Design, synthesis, and evaluation of oxazole transthyretin amyloidogenesis inhibitors

Academic Article
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related to degree

  • Chiang, Kyle Ping, Ph.D. in Macromolecular and Cellular Structure and Chemistry, Scripps Research 2001 - 2006
  • Purkey, Hans, Ph.D. in Biology, Scripps Research 1996 - 2002

publication date

  • February 2005

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 CF(3) group at the C(5) position. The CF(3) substitution at C(5) also improves the TTR binding selectivity over all the other proteins in human blood.