Discovery, optimization, and biological evaluation of 5-(2-(trifluoromethyl)phenyl)indazoles as a novel class of transient receptor potential A1 (TRPA1) antagonists.

@article{Rooney2014DiscoveryOA,
  title={Discovery, optimization, and biological evaluation of 5-(2-(trifluoromethyl)phenyl)indazoles as a novel class of transient receptor potential A1 (TRPA1) antagonists.},
  author={Lisa Rooney and Agn{\`e}s Vidal and Anne-Marie D'Souza and N. J. Devereux and Brian T Masick and Valerie Boissel and Ryan West and Victoria Head and Rowan Stringer and Jianmin Lao and Matt J. Petrus and Ardem Patapoutian and Maribel Hilo Nash and Natalie Stoakley and Moh Panesar and Jan Martin Verkuyl and Andrew M. Schumacher and H. Michael Petrassi and David C Tully},
  journal={Journal of medicinal chemistry},
  year={2014},
  volume={57 12},
  pages={
          5129-40
        }
}
A high throughput screening campaign identified 5-(2-chlorophenyl)indazole compound 4 as an antagonist of the transient receptor potential A1 (TRPA1) ion channel with IC50 = 1.23 μM. Hit to lead medicinal chemistry optimization established the SAR around the indazole ring system, demonstrating that a trifluoromethyl group at the 2-position of the phenyl ring in combination with various substituents at the 6-position of the indazole ring greatly contributed to improvements in vitro activity… CONTINUE READING