6msc
Novel, potent, selective and brain penetrant phosphodiesterase 10A inhibitorsNovel, potent, selective and brain penetrant phosphodiesterase 10A inhibitors
Structural highlights
Function[PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.[1] Publication Abstract from PubMedHerein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3. Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors.,Geneste H, Drescher K, Jakob C, Laplanche L, Ochse M, Torrent M Bioorg Med Chem Lett. 2018 Dec 19. pii: S0960-894X(18)30976-4. doi:, 10.1016/j.bmcl.2018.12.029. PMID:30587449[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||