Alkylated cAMP derivatives: selective synthesis and biological activities.
Many alkylated cAMPs have been prepared and tested for their antitumor and cardiac activities. Treatment of cAMP with several bases and alkyl bromides gave alkyltriesters of cAMP (2), N6,N6,2'-O-trialkyl cAMPs (3), N6,2'-O-dialkyl cAMPs (4) and 2'-O-monoalkyl cAMPs (5) in one step. N6,N6-dialkyl cAMPs (6) were prepared from 2'-O-tosyl cAMP by the similar alkylation, followed by detosylation. Synthesis of N6-monoalkyl cAMPs (7) was achieved by the reductive alkylation of cAMP with aldehydes in one step. Alkyl triesters of cAMP exhibited antitumor activities against P815 cells. N6-mono and N6,N6-dialkyl cAMPs showed significant cardiac activities.
Kataoka
S
S
Research and Development Division, Kikkoman Corporation, Chiba, Japan.
Imai
J
J
Yamaji
N
N
Kato
M
M
Saito
M
M
Kawada
T
T
Imai
S
S
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002316:Cardiotonic Agents / Q000138:chemical synthesis; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D051379:Mice
D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; D000242:Cyclic AMP