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Updated: Dec 26, 2025

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Spiro-oxindole Piperidines and 3-(Azetidin-3-yl)-1H-benzimidazol-2-ones as mGlu2 Receptor PAMs
Ana Isabel de Lucas1, Juan Antonio Vega1, Encarnación Matesanz1
1Discovery Chemistry, Janssen Research & Development, Division of Janssen-Cilag S.A., Jarama 75A, Toledo 45007, Spain.
Abstract:
Starting from two weak mGlu2 receptor positive allosteric modulator (PAM) HTS hits (4 and 5), a molecular hybridization strategy resulted in the identification of a novel spiro-oxindole piperidine series with improved activity and metabolic stability. Scaffold hopping around the spiro-oxindole core identified the 3-(azetidin-3-yl)-1H-benzimidazol-2-one as bioisoster. Medicinal chemistry optimization of these two novel chemotypes resulted in the identification of potent, selective, orally bioavailable, and brain penetrant mGluR2 PAMs.
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