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Discovery and Potency Optimization of 2‐Amino‐5‐arylmethyl‐1,3‐thiazole Derivatives as Potential Therapeutic Agents for Prostate Cancer
Author(s) -
Krasavin Mikhail,
Karapetian Ruben,
Konstantinov Igor,
Gezentsvey Yuri,
Bukhryakov Konstantin,
Godovykh Elena,
Soldatkina Olga,
Lavrovsky Yan,
Sosnov Andrei V.,
Gakh Andrei A.
Publication year - 2009
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200800201
Subject(s) - potency , chemistry , thiazole , cytotoxicity , prostate cancer , prostate , combinatorial chemistry , structure–activity relationship , stereochemistry , cancer cell lines , high throughput screening , small molecule , pharmacology , computational biology , cancer , biochemistry , cancer cell , in vitro , biology , medicine
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 μM). 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.