Sydnone Imines Research Articles

4 H-Thiopyrans bearing a mesoionic ring

The preparation of 4-(2,6-diamino-4H-thiopyran-3,5-dicarbonitrile) derivatives of sydnone and sydnone imines based on the ternary condensation of 4-formyl sydnones and sydnone imines with malononitrile and 2-cyanothioacetamide is reported.

4-Thio derivatives of sydnone imines

4-Thio derivatives of sydnone imines were obtained by the reaction of 4-lithiosydnone imines with elemental sulfur and subsequent treatment of the reaction mixture with electrophiles.

ChemInform Abstract: Synthesis and Reactivity of 4‐Lithium and 4‐Copper Derivatives of Sydnone Imines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis and reactivity of 4-lithium and 4-copper derivatives of sydnone imines

4-Lithium and 4-copper sydnone imines have been obtained, and preparative methods for the direct introduction of hydroxyalkyl, acyl, carbalkoxyl, vinyl and aryl groups into the 4-position of sydnone imines have been developed on this basis.

Heterocyclic NO prodrugs

An overview of the different heterocyclic NO-releasing compounds is given. Mesoionic heterocycles like sydnone imines are one example. This class is discussed on the synthesis and the mechanism of NO formation from Molsidomine and its first metabolite SIN-1. Furthermore, 1,2,3,4 oxatriazolium olates and imidates are presented in an example of the synthesis of GEA-3175. Heterocyclic N-oxides are another group of compounds capable of NO release under certain conditions. This class is discussed in the example of furoxane carboxamides like CAS-1609, and some SAR-data show the great impact of intramolecular hydrogen bridges on their in vitro activity. Each class of compounds requires different cofactors for NO release: sydnone imines need oxidants like oxygen, furoxanes are converted to NO via reaction with thioles.

New NO-donors with antithrombotic and vasodilating activities, V: Oligonitroso sydnone imines.

Nine 4,4'-bis- and four 4,4'-tris-N-nitroso syndrome imines were synthesized. The sydnone imine moiety is connected either by aromatic 1,3-phenylene or 1,3,5-benzene or aliphatic methylene or propylene bridges. Compared to the corresponding sydnone imines the collagen induced platelet aggregation inhibiting activity is increased by several orders of magnitude by the nitroso derivatives. The most potent compound bears a hexyl substituent in 3-position (1d: IC50 = 0.05 mumol/L). These data show that aromatic bridges (1d, 2d) are more favourable than aliphatic ones (4b). This indicates the mutual influence of the nitroso-imino moieties via the aromatic bridges. In the series of 3,3'-bis-nitrososydnone imines (13 compounds) mostly additive effects of the nitroso groups are seen. The activities range from IC50 = 0.2 mumol/L (5i; 1,3-xylene bridge) to IC50 = 8 mumol/L (5b; trimethylene bridge). The differences suggest different affinities to the platelet membrane.

New NO-donors with antithrombotic activities and vasodilating activities, III: 3,4-disubstituted N-nitroso-5-sydnone imines.

38 title compounds have been synthesized. They bear a wide variety in substituents including alkyl-, aryl-, arylalkyl-, and styryl groups. The anti-platelet activities elucidated in the Born-test with collagen cover more than two orders of magnitude (IC50 = 0.3-45 mumol/L). These effects depend on the presence of the N-NO-group. This is shown by comparison with the corresponding sydnone imines, sydnone cyanimines, and sydnones. The most suitable substituents were phenylethyl, styryl, and hexyl at either position of the molecule. Seven compounds, most of them styryl derivatives, have IC50 values below 1 mumol/L. It is suggested that the differences in activity are connected with the ability of the compounds to bind to the platelet membrane.

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XX: 4,4',4''-(1,3,5)-benzene-tris-sydnone imines.

The synthesis of ten tris-sydnone imine derivatives, unknown up to now, is described. All compounds are alkyl or arylalkyl substituted in 3-position of the sydnone imine. The most powerful agent was the 3-propyl derivative 6c. It inhibits the aggregation of human platelets induced by collagen in a concentration of 1 mumol/L half maximally. Its N-ethoxycarbonyl derivative 7c, which was designed as a prodrug, showed only small antithrombotic effects in rats. The reason for this low degree of activity is discussed.

Synthesis of a benzodiazepine analogous sydnotriazepine

AbstractStarting from 3‐benzylamino‐4‐benzoylsydnone (1) acylation to N‐acetyl (2a), N‐chloroacetyl (2b) and N‐bromoacetyl (2c) derivatives was successful. Treatment of 2b or 2c with liquid ammonia resulted in cleavage of the N‐acyl group to give sydnone imine 3 instead of cyclisation to sydnotriazepine 8. Condensation of 1 with protected glycines 5a‐5c by dicyclohexylcarbodiimide yielded glycineamides 6a, 6b and 6c. Compound 6c was selectively deprotected and converted to sydnotriazepine 7, a benzodiazepine analogous sydnotriazepine.

Solution Stability of Ciclosidomine

The stability of N-cyclohexanecarbonyl-3-(4-morpholino)-sydnone imine hydrochloride (ciclosidomine) in solution was studied as a function of pH, temperature, ionic strength, and buffer species. The rate of hydrolysis in the absence of light was found to be apparent first order in drug and general acid- and base-catalyzed reactions. The pH rate profile at an ionic strength of 0.1M at 60°C had a minimum value near pH 6. Change in ionic strength in the range of 0.05 to 0.2M did not affect the rate of degradation at pH 7 (carbonate buffer) or pH 2 (phosphate buffer) at 60°C. Similar degradation rates were noticed in air or nitrogen in the dark at pH 3, 5, and 6. However, degradation in light was very rapid in either case at pH 3, 5, and 6, and, therefore, the protection of solutions from light was required during all studies. The time for 10% loss of drug in solution at pH 6 in dilute phosphate or citrate buffer at an ionic strength of 0.154M was projected to be 9months at 20 ° and 2.6months at 30°C.

Metabolism of mesocarb in the rat

1. Rats treated orally with [14C]mesocarb (I; 3-(1-methyl-2-phenyl[2-(14C]ethyl)-N-(phenylaminocarbonyl)sydnone imine) (50 mg/kg) excrete 35% of the radioactivity in 24 h urine and 51% in 48 h urine. 2. Only traces of unchanged drug were found in urine. Hydroxy-mesocarb (II), dihydroxy-mesocarb (III), amphetamine (VII) and the conjugates of II and III account for 86% of the urinary radioactivity. 3. Cannulated male rats excrete about 40% of the radioactivity in 30 h in bile, mainly as conjugates of II and III.

ChemInform Abstract: KINETICS AND MECHANISM OF ACID CYCLIZATION OF N‐SUBSTITUTED N‐NITROSO‐α‐AMINOACETONITRILES INTO SYDNONE IMINES

Chemischer InformationsdienstVolume 8, Issue 19 Heterocyclic Compounds ChemInform Abstract: KINETICS AND MECHANISM OF ACID CYCLIZATION OF N-SUBSTITUTED N-NITROSO-α-AMINOACETONITRILES INTO SYDNONE IMINES V. V. OGORODNIKOVA, V. V. OGORODNIKOVASearch for more papers by this authorL. E. KHOLODOV, L. E. KHOLODOVSearch for more papers by this authorV. G. YASHUNSKII, V. G. YASHUNSKIISearch for more papers by this author V. V. OGORODNIKOVA, V. V. OGORODNIKOVASearch for more papers by this authorL. E. KHOLODOV, L. E. KHOLODOVSearch for more papers by this authorV. G. YASHUNSKII, V. G. YASHUNSKIISearch for more papers by this author First published: May 10, 1977 https://doi.org/10.1002/chin.197719211AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume8, Issue19May 10, 1977 RelatedInformation

Sydnone imines from ?-aminocaproic acid

Sydnone imines and their acyl derivatives have been synthesized from e-aminocaproic acid and its closest analogs. The possibility has been shown of the existence of internal salts in these sydnone imines and the impossibility of the formation of “betaine structures” in their acyl derivatives.

Sydnones and sydnonimines

For a number of sydnone imines with nonaryl substituents in position 3 the influence of structural factors on the kinetics of alkaline ring-opening has been studied and it has been found that the stability of the heterocycle falls with an increase in the electronegativity of the substituents. On passing from 3-aryl- to 3-nonaryl-substituted sydnone imines the mechanism of the reaction of alkaline ring-opening changes.

Sydnones and sydnone imines

For a number of sydnone imines with nonaryl substituents in position 3 the influence of structural factors on the kinetics of alkaline ring-opening has been studied and it has been found that the stability of the heterocycle falls with an increase in the electronegativity of the substituents. On passing from 3-aryl- to 3-nonaryl-substituted sydnone imines the mechanism of the reaction of alkaline ring-opening changes.

The influence of the nature of the substituents on the formation of the sydnone imine ring

The influence of the nature of the substituents on the formation of the sydnone imine ring

Molecular‐orbital calculations on some mesoionic compounds

AbstractMolecular‐orbital calculations have been performed on sydnone, sydnone imine, ψ‐oxatriazole, and isosydnone rings and their positive ionized forms by the Pariser–Parr–Pople–Brown–Heffernan method. The importance of elaborate open‐shell calculations and the effect of introducing nonneighbor core resonance integrals in this order of approximation are investigated. The available experimental data on closely related compounds are qualitatively in agreement with the calculated values. The computed charges and bond orders demonstrate that certain structural features are common to all five‐membered mesoionic ring systems and in agreement with recent experimental findings.

The Reaction of the Exo-cyclic Imino Group of “4-Thiazone Imine”

Abstract In order to accumulate further information about the properties of meso-ionic compounds -with an exo-cyclic imino group, the reactivity of an exo-cyclic imino group of thiazone imine as compared with that of sydnone imine was investigated. Moreover, for the purpose of the pharmacological test, 2,3-disubstituted thiazone imine hydrochlorides and their N-acetyl derivatives were prepared.

SYNTHESIS OF SYDNONES AND SYDNONE IMINES.

SYNTHESIS OF SYDNONES AND SYDNONE IMINES.

889. Formation and properties of sydnone imines, a new class of meso-ionic compound, and some sydnones related to natural α-amino-acids

889. Formation and properties of sydnone imines, a new class of meso-ionic compound, and some sydnones related to natural α-amino-acids