Fostedil (A-53,986, KB-944) is a vasodilator acting as a calcium channel blocker which was under development for the treatment of heart conditions such as

angina pectoris Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of obstru ...

but was never marketed. It has

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests tha ...

and

antiarrhythmic Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of pharmaceuticals that are used to suppress abnormally fast rhythms (Tachycardia, tachycardias), such as atrial fibrillation, supraventricular tachycardia and vent ...

effects.

Synthesis

#Treatment of benzanilide with

phosphorus pentasulfide Phosphorus pentasulfide is the inorganic compound with the formula (monomer) or (dimer). This yellow solid is the one of two phosphorus sulfides of commercial value. Samples often appear greenish-gray due to impurities. It is soluble in carbon d ...

Lawesson's reagent Lawesson's reagent (LR) is a chemical compound used in organic synthesis as a thiation agent. Lawesson's reagent was first made popular by Sven-Olov Lawesson, who did not, however, invent it. Lawesson's reagent was first made in 1956 during a s ...

gives

thioamide A thioamide (rarely, thionamide, but also known as thiourylenes) is a functional group with the general structure R–CS–NR′R″, where R, R′, and R″ are organic groups. They are analogous to amides but they exhibit greater multiple bond ch ...

. #Oxidative ring formation by reaction with

potassium ferricyanide Potassium ferricyanide is the chemical compound with the formula K3 e(CN)6 This bright red salt contains the octahedrally coordinated 3−.html" ;"title="e(CN)6sup>3−">e(CN)6sup>3− ion. It is soluble in water and its solution shows some g ...

and base (presumably involving a free radical intermediate) constructs the benzothiazole ring. #Bromination of this compound with

N-bromosuccinimide ''N''-Bromosuccinimide or NBS is a chemical reagent used in radical substitution, electrophilic addition, and electrophilic substitution reactions in organic chemistry. NBS can be a convenient source of Br•, the bromine radical. Preparatio ...

produces bromomethyl intermediate. #The synthesis of fostedil concludes with a Michaelis-Arbuzov reaction with

triethyl phosphite Triethyl phosphite is an organophosphorus compound with the formula P(OCH2CH3)3, often abbreviated P(OEt)3. It is a colorless, malodorous liquid. It is used as a ligand in organometallic chemistry and as a reagent in organic synthesis The molec ...

References

{{Calcium channel blockers Benzothiazoles Phosphonate esters

Synthesis

See also

References