Synthesis and Antiviral Activity of Carbocyclic Oxetanocin Analogues(C-OXT-A, C-OXT-G) and Related Compounds. II

Abstract

9-(cis-3-Hydroxymethyl-2-methylenecyclobutyl)guanine (3b) and 9-(3-methylene-trans-2-hydroxymethylcyclobuty)guanine (4b) were prepared from N²-isobutyryl-9-[trans-trans-2, 3-bis(hydoxymethy)cyclobutyl]guanine (2f) or 2, 3-bis(hydroxymethy)-1-cyclobutanol (7b)- Carbocyclic oxetanocin analogues (A, 1d; G, 2d) and related compounds inclusing 4b were assayed against a broad variety of viruses. It apperred that the activity of 2d against herpes simplex virus(HSV) and varicella-zoster virus (VZV) at least partially depends on phosphorylation by the virus-induced thymidine kinase (TK). Although 1d and 2d are inhibitory to the replication of human immunodeficiency virus (HIV), they are quite toxic to proliferating human T-lymphocytes.