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Bioorg Med Chem Lett ; 20(12): 3545-9, 2010 Jun 15.
Article in English | MEDLINE | ID: mdl-20483599

ABSTRACT

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 M(1) over M(2-5), and DMPK properties of these novel compounds are described.


Subject(s)
Amides/chemical synthesis , Amides/pharmacokinetics , Hydrocarbons, Aromatic/chemical synthesis , Hydrocarbons, Aromatic/pharmacokinetics , Receptor, Muscarinic M1/agonists , Amides/pharmacology , Animals , Blood-Brain Barrier/metabolism , Central Nervous System/metabolism , Drug Discovery , Hydrocarbons, Aromatic/pharmacology , Molecular Structure , Rats , Structure-Activity Relationship , Tissue Distribution
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