Camostat mesylate acts as a serine protease inhibitor, which is active against the enzyme transmembrane protease serine 2 (TMPRSS2) partially blocked SARS-CoV-2 S-driven entry into lungs cells and full inhibition was attained when camostat mesylate is used in combination with other drugs. Thus, this compound has an envisaged use as a repurposed drug for the treatment of COVID-19. Currently the drug is under Phase-II clinical trial for the treatment of COVID-19 patients

Synthesis of camostat mesylate through the synthesis of its key intermediates, namely 2-(Dimethylamino)-2-oxoethyl 2-(4-hydroxyphenyl) acetate (Int-I) and 4-Guanidinobenzoic acid hydrochloride (Int-II), starting from inexpensive and indigenously available raw materials. The process is clean giving excellent yield and purity of both the compounds, Int-I and Int–II. The synthesis of both Int-I and Int-II have been performed at 50 g batch and are ready at 100 g level with purity >99% each.

The coupling between Int-I and Int-II gives the tosylate salt of camostat which is subsequently converted into camostat mesylate. The synthesis of camostat mesylate in solid form with 96% purity (hplc) has been achieved and reproduced in several 1 g batches. Currently efforts are ongoing to scale up the synthesis in up to 25 g batches

Upon realization of 25 g batches with pharmaceutically relevant purity, identification of industry partner shall be explored.

Not done yet

Chloroacetyl chloride, N,N-dimethyl amine hydrochloride, 4-hydroxyphenylacetic acid, sodium hydroxide, potassium hydroxide, 4-aminobenzoic acid, cyanamide, Dicyclohexylcarbodiimide, p-toluenesulfonic acid, sodium bicarbonate, methanesulfonic acid

Not yet figured out; process steps uses conventional reaction chemistry set up

Process for 2-(Dimethylamino)-2-oxoethyl 2-(4-hydroxyphenyl) acetate (KSM for camostat mesylate)

Process for 4-Guanidinobenzoic acid hydrochloride

Process for camostat mesylate (API)