Literature

Abstract

We report the discovery of 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(4-methylphenyl)-(E)-2,3,6,7-tetrahydro-1,4-thiazepine (2a) as an inducer of apoptosis using our proprietary cell- and caspase-based HTS assay. Through structure activity relationship (SAR) studies, 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-(2-methoxy-4-(methylthio)phenyl)-(E)-2,3,6,7-tetrahydro-1,4-thiazepine (5d) was identified as a potent apoptosis inducer with an EC(50) value of 0.08 microM in T47D cells, which was >15-fold more potent than screening hit 2a. Compound 5d also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.05 microM in T47D cells and to function as an inhibitor of tubulin polymerization.

DOI： 10.1016/j.bmcl.2007.05.098

Discovery of 5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-(E)-2,3,6,7-tetrahydro-1,4-thiazepines as a new series of apoptosis inducers using a cell- and caspase-based HTS assay

Bioorganic & Medicinal Chemistry Letters 2007.0

Discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers

Bioorganic & Medicinal Chemistry Letters 2009.0

Discovery of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as new apoptosis inducers using a cell- and caspase-based HTS assay

Bioorganic & Medicinal Chemistry Letters 2009.0

Discovery and structure–activity relationships of (2-(arylthio)benzylideneamino)guanidines as a novel series of potent apoptosis inducers

Bioorganic & Medicinal Chemistry 2009.0

Discovery of 4-Aryl-4H-chromenes as a New Series of Apoptosis Inducers Using a Cell- and Caspase-based High-Throughput Screening Assay. 1. Structure−Activity Relationships of the 4-Aryl Group

Journal of Medicinal Chemistry 2004.0

Discovery of Substituted N-Phenyl Nicotinamides as Potent Inducers of Apoptosis Using a Cell- and Caspase-Based High Throughput Screening Assay