A reciprocal relationship exists between circadian disruption and psychiatric conditions such as bipolar disease, major depressive disorders, and schizophrenia. There is a growing body of evidence indicating that inhibitors of the kinase CK1 delta have the potential to restore and stabilize circadian rhythms in these disorders. To study this potential disease target, we identified potent, selective, and brain penetrant CK1 delta inhibitors and evaluated the ADME properties of select compounds. Presented here will be the optimization of early leads using structure-based drug design, multi-parameter optimization to improve exposure in the CNS, and the synthetic methods used to access key analogs.

Discovery of selective and brain penetrant casein kinase 1 (CK1) delta inhibitors for the treatment of circadian rhythm disorders

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.