Alfuzosin, sold under the brand name Uroxatral among others, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

of the α₁ blocker class. It is used to treat

benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, urinary retention, inability t ...

(BPH). As an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.α₁-adrenergic receptor, it works by relaxing the muscles in the

prostate The prostate is an male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemica ...

and

bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the bladder is a distens ...

neck, making urination easier. Alfuzosin was patented in 1978 and approved for medical use in 1988. 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 700thousand prescriptions.

Side effects

The most common side effects are

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

(due to postural hypotension),

upper respiratory tract infection An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the nose, sinuses, pharynx, larynx or trachea. This commonly includes nasal obstruction, sore throat ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

, and abdominal disturbances. Side effects include stomach pain,

heartburn Heartburn is a burning sensation felt behind the breastbone. It is a symptom that is commonly linked to acid reflux and is often triggered by food, particularly fatty, sugary, spicy, chocolate, citrus, onion-based and tomato-based products. Ly ...

, and congested nose. Adverse effects of alfuzosin are similar to that of tamsulosin, but with 70% lower rate of

retrograde ejaculation Retrograde ejaculation occurs when semen which would be ejaculated via the urethra is redirected to the urinary bladder. Normally, the sphincter of the bladder contracts before ejaculation, inhibiting urination and preventing a reflux of semen ...

Chemistry

Alfuzosin contains a

stereocenter In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups cr ...

, so is

chiral Chirality () is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek language, Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is dist ...

, with two

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

ic forms, (''R'')- and (''S'')-alfuzosin. The drug is used as a

racemate In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

, (''RS'')-alfuzosin, a 1:1 mixture of the (''R'')- and (''S'')- forms.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, . It is provided as the hydrochloride salt.

Society and culture

Brand names

It is sold under the brand names Alfosoft, Uroxatral, Xatral, Prostetrol, and Alfural.

Synthesis

The nitration of veratraldehyde 20-14-9(1) gives 6-Nitroveratraldehyde 0357-25-9(2). Oxidation of the aldehyde to the acid, halogenation with thionyl chloride and amide formation with ammonia gives 4,5-dimethoxy-2-nitrobenzamide 959-60-8(3). Béchamp reduction of the nitro group gives 2-amino-4,5-dimethoxybenzamide 004-88-6(4). Reaction with urea leads to 6,7-Dimethoxyquinazoline-2,4-dione 8888-44-0(5). Halogenation with phosphoryl chloride gives 2,4-Dichloro-6,7-dimethoxyquinazoline 7631-29-4(6). Treatment with one equivalent of ammonia yields 4-Amino-2-chloro-6,7-dimethoxyquinazoline 3680-84-4(7). Alfuzosin synthesis

The reaction of 2-Tetrahydrofuroic Acid 6874-33-2(8) with Ethyl chloroformate 41-41-3(9) gives Ethoxycarbonyl oxolane-2-carboxylate, PC10997775 (10). Treatment of the mixed anhydride with 3-Methylaminopropionitrile 93-05-0(11) gives N-(2-Cyanoethyl)tetrahydro-N-methyl-2-furancarboxamide 2104-44-0(12). Catalytic hydrogenation gives N-(3-Aminopropyl)tetrahydro-N-methyl-2-furancarboxamide 2104-45-1(13). Migration of the amide methyl group to the terminal position gives N- -(methylamino)propylxolane-2-carboxamide 1403-67-0(14). Convergent synthesis between the two coutnerparts completed the synthesis of Alfuzosin (15).

References

{{Portal bar , Medicine , Viruses Alpha-1 blockers Carboxamides Quinazolines Tetrahydrofurans