Synthesis and evaluation of new Reissert analogs as HIV-1 reverse transcriptase inhibitors. 1. Quinoline and quinoxaline derivatives.
The synthesis and preliminary evaluation of new quinoline and quinoxaline derivatives (obtained by applying the original Reissert method, conveniently modified) as HIV-1 Reverse Transcriptase (RT) inhibitors are presented in this paper; likewise, the first structure-activity relationships are also proposed. Propyl 2-cyano-1(2H)-quinolin-carboxylate 2e, isopropyl 2-cyano-1 (2H)-quinolincarboxylate 2f, butyl 2-cyano-1 (2H)-quinolincarboxylate 2g and isobutyl 2-cyano-1 (2H)-quinolincarboxylate 2h have been selected as lead compounds. These compounds are active against the HIV-1 RT mutant type P236L (2f, IC50 = 1.2 microM) and present activity as anti-infective agents in HLT41acZ-1IIIB cells, showing no cytotoxicity at the active concentrations.
Font
M
M
Medicinal Chemistry, Universidad de Navarra, Pamplona, Spain.
Monge
A
A
Alvarez
E
E
Cuartero
A
A
Losa
M J
MJ
Fidalgo
M J
MJ
SanMartín
C
C
Nadal
E
E
Ruiz
I
I
Merino
I
I
Martínez-Irujo
J J
JJ
Alberdi
E
E
Santiago
E
E
Prieto
I
I
Lasarte
J J
JJ
Sarobe
P
P
Borrás
F
F
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D011804:Quinolines; D011810:Quinoxalines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase