{Reference Type}: Journal Article
{Title}: Discovery of N-alkyl-N-benzyl thiazoles as novel TRPC antagonists for the treatment of glioblastoma multiforme.
{Author}: Wang S;Li X;Hu Y;Wang L;Lv G;Feng Y;Sun Z;Cao Z;Liu Y;Wang H;
{Journal}: Eur J Med Chem
{Volume}: 265
{Issue}: 0
{Year}: 2024 Feb 5
{Factor}: 7.088
{DOI}: 10.1016/j.ejmech.2023.116066
{Abstract}: Glioblastoma multiforme represents a substantial clinical challenge. Transient receptor potential channel (TRPC) antagonists might provide new therapeutic options for this aggressive cancer. In this study, a series of N-alkyl-N-benzoyl and N-alkyl-N-benzyl thiazoles were designed and prepared using a scaffold-hopping strategy and evaluated as TRPC6 antagonists. This resulted in the discovery of 15g, a potent TRPC antagonist that exhibited suitable inhibitory micromolar activities against TRPC3, TRPC4, TRPC5, TPRC6, and TRPC7 and displayed noteworthy anti-glioblastoma efficacy in vitro against U87 cell lines. In addition, 15g featured an acceptable pharmacokinetic profile and exhibited better in vivo potency (25 mg/kg/d) than the frontline therapeutic agent temozolomide (50 mg/kg/d) in xenograft models. Taken together, the TRPC antagonist 15g represents a promising lead compound for developing new anti-glioblastoma agents.