National Center for
4QT1: Jak3 Kinase Domain In Complex With 1-[(3s)-1-isobutylsulfonyl-3- Piperidyl]-3-(5h-pyrrolo[2,3-b]pyrazin-2-yl)urea
Scaffold hopping towards potent and selective JAK3 inhibitors: discovery of novel C-5 substituted pyrrolopyrazines
Bioorg. Med. Chem. Lett. (2014) 24 p.4969-4975
The discovery of a novel series of pyrrolopyrazines as JAK inhibitors with comparable enzyme and cellular activity to tofacitinib is described. The series was identified using a scaffold hopping approach aided by structure based drug design using principles of intramolecular hydrogen bonding for conformational restriction and targeting specific pockets for modulating kinase activity.