Several novel analogues of the potent antitumor agent cyclopentenyl cytosine (CPE-C) were synthesized. The modifications consisted mainly in changes in the aglycon moiety with the intent to enhance antimetabolite activity. These changes included the preparation of the corresponding 3-deaza- and 5-azapyrimidine analogues which are known in the conventional riboside series to possess antimetabolic and antitumor activity. The first synthesis of a carbocyclic ketosugar nucleoside analogue was accomplished. The prototypic compound of this series is psicoplanocin A, which incorporates in one molecule the structural features of the antibiotics neplanocin A and psicofuranine. The corresponding cytosine and uracil analogues were also prepared. 3-Deazaneplanocin A, a compound previously synthesized in this laboratory and the best known inhibitor of S-adenosylhomocysteine hydrolase, was found to possess potent activity against the ebola virus.
