Abstract
This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M5-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan Gq mAChR M1, M3, M5 PAM. An iterative library synthesis approach delivered the first selective M5 PAM (no activity at M1-M4 @ 30 μM), and an important tool compound to study the role of M5 in the CNS.
Original language | English (US) |
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Pages (from-to) | 558-562 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 20 |
Issue number | 2 |
DOIs | |
State | Published - Jan 15 2010 |
Externally published | Yes |
Keywords
- Allosteric
- M5
- Muscarinic receptor
- PAM
- Positive allosteric modualtor
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry