Identification and characterization of m4 selective muscarinic antagonists.
Our interest in the area of m4 muscarinic antagonists had led us to study a series of benzoxazine isoquinolines. One of the most potent and selective compounds of this series is example 1 with an IC50 value of 90.7 nM at m4 receptors, and 72-fold (m1), 38-fold (m2), 10-fold (m3), and 82-fold (m5) more selective compared to the other receptors. The synthesis and receptor binding affinity of analogs of 1 are reported.
Augelli-Szafran
C E
CE
Department of Medicinal Chemistry, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105, USA.
Jaen
J C
JC
Moreland
D W
DW
Nelson
C B
CB
Penvose-Yi
J R
JR
Schwarz
R D
RD
D007546:Isoquinolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
D007546:Isoquinolines; D018727:Muscarinic Antagonists; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic