its metabolism.
• Absorption: Absorption is 50% lower under fasting conditions
• Half Life: 10 hours
• Protein Binding: 82%-90%
• Elimination: Following oral administration of 14C-labeled alfuzosin solution, the recovery of radioactivity after 7 days (expressed as a percentage of the administered dose) was 69% in feces and 24% in urine.
• Distribution: * 3.2 L/kg [healthy male middle-aged volunteers]
• References: McKeage K, Plosker GL: Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62(4):633-53. [Pubmed] ; Wilde MI, Fitton A, McTavish D: Alfuzosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia. Drugs. 1993 Mar;45(3):410-29. [Pubmed] ; Andersson KE, Lepor H, Wyllie MG: Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate. 1997 Feb 15;30(3):202-15. [Pubmed] ; Elhilali MM: Alfuzosin: an alpha1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Expert Opin Pharmacother. 2006 Apr;7(5):583-96. [Pubmed] ; Roehrborn CG: Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001 Dec;58(6 Suppl 1):55-63; discussion 63-4. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• McKeage K, Plosker GL: Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62(4):633-53. Pubmed
• Wilde MI, Fitton A, McTavish D: Alfuzosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia. Drugs. 1993 Mar;45(3):410-29. Pubmed
• Andersson KE, Lepor H, Wyllie MG: Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate. 1997 Feb 15;30(3):202-15. Pubmed
• Elhilali MM: Alfuzosin: an alpha1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Expert Opin Pharmacother. 2006 Apr;7(5):583-96. Pubmed
• Roehrborn CG: Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001 Dec;58(6 Suppl 1):55-63; discussion 63-4. Pubmed
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• Wilde, M.I. et al., Drugs, 1993, 45, 410, (rev)
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