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Design, synthesis and biological evaluation of a series of thioamides as non-nucleoside reverse transcriptase inhibitors.
Mehanna, Ahmed S; Belani, Jitendra D; Kelley, Charles J; Pallansc, Luke A.
Afiliación
  • Mehanna AS; Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy & Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115, USA. ahmed.mehanna@mcphs.edu
Med Chem ; 3(6): 513-9, 2007 Nov.
Article en En | MEDLINE | ID: mdl-18045200
A series of thioamides were designed as bio-isosteres to the non-nucleoside reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH groups with methylene groups. Eight thioamides were synthesized and in vitro tested for inhibitory effects on the activity of HIV-1 reverse transcriptase wild and mutant types. Three of the 8-thioamides exhibited enzyme inhibitory activities with IC(50) values below 100 microM. While compound (2) exhibited activity against the mutant strain L100I with IC(50) of 70.1 microM, compound (4) showed activity against the mutant strain K103N with IC(50) of 92.7 microM, and compound (8) with activity against the wild type enzyme with IC(50) of 8.9 microM. Each of the three thioamides could serve as a lead compound for further activity optimization.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tioamidas / Inhibidores de la Transcriptasa Inversa / Fármacos Anti-VIH / Transcriptasa Inversa del VIH Idioma: En Revista: Med Chem Asunto de la revista: QUIMICA Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tioamidas / Inhibidores de la Transcriptasa Inversa / Fármacos Anti-VIH / Transcriptasa Inversa del VIH Idioma: En Revista: Med Chem Asunto de la revista: QUIMICA Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos