Discovery of hydroxamic acid analogs as dual inhibitors of phosphodiesterase-1 and -5.
HTS and the following synthesis of a series of the compounds led us to the discovery of hydroxamic acid analogs as potent dual inhibitors of phosphodiesterase (PDE)-1 and 5. These compounds have highly related structure and deviation of the structure usually resulted in reduced potency. This result can be used to design other molecules that may be utilized for the therapy of cardiovascular symptoms that relates to cGMP level.
Dan
Akihito
A
Research Division, Sumitomo Pharmaceuticals Co., Ltd, 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022, Japan.
Shiyama
Takaaki
T
Yamazaki
Kazuto
K
Kusunose
Naoto
N
Fujita
Katsuya
K
Sato
Hideshi
H
Matsui
Kazutaka
K
Kitano
Masafumi
M
D006152:Cyclic GMP / Q000378:metabolism; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006877:Hydroxamic Acids; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP