Alfuzosin
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| Clinical data | |
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| Pronunciation | /ælˈfjuːzoʊsɪn/ al-FEW-zoh-sin |
| Trade names | Uroxatral, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a64002 |
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| Routes of administration | By mouth |
| Drug class | α1 blocker |
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| Pharmacokinetic data | |
| Bioavailability | 49% |
| Protein binding | 82–90% |
| Metabolism | Liver (CYP3A4-mediated) |
| Elimination half-life | 10 hours |
| Excretion | Feces (69%) and Urine (24%) |
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| ECHA InfoCard | 100.108.671 |
| Chemical and physical data | |
| Formula | C19H27N5O4 |
| Molar mass | 389.456 g·mol−1 |
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Alfuzosin, sold under the brand name Uroxatral among others, is a medication of the α1 blocker class. It is used to treat benign prostatic hyperplasia (BPH).[1]
As an antagonist of the α1-adrenergic receptor, it works by relaxing the muscles in the prostate and bladder neck, making urination easier.
Alfuzosin was patented in 1978 and approved for medical use in 1988.[2] It was approved in the US for benign prostatic hyperplasia in 2003. In 2020, it was the 336th-most commonly prescribed medication in the United States, with more than 700 thousand prescriptions.[3][4]
Side effects
[edit]The most common side effects are dizziness (due to postural hypotension), upper respiratory tract infection, headache, fatigue, and abdominal disturbances. Side effects include stomach pain, heartburn, and congested nose.[5] Adverse effects of alfuzosin are similar to that of tamsulosin, but with 70% lower rate of retrograde ejaculation.[6]
Chemistry
[edit]Alfuzosin contains a stereocenter, so is chiral, with two enantiomeric forms, (R)- and (S)-alfuzosin. The drug is used as a racemate, (RS)-alfuzosin, a 1:1 mixture of the (R)- and (S)- forms.[7]
| Enantiomers of alfuzosin | |
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-Alfuzosin_Structural_Formula_V2.svg) CAS number: 123739-69-5 |
-Alfuzosin_Structural_Formula_V2.svg) CAS number.: 123739-70-8 |
It is provided as the hydrochloride salt.
Society and culture
[edit]Brand names
[edit]It is sold under the brand names Alfosoft, Uroxatral,[8] Xatral, Prostetrol,[9] and Alfural.[10][unreliable source?]
Synthesis
[edit]The nitration of veratraldehyde [120-14-9] (1) gives 6-Nitroveratraldehyde [20357-25-9] (2). Oxidation of the aldehyde to the acid, halogenation with thionyl chloride and amide formation with ammonia gives 4,5-dimethoxy-2-nitrobenzamide [4959-60-8] (3). Béchamp reduction of the nitro group gives 2-amino-4,5-dimethoxybenzamide [5004-88-6] (4). Reaction with urea leads to 6,7-Dimethoxyquinazoline-2,4-dione [28888-44-0] (5). Halogenation with phosphoryl chloride gives 2,4-Dichloro-6,7-dimethoxyquinazoline [27631-29-4] (6). Treatment with one equivalent of ammonia yields 4-Amino-2-chloro-6,7-dimethoxyquinazoline [23680-84-4] (7).
The reaction of 2-Tetrahydrofuroic Acid [16874-33-2] (8) with Ethyl chloroformate [541-41-3] (9) gives Ethoxycarbonyl oxolane-2-carboxylate, PC10997775 (10). Treatment of the mixed anhydride with 3-Methylaminopropionitrile [693-05-0] (11) gives N-(2-Cyanoethyl)tetrahydro-N-methyl-2-furancarboxamide [72104-44-0] (12). Catalytic hydrogenation gives N-(3-Aminopropyl)tetrahydro-N-methyl-2-furancarboxamide [72104-45-1] (13). Migration of the amide methyl group to the terminal position gives N-[3-(methylamino)propyl]oxolane-2-carboxamide [81403-67-0] (14). Convergent synthesis between the two coutnerparts completed the synthesis of Alfuzosin (15).
References
[edit]- ^ Lepor H (August 2016). "Alpha-blockers for the Treatment of Benign Prostatic Hyperplasia". The Urologic Clinics of North America. 43 (3): 311–23. doi:10.1016/j.ucl.2016.04.009. PMC 2213889. PMID 27476124.
- ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 455. ISBN 9783527607495.
- ^ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
- ^ "Alfuzosin - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
- ^ "Alfuzosin". MedlinePlus. United States National Library of Medicine. 15 April 2016.
- ^ Liu C, Zeng G, Kang R, Wu W, Li J, Chen K, Wan SP (2015). "Efficacy and Safety of Alfuzosin as Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis". PLOS ONE. 10 (8): e0134589. Bibcode:2015PLoSO..1034589L. doi:10.1371/journal.pone.0134589. PMC 4526635. PMID 26244843.
This article incorporates text available under the CC BY 4.0 license.
- ^ Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 - Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, S. 159, ISBN 978-3-946057-10-9.
- ^ "Alfuzosin (Oral Route) Description and Brand Names - Mayo Clinic". www.mayoclinic.org. Retrieved 21 September 2022.
- ^ "Prostetrol 10mg 30 tablet". royalph.com. Retrieved 21 September 2022.
- ^ "Γαληνός - Φάρμακο - ALFURAL". www.galinos.gr (in Greek). Retrieved 21 September 2022.
- ^ Cazor, JL; Borg, F.; Dimsdale, M.; Alfuzosin hydrochloride. Drugs Fut 1986, 11, 10, 821.
- ^ Manoury, Philippe M.; Binet, Jean L.; Dumas, Andre P.; Lefevre-Borg, Francoise; Cavero, Icilio (1986). "Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives". Journal of Medicinal Chemistry 29 (1): 19–25. doi:10.1021/jm00151a003.
- ^ Philippe M. Manoury, US4315007 (1982 to Synthelabo SA); CA, 96, 162737e.
- ^ Keshav Deo, et al. WO2009001369 (to Alembic Ltd.).
- ^ Allen, J. (November 1983). "A synthesis of [ 14 C]alfuzosine hydrochloride". Journal of Labelled Compounds and Radiopharmaceuticals. 20 (11): 1283–1286. doi:10.1002/jlcr.2580201109.
