mGluR5 Negative Allosteric Modulators Overview: A Medicinal Chemistry Approach Towards a Series of Novel Therapeutic Agents
| Autor: | Robert Johannes Lütjens, Vincent Mutel, Bernard Ludwig, Beatrice Bonnet, Jean-Philippe Rocher, Emmanuel Le Poul, Christelle Bolea, Mark Epping-Jordan, Bessis Anne-Sophie, Sonia Poli |
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| Rok vydání: | 2011 |
| Předmět: |
Pyridines
Chemistry Metabotropic glutamate receptor 5 Chemistry Pharmaceutical Receptor Metabotropic Glutamate 5 Allosteric regulation General Medicine Receptors Metabotropic Glutamate Highly selective Medicinal chemistry Small molecule Structure-Activity Relationship Allosteric Regulation Heterocyclic Compounds Metabotropic glutamate receptor Drug Design Positron-Emission Tomography Drug Discovery Structure–activity relationship |
| Zdroj: | Current Topics in Medicinal Chemistry. 11:680-695 |
| ISSN: | 1568-0266 |
| Popis: | Allosteric modulators of metabotropic glutamate receptors (mGluR) subtypes 1-8 have been shown to offer a valid way to develop small molecule non aminoacid-like therapeutics that can be administered orally and that readily cross the blood-brain barrier. Allosteric modulators of glutamatergic receptors and in particular mGluR5 have emerged as a novel and highly desirable class of compounds for the treatment of central nervous system (CNS) disorders and peripheral disorders. This article provides medicinal chemistry highlights around the chemical classes of potent and highly selective mGluR5 negative allosteric modulators (NAMs) and their therapeutic potential. In addition, it describes the medicinal chemistry approach from the discovery to the clinical candidate selection of a new series of heteroaryl-butynylpyridines targeting mGluR5. The multiparametric optimization of the initial starting point which ended in the selection of potential clinical candidates combining the best pharmacophoric features is presented. The pharmacological properties are reported and support the interest of these agents for new therapeutic approaches. Furthermore, a summary of the diverse mGluR5 Positron Emission Tomography (PET) radioligands is reported. |
| Databáze: | OpenAIRE |
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