Furegrelate, also known as 5-(3-pyridinylmethyl)benzofurancarboxylic acid, is a chemical compound with thromboxane enzyme inhibiting properties that was originally developed by Pharmacia Corporation as a drug to treat arrhythmias, ischaemic heart disorders, and thrombosis[1] but was discontinued.

Because of this Furegrelate is capable of preventing several diseases involving thrombosis, the occurrence of blood clots that block veins or arteries.

Currently no adverse effects of furegrelate are known due to a lack of research, although thromboxane A2 synthase devisentie could be a potential risk.

[2] Furegrelate in its free-base form is not well-soluble in pH-neutral aqueous environments and can therefore pass the lipophilic cell membranes.

Research also showed that pyridines substituted at the -3’ position with aryl or alkyl carboxylic acid groups, undergo a major enhancement of specifically TxA2 synthase inhibition, probably due to a more favourable molecular orientation during the reaction.

Several pathways were proposed for the synthesis of Furegrelate sodium salt and related compounds by Johnson et al. and is presented in Figure 1.

The hydroxyl group is obtained by stirring the diazo intermediate in a hot aqueous sulphuric acid solution, giving product 3.

Product 3 was formylated on the ortho-position relative to the hydroxyl group, using an adjusted Duff reaction using hexamine and trifluoroacetic acid (TFA).

Benzofuran-2-carboxylic acid ethyl ester (5), was obtained using a base-promoted reaction with diethyl bromomalonate and sodium hydride on product 4.

The compound plays a role in several diseases involving thrombosis, the occurrence of blood clots that block veins or arteries.

The absorption and disposition of the parent drug in male volunteers have been studied after single- and multiple-dose oral administration.

The results from the single-dose study indicate that furegrelate is rapidly absorbed in the blood, within maximally 1.0 to 1.7 hr.

[12] “Studies failed to detect major off-target effects in preclinical testing in dogs or in Phase 1 clinical trials using healthy adult human subjects.”[8] A possible adverse effect of furegrelate would be thromboxane synthase deficiency due to either too high of a dosage or due to too long administration.

However, this effect has not been studied yet, due to a lack of research in high dosage or long term administration of furegrelate.

[8] Furegrelate reduces renal vasoconstriction of angiotensin II, a blood pressure increasing hormone, in rats.