Alfuzosin
Template:Short description Template:Use dmy dates Template:Drugbox
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 700,000 prescriptions.[3][4]
Side effects
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
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 | |
|---|---|
| Strukturformel des (R)-Enantiomers CAS number: 123739-69-5 |
Strukturformel des (S)-Enantiomers CAS number.: 123739-70-8 |
-Alfuzosin_Structural_Formula_V2.svg){kind=link}
-Alfuzosin_Structural_Formula_V2.svg){kind=link}
It is provided as the hydrochloride salt.
Society and culture
Brand names
It is sold under the brand names Alfosoft, Uroxatral,[8] Xatral, Prostetrol,[9] and Alfural.[10]Script error: No such module "Unsubst".
Synthesis
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
<templatestyles src="Reflist/styles.css" />
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".Template:CC-notice
- ↑ 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, Template:ISBN.
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ 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.).
- ↑ Script error: No such module "Citation/CS1".
Script error: No such module "Check for unknown parameters".
Template:Drugs used in benign prostatic hypertrophy Template:Adrenergic receptor modulators Template:Portal bar