As part of our research into new organic nitrates for the treatment of angina pectoris, we have investigated a series of hexitol and aminodeoxyhexitol mononitrate derivatives containing a sulfur group. Since the depletion of tissue stores of sulfhydryl groups appears to play an important role in the development of this phenomenon, the addition of a sulfur group to a nitrate derivative could prevent the development of nitrate tolerance during a long-term treatment. Before Organic nitrates, for example nitroglycerin, constitute the most widely used treatment for angina pectoris. Although not conclusively demonstrated [1] , it now seems well-documented that these compounds are transformed during the enzymatic or thiol-mediated metabolism as depicted in 933 studying the duration of action, and the possible influence on tolerance phenomenon, it was important to check the vasorelaxing effects of our compounds compared to those of commercial organic nitrates of similar structures such as isosorbide mononitrate or isosorbide dinitrate. All the compounds were tested on isolated rat aortas; some of these products exhibited an interesting activity.duces the development of tolerance which limits their efficiency. This has been explained by an intracellular depletion in thiol groups [7] . As it is known that the phenomenon can be avoided or reduced by simultaneous administration of -cysteine derivatives [8] [9] [10] , we have postulated that new compounds containing a nitrate moiety linked to cysteine, or masked cysteine, may provide the basis for structures devoid of tolerance development.For the design of new drugs, we have decided to combine the most easily obtained hexitol mononitrates 1, 2 and the aminodeoxyhexitol mononitrates 3, 4 with -cysteine derivatives (Figure 2). Due to the instability of the free SϪH group, protected or masked cysteines were used for the different syntheses.
As part of our research into new organic nitrates for the treatment of angina pectoris, we have investigated a series of hexitol and aminodeoxyhexitol mononitrate derivatives containing a sulfur group. Since the depletion of tissue stores of sulfhydryl groups appears to play an important role in the development of this phenomenon, the addition of a sulfur group to a nitrate derivative could prevent the development of nitrate tolerance during a long‐term treatment. Before studying the duration of action, and the possible influence on tolerance phenomenon, it was important to check the vasorelaxing effects of our compounds compared to those of commercial organic nitrates of similar structures such as isosorbide mononitrate or isosorbide dinitrate. All the compounds were tested on isolated rat aortas; some of these products exhibited an interesting activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.