Benzofuran based PDE4 inhibitors.
Replacement of the 3,4-dialkoxyphenyl substructure common to a number of PDE4 inhibitors with a 2-alkyl-7-methoxybenzofuran unit is described. This substitution can result in either enhancement or substantial reductions in PDE4 inhibitory activity depending on the system to which it is applied. An in vitro SAR study of a potent series of 4-(2-heteroaryl-ethyl)-benzoiurans 26 is also presented.
McGarry
D G
DG
Department of Medicinal Chemistry, Rhône Poulenc Rorer, Collegeville, PA 19426, USA.
Regan
J R
JR
Volz
F A
FA
Hulme
C
C
Moriarty
K J
KJ
Djuric
S W
SW
Souness
J E
JE
Miller
B E
BE
Travis
J J
JJ
Sweeney
D M
DM
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D019446:Endotoxemia / Q000139:chemically induced; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship
D001572:Benzofurans; D004791:Enzyme Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C105430:benzofuran