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Summary: Synthesis of GABAA Receptor Agonists and Evaluation of their r-Subunit Selectivity and
Orientation in the GABA Binding Site
Michaela Jansen,,,§,
Holger Rabe,|,
Axelle Strehle,|,§
Sandra Dieler,
Fabian Debus,|
Gerd Dannhardt,
Myles H. Akabas,,
*
and Hartmut Lu¨ddens|,
*
Department of Medicinal Chemistry and Department of Psychiatry, Johannes Gutenberg-UniVersity, Mainz, Germany, and Departments of
Physiology & Biophysics, Neuroscience and Medicine, Albert Einstein College of Medicine of YeshiVa UniVersity, Bronx, New York
ReceiVed December 13, 2007
Drugs used to treat various disorders target GABAA receptors. To develop R subunit selective compounds,
we synthesized 5-(4-piperidyl)-3-isoxazolol (4-PIOL) derivatives. The 3-isoxazolol moiety was substituted
by 1,3,5-oxadiazol-2-one, 1,3,5-oxadiazol-2-thione, and substituted 1,2,4-triazol-3-ol heterocycles with
modifications to the basic piperidine substituent as well as substituents without basic nitrogen. Compounds
were screened by [3
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