Design, synthesis and pharmacological evaluation of HIV-1 reverse transcriptase inhibition of new indolin-2-ones.
The design, synthesis and anti HIV-1 replication inhibition of 3-(cyclopropylethynyl)-3-hydroxy-indolin-2-ones, analogues of efavirenz (Sustivatrade mark), are described. Different substituted isatins were used to generate final products that contain pharmacophoric features for RT inhibition, such as the oxoindole and cyclopropylethynyl groups. The suitability of the indolin-2-one ring in the planned compounds in replacement to the benzoxazinone ring of efavirenz was proven, since compound 15 presented a greater activity than efavirenz against HIV-1 replication and was not significantly cytotoxic.
Departamento de Pesquisa e Desenvolvimento de Fármacos, Instituto de Tecnologia em Fármacos, Far-manguinhos/FIOCRUZ, Rua Sizenando Nabuco, 100 Manguinhos, Rio de Janeiro 21041-250, Brazil. boechat@far.fiocruz.br
Núbia
N
Boechat
W Bruce
WB
Kover
Vera
V
Bongertz
Mônica M
MM
Bastos
Nelilma C
NC
Romeiro
Maria L G
ML
Azevedo
Wagner
W
Wollinger
D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D048588:Benzoxazines; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003521:Cyclopropanes; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; C456900:indolin-2-one; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C098320:efavirenz