243467-56-3Relevant academic research and scientific papers
Discovery of novel α1-adrenoceptor ligands based on the antipsychotic sertindole suitable for labeling as PET ligands
Jorgensen, Morten,Jorgensen, Pernille N.,Christoffersen, Claus T.,Jensen, Klaus G.,Balle, Thomas,Bang-Andersen, Benny
, p. 196 - 204 (2013/02/22)
The synthesis and in vitro preclinical profile of a series of 5-heteroaryl substituted analogs of the antipsychotic drug sertindole are presented. Compounds 1-(4-fluorophenyl)-3-(1-methylpiperidin-4-yl)-5-(pyrimidin-5-yl)-1H- indole (Lu AA27122, 3i) and 1-(4-fluorophenyl)-5-(1-methyl-1H-1,2,4-triazol-3- yl)-3-(1-methylpiperidin-4-yl)-1H-indole (3l) were identified as high affinity α1A-adrenoceptor ligands with Ki values of 0.52 and 0.16 nM, respectively, and with a >100-fold selectivity versus dopamine D2 receptors. Compound 3i showed almost equal affinity for α1B- (Ki = 1.9 nM) and α1D- adrenoceptors (Ki = 2.5 nM) as for α1A, as well as moderate affinity for 5-HT1B (Ki = 13 nM) and 5-HT 6 (Ki = 16 nM) receptors, whereas 3l showed >40-fold selectivity toward all other targets tested. Based on in vitro assays for assessment of permeability rates and extent, it is predicted that both compounds enter the brain of rats, non-human primates, as well as humans, and as such are good candidates to be carried forward for further evaluation as positron emission tomography (PET) ligands.
5-heteroaryl substituted indoles
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, (2008/06/13)
The present invention relates to compounds having general formula (I) as defined herein, or a pharmaceutically acceptable acid addition salt thereof. The compounds are selective α1-adrenoceptor ligands.
