Potent, orally absorbed glucagon receptor antagonists.
The SAR of 2-pyridyl-3,5-diaryl pyrroles, ligands of the human glucagon receptor and inhibitors of p38 kinase, were investigated. This effort resulted in the identification of 2-(4-pyridyl)-5-(4-chlorophenyl)-3-(5-bromo-2-propyloxyphenyl)pyrr ole 49 (L-168,049), a potent (Kb = 25 nM), selective antagonist of glucagon.
de Laszlo
S E
SE
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Hacker
C
C
Li
B
B
Kim
D
D
MacCoss
M
M
Mantlo
N
N
Pivnichny
J V
JV
Colwell
L
L
Koch
G E
GE
Cascieri
M A
MA
Hagmann
W K
WK
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; C118501:L 168049; D011725:Pyridines; D011758:Pyrroles; D018027:Receptors, Glucagon; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases