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1,4‐Thienodiazepine‐2,5‐diones via MCR (I): Synthesis, Virtual Space and p53‐Mdm2 Activity
Author(s) -
Huang Yijun,
Wolf Siglinde,
Bista Michal,
Meireles Lidio,
Camacho Carlos,
Holak Tad A.,
Dömling Alexander
Publication year - 2010
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2010.00989.x
Subject(s) - chemical space , peptidomimetic , combinatorial chemistry , chemistry , drug discovery , scaffold , virtual screening , stereochemistry , computer science , biochemistry , programming language , peptide
1,4‐Thienodiazepine‐2,5‐diones have been synthesized via the Ugi‐Deprotection‐Cyclization (UDC) approach starting from Gewald 2‐aminothiophenes in a convergent and versatile manner. The resulting scaffold is unprecedented, cyclic, and peptidomimetic with four points of diversity introduced from readily available starting materials. In addition to eighteen synthesized and characterized compounds, a virtual compound library was generated and evaluated for chemical space distribution and drug‐like properties. A small focused compound library of 1,4‐thienodiazepine‐2,5‐diones has been screened for the activity against p53‐Mdm2 interaction. Biological evaluations demonstrated that some compounds exhibited promising antagonistic activity.