Your browser doesn't support javascript.
loading
SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT).
Curtin, Michael L; Heyman, H Robin; Clark, Richard F; Sorensen, Bryan K; Doherty, George A; Hansen, T Matthew; Frey, Robin R; Sarris, Kathy A; Aguirre, Ana L; Shrestha, Anurupa; Tu, Noah; Woller, Kevin; Pliushchev, Marina A; Sweis, Ramzi F; Cheng, Min; Wilsbacher, Julie L; Kovar, Peter J; Guo, Jun; Cheng, Dong; Longenecker, Kenton L; Raich, Diana; Korepanova, Alla V; Soni, Nirupama B; Algire, Mikkel A; Richardson, Paul L; Marin, Violeta L; Badagnani, Ilaria; Vasudevan, Anil; Buchanan, F Greg; Maag, David; Chiang, Gary G; Tse, Chris; Michaelides, Michael R.
Afiliación
  • Curtin ML; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States. Electronic address: mike.curtin@abbvie.com.
  • Heyman HR; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Clark RF; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Sorensen BK; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Doherty GA; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Hansen TM; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Frey RR; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Sarris KA; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Aguirre AL; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Shrestha A; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Tu N; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Woller K; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Pliushchev MA; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Sweis RF; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Cheng M; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Wilsbacher JL; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Kovar PJ; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Guo J; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Cheng D; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Longenecker KL; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Raich D; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Korepanova AV; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Soni NB; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Algire MA; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Richardson PL; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Marin VL; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Badagnani I; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Vasudevan A; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Buchanan FG; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Maag D; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Chiang GG; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Tse C; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
  • Michaelides MR; AbbVie Inc, 1 North Waukegan Rd., North Chicago, IL 60064, United States.
Bioorg Med Chem Lett ; 27(15): 3317-3325, 2017 08 01.
Article en En | MEDLINE | ID: mdl-28610984
Herein we disclose SAR studies that led to a series of isoindoline ureas which we recently reported were first-in-class, non-substrate nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Modification of the isoindoline and/or the terminal functionality of screening hit 5 provided inhibitors such as 52 and 58 with nanomolar antiproliferative activity and preclinical pharmacokinetics properties which enabled potent antitumor activity when dosed orally in mouse xenograft models. X-ray crystal structures of two inhibitors bound in the NAMPT active-site are discussed.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Urea / Citocinas / Inhibidores Enzimáticos / Nicotinamida Fosforribosiltransferasa / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Urea / Citocinas / Inhibidores Enzimáticos / Nicotinamida Fosforribosiltransferasa / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido