5848-24-8Relevant academic research and scientific papers
Synthesis and analgesic activity evaluation of some agmatine derivatives
He, Hongxia,Liu, Mengjia,Zheng, Zhibing,Liu, Ying,Xiao, Junhai,Su, Ruibin,Hu, Chun,Li, Jin,Li, Song
, p. 393 - 402 (2007/10/03)
A series of N,N′-disubstituted-2-nitroethene-1,1-diamine and N,N′-disubstituted-N″-cyanoguanidine derivatives were prepared and evaluated for in vivo analgesic activity. The blood brain barrier (BBB) VolSurf model was used to predict the BBB permeation profiles of our synthesized compounds. Some compounds show both remarkable analgesic activity and good BBB permeation profiles, and these compounds might be developed for treatment of opioid tolerance and dependence.
Enzymic denitrosation of 1,3-dimethyl-2-cyano-1-nitrosoguanidine in rat liver cytosol and the fate of the immediate product S-nitrosoglutathione
Jensen, David E.,Belka, George K.
, p. 1279 - 1295 (2007/10/03)
The tumorigenicity of certain N-nirtosoguanidinium compounds is limited, in rodents, by the propensity of these agents to be detoxified by denitrosation. Previous studies have revealed that rodent glutathione transferase isoenzymes are capable of catalyzing this process, generating exclusively the denitrosated guanidinium compound and S-nitrosoglutathione (GSNO). Experiments considering the denitrosation of 1,3-dimethyh2-cyano-1- nitrosoguanidine (CyanoDMNG) in rat liver cytosol incubates are reported, with emphasis on the fate of GSNO. Incubates composed with equimolar CyanoDMNO and reduced glutathione (GSH) effected 100% denitrosation; the GSNO yield was less than expected as was the quantity of GSH consumed. When the anticipated 100% yield concentration of GSNO was applied to cytosol incubates, 20-0% of it rapidly disappeared. Nitrosated protein thiols accounted for 35% of the NO moiety released, nitrite ion 30%, and nitric oxide production was detectable. Concomitant with GSNO loss, GSH and oxidized glutathione (GSSG) were generated in yields similar to those detected in the CyanoDMNG/GSH incubates. Thus, the fate of GSNO in cytosol determines the yields of glutathione-based products, and the stoichiometry of the glutathione transferase reaction is demonstrated. In incubates composed with equimolar CyanoDMNG, GSH, and NADPH, denitrosation was again 100%, but GSNO yields were very low and residual GSH increased. Inclusion of NADPH in incubates containing the anticipated 100% yield concentration of GSNO resulted in rapid GSNO degradation, producing GSH and a detected but unidentified product; S-nitrosated protein, nitrite, and nitrate yields were minimal, nitric oxide production was abolished, and incubate response to a mercuric chloride/azo dye assay approached zero. The fate of the NO moiety consequent to this GSNO catabolism is presently unknown.
N-bis(methylthio)methylene derivatives. VII. Syntheses and reactions of synthetic equivalents of new 1,3-dipolar reagents using N- bis(methylthio)methylene derivatives
Tominaga,Ogata,Ueda,Kohra,Hosomi
, p. 1425 - 1434 (2007/10/03)
N-Cyano- or N-(p-toluenesulfonyl)-N'-(trimethylsilylmethyl)-S- methylisothioureas (3,4), readily prepared by reactions of S,S'-dimethyl N- cyano- (1a) and S,S'-dimethyl N-(p-toluenesulfonyl)- (1b) carbonimidodithioates with trimethylsilylmethylamine (2a), followed by N- alkylation, have been found to provide synthetic equivalents of iminoazomethine ylide. Treatment of these compounds with cesium fluoride in the presence of reactive heterodipolarophiles such as carbonyl compounds afforded 1,3-dipolar cycloadducts, 4,5-dihydro-2-iminooxazoles and 4,5- dihydro-2-iminothiazoles, via the 1,3-elimination of (methylthio)trimethylsilane. S-Methyl-S'-trimethylsilylmethyl N-cyano- (5a) and N-(p-toluene-sulfonyl)- (5b) carbonimidodithioates, also readily prepared from the corresponding 1a and 1b with (mercaptomethyl)trimethylsilane (2b), were used as new reagents for introducing a thioformaldehyde unit at a carbonyl carbon. Reactions of these compounds with aldehydes in the presence of cesium fluoride afforded thiiranes via the 1,3-dipolar cycloaddition of iminothiocarbonyl ylide to the C=O double bond. Reactions of 5 with dimethyl fumarate and maleate in the presence of cesium fluoride in acetonitrile gave 1,3-dipolar cycloadducts, dimethyl 2-(N-(p- toluenesulfonyl)imino)tetrahydrothiophene-3,4-dicarboxylates.
Antihypertensive acylpyrazines
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, (2008/06/13)
Acylpyrazines useful in the treatment of hypertension are disclosed.
MECHANISM OF H/D EXCHANGE AND VINYLIC SUBSTITUTION IN 2,2-DISUBSTITUTED NITROETHYLENE AND RELATED STUDIES
Sega, Alessandro,Toso, Roberto,Sunjic, Vitomir,Klasinc, Leo,Sabljic, Aleksandar,Srzic, Dunja
, p. 217 - 222 (2007/10/02)
Rate measurements for H/D exchange at the α-C atom of the nitroethylenic moiety in ranitidine, 2 (a histaminic H2-receptor antagonist with ulcerostatic activity), and in the model compounds 3a, 3b have revealed pseudo-first order, pH-dependent kinetics.These data have been interpreted in terms of an acid-catalysed intramolecular proton (deuterium) transfer within the nitrolic form of the compounds investigated with inversion of configuration at the carbon-carbon double bond.Qualitative studies of the rates of nucleophilic substitution at the vinylic β-C atom in 2,2-bismethylthio-1-nitroethylene (3a) and 2,2-bismethylthio-N-cyanoazomethine (4a) with methylamine, revealed inversion of the relative rates of the first and second substitution step.The result has been rationalized as due to a change from addition-elimination to β,γ-elimination-addition mechanism.HMO calculations of the ?-electron densities and ?-bond orders in 3a-3c and 4a-4c support this rationalization.
