Abstract
Introduction of selected amine containing side chains into the 3-position of N′,2-diphenylquinoline-4-carbohydrazide based NK3 antagonists abolishes unwanted hPXR activation. Introduction of a fluorine at the 8-position is necessary to minimize unwanted hIKr affinity and a piperazine N-tert-butyl group is necessary for metabolic stability. The lead compound (8m) occupies receptors within the CNS following oral dosing (Occ90 7 mg/kg po; plasma Occ90 0.4 μM) and has good selectivity and excellent PK properties. © 2006 Elsevier Ltd. All rights reserved.
Original language | English |
---|---|
Pages (from-to) | 5752-5756 |
Number of pages | 4 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 16 |
Issue number | 22 |
DOIs | |
Publication status | Published - 15 Nov 2006 |
Keywords
- N′-2-Diphenylquinoline-4-carbohydrazide
- NK3
- Schizophrenia