当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Structure-activity relationship and properties optimization of a series of quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway.

Structure-activity relationship and properties optimization of a series of quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway.

Abstract：

:Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chemical properties of hit compound 1, our medicinal chemistry effort allowed the discovery and characterization of lead compound 33 (SEN461), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Nencini A,Pratelli C,Quinn JM,Salerno M,Tunici P,De Robertis A,Valensin S,Mennillo F,Rossi M,Bakker A,Benicchi T,Cappelli F,Turlizzi E,Nibbio M,Caradonna NP,Zanelli U,Andreini M,Magnani M,Varrone M

doi

10.1016/j.ejmech.2015.03.055

subject

Has Abstract

pub_date

2015-05-05 00:00:00

pages

526-45

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(15)00222-6

journal_volume

95

pub_type

杂志文章

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