RADIOLABELLED QUINOLINE AND QUINOLINONE DERIVATIVES AND THEIR USE AS METABOTROPIC GLUTAMATE RECEPTOR LIGANDS

摘要

The present invention is concerned with radiolabelled quinoline and quinolinone derivatives according Formula (I-A)* or (I-B)* showing metabotropic glutamate receptor antagonistic activity, in particular mGlu1 receptor activity, and their preparation ; it further relates to compositions comprising them, as well as their use for marking and identifying metabotropic glutamate receptor sites and for imaging an organ. In a preferable embodiment, X represents O; Rrepresents Calkyl; cyclo-Calkyl or (cyclo-Calkyl)Calkyl, wherein one or more hydrogen atoms in a Calkyl-moiety or in a cycloC3-12alkyl-moiety optionally may be replaced by Calkyloxy, aryl, halo or thienyl; Rrepresents hydrogen; halo; Calkyl or amino; Rand Reach independently represent hydrogen or Calkyl; or Rand Rmay be taken together to form –R-R-, which represents a bivalent radical of formula –Z-CH-CH-CH- or - Z-CH-CH-CH- with Zbeing O or NRwherein Ris Calkyl; and wherein each bivalent radical is optionally substituted with Calkyl; or Rand Rmay be taken together to form a bivalent radical of formula - CH- CH- CH- CH- ; Rrepresents hydrogen; Y represents O; and aryl represents phenyl optionally substituted with halo. Most preferred are radiolabelled compounds in which the radioactive isotope is selected from the group ofH,C andF. The invention also relates to their use in a diagnostic method, in particular for marking and identifying a mGluR1 receptor in biological material, as well as to their use for imaging an organ, in particular using PET.