Synthesis, lipophilicity and anti-HIV activity of a new brominated analog of zidovudine.
A novel cyclic bromine zidovudine analog, (-)-trans-(5S,6S)-5-bromo-6,5'- epoxy-5,6-dihydro-3'-azido-3'-deoxythymidine (2), and its diastereoisomer (+)-trans-(5R,6R)-(3) were synthesized and characterized by spectroscopic methods, obtaining 3 in very low yields. The major product 2 presents a selectivity index (CCID50/IC50) similar to zidovudine but 55.5 times with higher lipophilicity, which should increase the ability of 2 to cross the blood-brain barrier by a non facilitated diffusion mechanism.
Motura
M
M
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Argentina.
Salomón
H
H
Moroni
G
G
Wainberg
M
M
Briñón
M C
MC
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004355:Drug Stability; D005312:Fetal Blood; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D013237:Stereoisomerism; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C119903:5-bromo-6,5'-epoxy-5,6-dihydro-3'-azido-3'-deoxythymidine; D019380:Anti-HIV Agents; D015215:Zidovudine