Discovery of hydroxamic acid analogs as dual inhibitors of phosphodiesterase-1 and -5

Akihito Dan; Takaaki Shiyama; Kazuto Yamazaki; Naoto Kusunose; Katsuya Fujita; Hideshi Sato; Kazutaka Matsui; Masafumi Kitano

doi:10.1016/j.bmcl.2005.06.016

Discovery of hydroxamic acid analogs as dual inhibitors of phosphodiesterase-1 and -5

Bioorg Med Chem Lett. 2005 Sep 15;15(18):4085-90. doi: 10.1016/j.bmcl.2005.06.016.

Authors

Akihito Dan¹, Takaaki Shiyama, Kazuto Yamazaki, Naoto Kusunose, Katsuya Fujita, Hideshi Sato, Kazutaka Matsui, Masafumi Kitano

Affiliation

¹ Research Division, Sumitomo Pharmaceuticals Co., Ltd, 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022, Japan.

PMID: 16005625
DOI: 10.1016/j.bmcl.2005.06.016

Abstract

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.

MeSH terms

Cyclic GMP / metabolism
Hydroxamic Acids / chemical synthesis
Hydroxamic Acids / chemistry*
Hydroxamic Acids / pharmacology*
Inhibitory Concentration 50
Molecular Structure
Phosphodiesterase Inhibitors / chemical synthesis*
Phosphodiesterase Inhibitors / chemistry
Phosphodiesterase Inhibitors / pharmacology*
Phosphoric Diester Hydrolases / metabolism*
Structure-Activity Relationship

Substances

Hydroxamic Acids
Phosphodiesterase Inhibitors
Phosphoric Diester Hydrolases
Cyclic GMP