Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2',3'-seco-3'-nor DCP and DCK analogues.
Eur J Med Chem
; 46(10): 4924-36, 2011 Oct.
Article
en En
| MEDLINE
| ID: mdl-21864952
ABSTRACT
In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1'-O-, 1'-S-, 4'-O- and 4'-substituted-2',3'-seco-3'-nor DCP and DCK analogues (8-37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1(NL4-3) and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22-24, and 32) exhibited potent anti-HIV activity with EC(50) values ranging from 0.93 to 1.93 µM and therapeutic index (TI) values ranging from 20 to 39. 1'-O-Isopropoxy-2',3'-seco-3'-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC(50) values of 0.47 and 0.88 µM, and TI of 96 and 51, respectively, against HIV-1(NL4-3) and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Alcanfor
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Cromonas
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VIH-1
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Fármacos Anti-VIH
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Lactonas
Límite:
Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article