Ishihara Sadao, Saito Fujio, Ohhata Yasuo, Kanai Marie, Mizuno Hiroshi, Fujisawa Michio, Yorikane Ryosuke, Koike Hiroyuki
Research Laboratories, Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140, Japan.
Bioorg Med Chem Lett. 2003 May 5;13(9):1527-30. doi: 10.1016/s0960-894x(03)00199-9.
To develop an orally active, long-acting nitrate that does not induce tolerance, nitroxyalkyl compounds were prepared and their activities evaluated by the use of carotid collaterals in anesthetized dogs. A compound having a favorable pharmacological profile, that is, long-lasting collateral vasodilatation and little hypotension, and lack of nitrate tolerance, was chosen for further evaluation.