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Development of a highly selective, orally bioavailable and CNS penetrant M1 agonist derived from the MLPCN probe

Evan P Lebois1, Gregory J Digby, Douglas J Sheffler

  • 1Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Bioorganic & Medicinal Chemistry Letters
|September 21, 2011
PubMed

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Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...