Synthesis and antiviral activity of 3-substituted derivatives of 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purines, tricyclic analogues of acyclovir and ganciclovir.
9-[(2-Hydroxyethoxy)methyl]guanine (acyclovir, 1a) and 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, ganciclovir, 1b) were transformed to their respective tricyclic derivatives, 3-substituted 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purines 2b, 3a, and 3b. The 6-methyl-substituted compound 2b was obtained following reaction of 1b with bromoacetone. A two-step approach via 1-(2,2-diethoxyethyl) intermediates 4a,b was the most effective for the preparation of the derivatives unsubstituted in the appended ring (3a,b). The novel acyclonucleosides, in particular ganciclovir derivative 2b, proved markedly active against herpes simplex virus type 1 and 2, varicella-zoster virus, and cytomegalovirus.
Boryski
J
J
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan.
Golankiewicz
B
B
De Clercq
E
E
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003587:Cytomegalovirus / Q000187:drug effects; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007093:Imidazoles; D011687:Purines; C070459:3,9-dihydro-3-((1,3-dihydroxy-2-propoxy)methyl)-6-methyl-9-oxo-5H-imidazol(1,2-a)purine; D015774:Ganciclovir; D000212:Acyclovir