[EN] SUBSTITUTED 6,7-DIALKOXY-3-ISOQUINOLINE DERIVATIVES AS INHIBITORS OF PHOSPHODIESTERASE 10 (PDE10A) [FR] DÉRIVÉS DE 6,7-DIALCOXY-3-ISOQUINOLINE SUBSTITUÉS À TITRE D'INHIBITEURS DE PHOSPHODIESTÉRASE 10 (PDE10A)
SUBSTITUTED 6, 7-DIALKOXY-3-ISOQUINOLINE DERIVATIVES AS INHIBITORS OF PHOSPHODIESTERASE 10 (PDE 10A)
申请人:Allergan, Inc.
公开号:US20150158895A1
公开(公告)日:2015-06-11
The invention relates to compounds of the formula
or a pharmaceutically acceptable salt thereof, wherein R′, R
1
through R
7
and Ar are as defined herein. These compounds are useful as inhibitors of phosphodiesterase 10 (PDE10A) which are useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type II diabetes, metabolic syndrome, glucose intolerance, pain and ophthalmic diseases.
Two novel ring-like rigid quinoline-amide ligands, 2-[2-(1,3-dioxolan-2-yl)quinolin-8-yloxy]-N-benzylacetamide (L-I) and 3-[2-(1,3-dioxolan-2-yl)quinolin-8-yloxy]-1,1-diphenylpropan-2-one (L-II), were designed to assemble the anion-responsive luminescent europium complexes. Crystallographic studies of the EuLI(NO3)(3) and EuLII(NO3)(3) revealed that the tetradentate ligands L-I and L-II cooperatively coordinated with Eu3+ ion and some available sites around central europium ions for guest anions were reserved in the complexes. The luminescent properties of the Eu(III) nitrate complexes in acetonitrile solutions were investigated. And the lowest triplet state energy levels of the ligands are well placed to allow energy transfer to the resonance level of Eu(III). At the same time, the luminescence titration experiments and the Job's plot analysis demonstrated the formation of 1:1 complexes in the solutions. The luminescence intensities at 616 nm were enhanced by addition of NO3- or Cl- anion to the mixed acetonitrile solutions of Eu(CF3SO3)(3) and the ligands. (C) 2010 Elsevier B.V. All rights reserved.