Synthesis and antiviral activity of carbocyclic oxetanocin analogues (C-OXT-A, C-OXT-G) and related compounds. II.
9-(cis-3-Hydroxymethyl-2-methylenecyclobutyl)guanine (3b) and 9-(3-methylene-trans-2-hydroxymethylcyclobutyl)guanine (4b) were prepared from N2-isobutyryl-9-[trans-trans-2,3-bis(hydroxymethyl)cyclobutyl]guanine (2f) or 2,3-bis(hydroxymethyl)-1-cyclobutanol (7b). Carbocyclic oxetanocin analogues (A, 1d; G, 2d) and related compounds including 4b were assayed against a broad variety of viruses. It appeared 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.
Department of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
T
T
Maruyama
Y
Y
Hanai
Y
Y
Sato
R
R
Snoeck
G
G
Andrei
M
M
Hosoya
J
J
Balzarini
E
E
De Clercq
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D010766:Phosphorylation; D018139:Simplexvirus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013937:Thymidine Kinase / Q000378:metabolism
D000998:Antiviral Agents; C062353:cyclobut A; D006147:Guanine; C063638:lobucavir; D013937:Thymidine Kinase; D000225:Adenine