2. Academic Validation
  3. Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors

Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors

  • Bioorg Med Chem Lett. 2019 Feb 1;29(3):406-412. doi: 10.1016/j.bmcl.2018.12.029.
Hervé Geneste 1,  Karla Drescher 2,  Clarissa Jakob 3,  Loïc Laplanche 4,  Michael Ochse 2,  Maricel Torrent 3
Affiliations

Affiliations

  • 1 AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, D-67008 Ludwigshafen, Germany. Electronic address: herve.geneste@abbvie.com.
  • 2 AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, D-67008 Ludwigshafen, Germany.
  • 3 AbbVie, Structural Biology, IL 60064-6101, USA.
  • 4 AbbVie Deutschland GmbH & Co. KG, DMPK, D-67008 Ludwigshafen, Germany.
PMID: 30587449 DOI: 10.1016/j.bmcl.2018.12.029
Abstract

Herein 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.

Keywords

PDE10A; Phosphodiesterase; WEB-3.

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