Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT)
Modification of the structure of trypanosomal AdoMetDC inhibitor 1 (MDL73811) resulted in the identification of a new inhibitor 7a, which features a methyl substituent at the 8-position. Compound 7a exhibits improved potencies against both the trypanosomal AdoMetDC enzyme and parasites, and better blood brain barrier penetration than 1.
Hirth, Bradford,Barker Jr., Robert H.,Celatka, Cassandra A.,Klinger, Jeffrey D.,Liu, Hanlan,Nare, Bakela,Nijjar, Amarjit,Phillips, Margaret A.,Sybertz, Edmund,Willert, Erin K.,Xiang, Yibin