Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins
Research output: Contribution to journal › Journal article › Research › peer-review
This report describes the discovery and initial characterization of the first positive allosteric modulator of muscarinic acetylcholine receptor subtype 5 (mAChR5 or M5). Functional HTS, identified VU0119498, which displayed micromolar potencies for potentiation of acetylcholine at M1, M3, and M5 receptors in cell-based Ca(2+) mobilization assays. Subsequent optimization led to the discovery of VU0238429, which possessed an EC(50) of approximately 1.16 microM at M5 with >30-fold selectivity versus M1 and M3, with no M2 or M4 potentiator activity.
| Original language | English |
|---|---|
| Journal | Journal of Medicinal Chemistry |
| Volume | 52 |
| Issue number | 11 |
| Pages (from-to) | 3445-8 |
| Number of pages | 4 |
| ISSN | 0022-2623 |
| DOIs | |
| Publication status | Published - 11 Jun 2009 |
| Externally published | Yes |
- Allosteric Regulation/physiology, Animals, CHO Cells, Cricetinae, Cricetulus, Isatin/analogs & derivatives, Mice, Receptor, Muscarinic M5/drug effects
Research areas
ID: 213627227