(+-)-carbocyclic 5'-nor-2'-deoxyguanosine and related purine derivatives: synthesis and antiviral properties.
Beginning with 3-cyclopenten-1-ylamine hydrochloride, the 5'-nor derivatives of carbocyclic 2'-deoxyguanosine (2), 2'-deoxyadenosine (3), and 2,6-diaminopurine 2'-deoxyribofuranoside (4) have been prepared. These compounds were evaluated for antiviral potential versus herpes simplex virus, varicella-zoster virus, cytomegalovirus, vaccinia virus, vesicular stomatitis virus, and human immunodeficiency virus and found to lack activity. Also, compounds 2-4 were virtually nontoxic toward the host (human diploid fibroblast ESM and HEL) cells. These biological properties may be due to the inability of 2-4 to be phosphorylated to the requisite nucleotide level that is likely to be necessary for biological activity by correlation to carbocyclic 2'-deoxyguanosine (1), which possesses significant antiviral properties as a result of conversion to its 5'-triphosphate derivative.
Patil
S D
SD
Department of Chemistry, University of South Florida, Tampa 33620-5250.
Koga
M
M
Schneller
S W
SW
Snoeck
R
R
De Clercq
E
E
D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects; D003839:Deoxyadenosines / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D014645:Herpesvirus 3, Human / Q000187:drug effects; D015394:Molecular Structure; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014616:Vaccinia virus / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D000998:Antiviral Agents; D003839:Deoxyadenosines; C075251:carbocyclic 5'-nor-2'-deoxyguanosine; D015075:2-Aminopurine; C007300:2,6-diaminopurine; D003849:Deoxyguanosine