Literature

Abstract

A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3,4'-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC(50) values in the low double-digit nanomolar range against Akt1. Compound 2q shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to modest selectivity against closely related kinases in the AGC and CMGC families. The cellular activities including inhibition of cell growth and phosphorylation of downstream target GSK3 are also described. The X-ray structure of compound 2q complexed with PKA in the ATP binding site was determined.

DOI： 10.1016/j.bmcl.2005.12.017

Discovery of trans-3,4′-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation

Bioorganic & Medicinal Chemistry Letters 2006.0

Synthesis and structure–activity relationship of 3,4′-bispyridinylethylenes: Discovery of a potent 3-isoquinolinylpyridine inhibitor of protein kinase B (PKB/Akt) for the treatment of cancer

Bioorganic & Medicinal Chemistry Letters 2006.0

Discovery and SAR of oxindole–pyridine-based protein kinase B/Akt inhibitors for treating cancers

Bioorganic & Medicinal Chemistry Letters 2006.0

Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase

Bioorganic & Medicinal Chemistry Letters 2006.0

Discovery of a novel protein kinase B inhibitor by structure-based virtual screening

Bioorganic & Medicinal Chemistry Letters 2009.0

Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: Synthesis and SAR studies