Synthesis and antiviral activity of some 7-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine analogues of sangivamycin and toyocamycin.
The sodium salt of 4-amino-3-cyanopyrazolo[3,4-d]pyrimidine (1) was condensed with (2-acetoxyethoxy)methyl bromide (2) to provide the corresponding protected acyclic nucleoside, 4-amino-3-cyano-1-[(2-acetoxyethoxy)methyl]-pyrazolo[3,4-d]pyrimid ine (3). Treatment of 3 with sodium methoxide in methanol provided a good yield of methyl 4-amino-1-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine-3- formimidate (4). Treatment of the imidate (4) with sodium hydrogen sulfide gave the thiocarboxamide derivative 5. Aqueous base transformed 4 into 4-amino-1-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine-3- carboxamide (6) in good yield. Treatment of 5 with mercuric chloride furnished the toyocamycin analogue 7. Evaluation of compounds 1, 3-7 revealed that only the heterocycle (1) and the thiocarboxamide acyclic nucleoside (5) were active. Compound 5 was the more potent with activity against human cytomegalovirus and herpes simplex virus type 1.
Saxena
N K
NK
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Coleman
L A
LA
Drach
J C
JC
Townsend
L B
LB
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003587:Cytomegalovirus / Q000187:drug effects* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007202:Indicators and Reagents; D007624:KB Cells; D015394:Molecular Structure; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D014127:Toyocamycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D010948:Viral Plaque Assay
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D007202:Indicators and Reagents; D011741:Pyrimidine Nucleosides; C005699:sangivamycin; D014127:Toyocamycin