New neplanocin analogues. 6. Synthesis and potent antiviral activity of 6'-homoneplanocin A1.
The design, synthesis, and antiviral activities of 6'-homoneplanocin A (HNPA, 3) and its congeners having nucleobases other than adenine, such as 3-deazaadenine (4), guanine (5), thymine (6), and cytosine (7), were described. Starting from the known cyclopentenone derivative 8, the optically active (mesyloxy)cyclopentene derivative 15 was prepared, which was condensed with nucleobases then deprotected to give target compounds 3-7. Of these compounds, HNPA showed an antiviral activity spectrum that was comparable to, and an antiviral specificity that was higher than, that of neplanocin A. HNPA proved particularly active against human cytomegalovirus, vaccinia virus, parainfluenza virus, vesicular stomatitis virus, and arenaviruses, which is compatible with an antiviral action targeted at S-adenosylhomocysteine hydrolase. HNPA appears to be a promising candidate drug for the treatment of these viruses.
Shuto
S
S
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Obara
T
T
Saito
Y
Y
Andrei
G
G
Snoeck
R
R
De Clercq
E
E
Matsuda
A
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006477:Arenaviruses, New World / Q000187:drug effects; D002417:Cattle; D002522:Chlorocebus aethiops; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006564:Herpesviridae / Q000187:drug effects; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects; D010849:Picornaviridae / Q000187:drug effects; D011817:Rabbits; D013329:Structure-Activity Relationship; D014035:Togaviridae / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects; D014709:Vero Cells / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
C100365:6'-homoneplanocin A; D000998:Antiviral Agents; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; C031096:neplanocin A; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine