Development of a Scalable Manufacturing Process for AB-343 Drug Substance: A Potential Candidate for the Treatment of Coronavirus Infections

A scalable process for manufacturing of the anticoronavirus clinical candidate AB-343 has been developed. The lactam-containing subunit of the molecule was prepared using a novel synthetic route involving a nitro-Michael reaction and a rhodium-catalyzed nitro group hydrogenation followed by in situ translactamization sequence as a key transformation. The drug substance was assembled via sequential amide coupling and deprotection reactions, followed by a final dehydration of a primary amide to the corresponding nitrile using T3P. AB-343 drug substance was successfully manufactured on a multikilogram scale using this route, which was suitable for supporting IND-enabling studies and Phase I clinical development.