Synthesis and anti-HIV activity of 1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-one (TBO) derivatives. Truncated 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2( 1H)-on es (TIBO) analogues.
4,5,6,7-Tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1 H)-ones (TIBO), 1, have been shown to significantly inhibit HIV-1 replication, as reported in detail in our prior publications. Since our earlier reports, we have modified the TIBO structures 1 by removing the 5-membered ring of 1, generating 1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-ones (TBO), 4, a bicyclic series of compounds. Although compounds 4 possess modest activity when compared to TIBO analogues 1, they clearly demonstrated significant anti-HIV-1 activity.
Breslin
H J
HJ
Janssen Research Foundation, Spring House, PA 19477, USA.
Kukla
M J
MJ
Kromis
T
T
Cullis
H
H
De Knaep
F
F
Pauwels
R
R
Andries
K
K
De Clercq
E
E
Janssen
M A
MA
Janssen
P A
PA
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D001570:Benzodiazepinones; D007093:Imidazoles