HYPOTENSIVE ACTION OF N-ETHOXYCARBONYL-3-MORPHOLINOSYDNONIMINE, SIN-10

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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.<BR> 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.
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