Abstract
The studies on structure and action of 3-substituted sydnonimines and their ring-opened derivatives (1, 2) indicated that hypotensive action induced by the compounds was closely related to the chemical stabilities of their sydnonimine rings and ring-opened derivatives. That is, a ring-opened derivative of 3-morpholinosydnonimine hydrochloride (SIN-1), N-nitroso-N-morpholinoaminoacetonitrile (SIN-1A), is unstable but a rapidacting and very potent vasodilator comparable to nitroglycerin. On the other hand, N-nitroso-N-cyclohexylaminoacetonitrite is stable and proved to be inactive. SIN-1 has less rapid but longer hypotensive action than SIN-1A. The former is chemically stable to acid but suffers ring-opening in alkali, leading to the formation of the latter and to the release of NO ion (3). It was also revealed that N-acylation of imino group of sydnonimine greatly increased chemical stability (4) and resulted in gradually developing and prolonged hypotensive action as well as in decreased toxicity.
This paper mainly reports hemodynamic action of N-ethoxycarbonyl-3-morpholinosydnonimine SIN-10, one of the least toxic, mild- and long-acting N-acylated sydnonimines. SIN-10 is a white, crystalline substance with a molecular weight of 242.2 and a melting point of 140 to 141°C. It is soluble in water as a 1.45% solution at room temperature and has the following structural formula.
