Abstract
A new chemical series was identified via high-throughput screening as having antiproliferative activity on DU-145 human prostate carcinoma cell line (hit compound potency - 2.9 microM). Medicinal chemistry optimization of two peripheral diversity vectors of the hit molecule, independently, led to SAR generalizations and identification of the 'best' moieties. The latter were merged in a single compound that exhibited an over 100-fold better potency than the hit compound. For the most potent compounds it was confirmed that the observed antiproliferative potency was not associated with the compounds' non-specific cytotoxicity.
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