| Title : 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 - Bridges_2009_J.Med.Chem_52_3445 |
| Author(s) : Bridges TM , Marlo JE , Niswender CM , Jones CK , Jadhav SB , Gentry PR , Plumley HC , Weaver CD , Conn PJ , Lindsley CW |
| Ref : Journal of Medicinal Chemistry , 52 :3445 , 2009 |
|
Abstract :
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. |
| PubMedSearch : Bridges_2009_J.Med.Chem_52_3445 |
| PubMedID: 19438238 |
Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW (2009)
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
Journal of Medicinal Chemistry
52 :3445
Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW (2009)
Journal of Medicinal Chemistry
52 :3445