Further optimization of the biaryl amide series via extensively exploring structure-activity relationships resulted in potent and subtype selective M 1 agonists exemplified by compounds 9a and 9j with good rat PK properties including CNS penetration. Synthesis, structure-activity relationships, subtype selectivity for M1 over M2-5, and DMPK properties of these novel compounds are described.
- 2′ biaryl amides
- CNS-penetrant and orally bioavailable M1 agonist
- Subtype selective M1 agonist
- Subtype selective M1 muscarinic acetylcholine receptor agonist