Sulfur antagonist

Sulfur-containing compounds such as alpha-lipoic acid, methylsulfonylmethane, glutathione, N-acetylcysteine and cysteine are effective against oxidative stress and cell damage caused by free radicals (Bray and Taylor 1993, Pollack et al. 1996). Alpha-lipoic acid increases the antioxidant potency of further antioxidants such as vitamins E and C (Kagan et al. 1992). The course of acute pancreatitis is dramatically impaired in cases of very low antioxidant status. Whereas the sulfur antagonist selenium reduced remarkably the death rate (Kulinski et al. 1995), methionine was also used successfully in the treatment of this disease (Uden et al. 1990). 

Tricyclic Antidepressants. Imipramine [50-49-7] (32), which was the first tricycHc antidepressant to be developed, is one of many useful psychoactive compounds derived from systematic molecular modifications of the antihistamine prometha2ine [60-87-7] (see Histamine and histamine antagonists). The sulfur atom of prometha2ine was replaced with an ethylene bridge and the dimethylamino group attached to an / -propyl group, rather than to an isopropyl one, of the side chain. The actual synthesis of (32) is typical of the compounds in this class (37). 

Mixtures of Toxicants, Polluted atmospheres are complex mixtures of many toxic and inert materials which may interact to increase or diminish plant injury. Menser and Heggestad (26) reported the first evidence of synergistic response when an ozone-susceptible tobacco strain was exposed to a mixture of ozone and sulfur dioxide. Other researchers have subsequently confirmed this response, but attempts to identify synergistic or antagonistic responses with other pollutants have been unsuccessful, although synergistic effects of NO2 and SO2 are suggested. 

Sulfur atom can act as a nucleophile or an electrophile in ring closure. Nucleophilic behavior can be seen in the hydrolysis of the H-2 receptor antagonist ranitidine 261, which gives thiazine 262 as the main product (Scheme 51) <1987J(P1)951>. 

Preparation of a somewhat more complex leukotriene antagonist begins by aldol condensation of the methyl carbanion from quinoline (29-1) with meta-phthalalde-hyde (29-2) to give the stilbene-like derivative (29-3) dimer formation is presumably inhibited by the use of excess aldehyde. Reaction of that product with A,A-dimethyl-3-mercaptopropionamide in the presence of hexa-methylsilazane affords the silyl ether (29-4) of the hemimercaptal. Treatment of that intermediate with ethyl 3-mercaptopropionate leads to the replacement of the silyl ether by sulfur and the formation of the corresponding thioacetal (29-5). Saponification of the ester group leads to the carboxylic acid and thus to verlukast (29-6) [33]. 

Of the thiatriazines, the 1,2,4,6-system has been the most studied. There has been particular interest in TV-alkyl-1,2,4,6-thiatriazine 1,1-dioxides because of their herbicidal, fungicidal, and histamine H2-antagonist activity (86TL123,87S170). The preparation of l-chloro-l,2,4,6-thiatriazines (576) by reaction of imidoylamidines (575) with an excess of sulfur dichloride was reported (80JOU1303). 

Ganellin et al. [23] have combined histamine or its sulfur analog with nitrogen containing heterocycles ( urea equivalent strategy) to prepare a unique series of potent H3 antagonists related to UCL 1283 16. Examples of compounds from these efforts are the pyridine 18 (K,= 17 nM) and UCL 1199 19 (Ki = 4.8 nM) (Figure 9). 

Stymiest, J.L., Mitchell, B.F., Wong, S., and Vederas, J.C. (2005) Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increase stability. Journal of Organic Chemistry, 70, 7799-7809. 

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