JAK1/TYK2-selective dual kinase inhibitor
oral activity in arthritis model
from SBDD of prior internal matter
Bioorg. Med. Chem. Lett., Mar. 31, 2020
Pfizer, Cambridge, MA and Groton, CT
“Compound 19” is a JAK1/TYK2 dual kinase inhibitor from Pfizer, related to its clinical JAK1/TYK2 dual inhibitor, brepocitinib, in Ph. II for a variety of inflammatory diseases. The cyclopropyl amide group was designed to displace a high energy water molecule. It was probably fortunate for their manufacturing colleagues that brepocitinib was taken forward instead, as the [3.1.0] core of this molecule was prepared through a Ti-mediated cyclopropanation in <20% yield.