Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-d]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-d]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study. (Articolo in rivista) (literal)

Anno

• 2011-01-01T00:00:00+01:00 (literal)

Alternative label

• Radi M, Dreassi E, Brullo C, Crespan E, Tintori C, Bernardo V, Valoti M, Zamperini C, Daigl H, Musumeci F, Carraro F, Naldini A, Filippi I, Maga G, Schenone S, Botta M. (2011)
  Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-d]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study.
  in Journal of medicinal chemistry
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Radi M, Dreassi E, Brullo C, Crespan E, Tintori C, Bernardo V, Valoti M, Zamperini C, Daigl H, Musumeci F, Carraro F, Naldini A, Filippi I, Maga G, Schenone S, Botta M. (literal)

Pagina inizio

• 2610 (literal)

Pagina fine

• 2626 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 54 (literal)

Rivista

• Journal of medicinal chemistry (Rivista)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• University of Siena, Italy University of Genova, Italy IGM-CNR, Pavia, Italy (literal)

Titolo

• Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-d]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study. (literal)

Abstract

• Abstract A family of dual Src/Abl inhibitors characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold was previously reported by us and proved to be active against several tumor cell lines. Among these compounds, a promising antileukemia lead (1) has been recently identified, but, unfortunately, it suffers from substandard pharmaceutical properties. Accordingly, an approach for the optimization of the lead 1 is described in the present work. A series of more soluble pyrazolo[3,4-d]pyrimidine derivatives were rationally designed and proved to maintain the dual Src/Abl activity of the lead. Selected compounds showed an interesting activity profile against three different leukemic cells also in hypoxic conditions, which are usually characterized by imatinib-resistance. Finally, in vitro ADME properties (PAMPA permeation, water solubility, microsomal stability) for the most promising inhibitors were also evaluated, thus allowing the identification of a few optimized analogues of lead 1 as promising antileukemia agents. (literal)

Prodotto di

• Sviluppo e meccanismo d'azione di analoghi nucleotidici e nucleosidici come composti antiproliferativi e antivirali : nuovi composti e nuovi bersagli per la terapia (ME.P04.004.001) (Modulo)
• Institute of molecular genetics (IGM) (Istituto)

Autore CNR

• GIOVANNI MAGA (Unità di personale interno)
• EMMANUELE CRESPAN (Persona)

Incoming links:

Prodotto

• Institute of molecular genetics (IGM) (Istituto)
• Sviluppo e meccanismo d'azione di analoghi nucleotidici e nucleosidici come composti antiproliferativi e antivirali : nuovi composti e nuovi bersagli per la terapia (ME.P04.004.001) (Modulo)

Autore CNR di

• GIOVANNI MAGA (Unità di personale interno)
• EMMANUELE CRESPAN (Persona)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Journal of medicinal chemistry (Rivista)