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Optimization of an ether series of mGlu5 positive allosteric modulators: Molecular determinants of MPEP-site interaction crossover
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Oct2012, Vol. 22 Issue 20, p6481-6485. 5p. - Publication Year :
- 2012
-
Abstract
- Abstract: We report the optimization of a series of non-MPEP site metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs) based on a simple acyclic ether series. Modifications led to a gain of MPEP site interaction through incorporation of a chiral amide in conjunction with a nicotinamide core. A highly potent PAM, 8v (VU0404251), was shown to be efficacious in a rodent model of psychosis. These studies suggest that potent PAMs within topologically similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 22
- Issue :
- 20
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 82062711
- Full Text :
- https://doi.org/10.1016/j.bmcl.2012.08.043