Design, synthesis, and evaluation of oxazole transthyretin amyloidogenesis inhibitors

…, ET Powers, HE Purkey, SL Adamski-Werner…

Index: Razavi, Hossein; Powers, Evan T.; Purkey, Hans E.; Adamski-Werner, Sara L.; Chiang, Kyle P.; Dendle, Maria T. A.; Kelly, Jeffery W. Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 4 p. 1075 - 1078

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Citation Number: 39

Abstract

Ten oxazoles bearing a C (4) carboxyl group were synthesized and evaluated as transthyretin (TTR) amyloid fibril inhibitors. Substituting aryls at the C (2) position of the oxazole ring reveals that a 3, 5-dichlorophenyl substituent significantly reduced amyloidogenesis. The efficacy of these inhibitors was enhanced further by installing an ethyl, a propyl, or a CF3 group at the C (5) position. The CF3 substitution at C (5) also ...