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

Bioorganic & medicinal chemistry letters 2005 Sep 15; 15(18):4085-90

Link to PubMed abstract

Dan A A, Shiyama T T, Yamazaki K K, Kusunose N N, Fujita K K, Sato H H, Matsui K K, Kitano M M

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

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.