Tryptophanyl phosphoramidates as prodrugs of synadenol and its E-isomer: synthesis and biological activity.
Phosphorotryptophanates 2c and 3c were synthesized and investigated as prodrugs of synadenol (2a) and its E-isomer 3a. The antiviral activity of 2c corresponds to parent analogue 2a but it is lower than that of phenylphosphoralaninate 2b. This may indicate an enzymatic cleavage of phosphorotryptophanate 2c to 2a before or after entering the host cells. The E-isomer 3c was effective only against EBV with parameters suggesting intracellular delivery of the respective phosphate. Compound 2c has a moderate but selective activity against solid tumors.
Wang
Ruifang
R
Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201-1379, USA.
Corbett
Thomas H
TH
Cheng
Yung-Chi
YC
Drach
John C
JC
Kern
Earl R
ER
Mitsuya
Hiroaki
H
Zemlicka
Jiri
J
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D003521:Cyclopropanes / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000187:drug effects; D006801:Humans; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives*; D014407:Tumor Cells, Cultured; D014780:Viruses / Q000187:drug effects
D000577:Amides; D000998:Antiviral Agents; D003521:Cyclopropanes; D010756:Phosphoric Acids; D011355:Prodrugs; C116544:synadenol; D014364:Tryptophan; C011067:phosphoramidic acid; D000225:Adenine