N-Cyan-thiolimidoester und N,N′-Dicyan-amidine

N-Cyano-thiolimido Esters and N,N′-Dicyano-amidines Cyanamide ( 1 ) reacts with equimolar amounts of dithiocarbonate or xanthogenate esters 3 in the prescence of potassium methoxide to form potassium N-cyano-thiolimidates 4 , which have been alkylated to the N-cyano-thiolimido esters 5. Under similar conditions the thionoesters 8 always condense with 2 moles cyanamide ( 1 ) to yield the potassium N,N′-dicyanoamidines 9 . A possible reaction mechanism is proposed. Alkylation of 4 with chloro acetonitrile, chloroacetophenone and ethyl chloroacetate leads to the 4 -amino-thiazoles 12 .     

Formation of optically pure N-acyl-N,N′-dicyclohexylurea in N,N′-dicyclohexylcarbodiimide-mediated peptide synthesis

N-acylurea, a side product in peptide synthesis from DCC, preserves its chiral integrity although peptides formed simultaneously in the same reaction are racemized to a large extent. This observation is inconsistent with the generally accepted opinion that racemization-prone O-acylisourea is a common intermediate for both peptides and N-acylurea. Chiral purity of N-acylureas and peptides was determined by HPLC using chiral stationary phases. An efficient method of synthesis of chirally pure N-acylureas is also presented.     

Nitroketenaminale, 11. Mitt.: Zur Umsetzung von Enonen mit N,N′-cyclisch alkylierten Nitroketenaminalen

Nitroketeneaminals, XI: Reaction of Enones with N,N′-Cyclically Alkylated Nitroketeneaminals Reaction of enones 2a - d with nitroketeneaminals 3 , 4 , and 5 in refluxing ethanol yields the Michael adduct 8a and the bicyclic carbinolamines 9, 10 , and 11 . Dehydratisation of 9a - d in acidic medium leads to heteroanellated 1,4-dihydropyridines 12a-d . By means of ¹H-NMR-data the relative configuration of 10d is determined.     

Nucleophile Addition von N,N′-Dimethylbenzamidin an aktivierte Doppelbindungen

Nucleophilic Addition of N,N′-Dimethylbenzanmidine to Activated Double Bonds Reaction of (ethoxymethylene)malodinitrile ( 1 ) with N,N′-dimethylbenzamidine ( 4 ) leads primarily to the formation of the zwitterionic 2 : 1 adduct 5 , which rearranges in boiling ethanol to yield the uncharged structural isomer 6 . In boiling methanol compound 7 is formed. The structures of 5,6 and 7 were determined by ¹H-NMR and ¹³C-NMR spectroscopy. N,N′-dimethylbenzamidine ( 4 ) reacts with ethyl propiolate ( 13 ) to yield the Michael adduct 14 .     

SCF-MO study of the polyhydration of N,N′ -dimethylmalonamide

The effect of hydration on the conformation of the N,3 nylons has been studied using AM1 SCF-MO on the model molecule N,N′-dimethylmalonamide (NNMA). The polyhydration model has been used, so that only the water molecules directly bonded to solute molecule are considered. The study reveals that, although hydration induces dramatic changes in the torsional angles of the molecule, the new conformation still remains in the helical region of the Ramachandran map.     

Chemical and Electrochemical Synthesis of Some Substituted N,N′-Diacyl-p-phenylenediamines

Some N,N′-diacyl-p-phenylenediamines substituted with halogens ( 2a - c ) were prepared. Their polarographic reduction in N,N-dimethylformamide with Et₄NClO₄ was performed and discussed. The mechanism of the electrochemical reduction is stated. Large-scale electrolytic reductions of 2a - b to 3a - b were performed.     

Melaminderivate aus N′-Cyano-S,S′-dimethyl-guanidinodithioimidocarbonat

Melamine Derivatives from S,S'-Dimethyl N'-Cyanoguanidinodithioimidocarbonate The reaction of S,S'-dimethyl N'-cyanoguanidinodithioimidocarbonate with primary amines yields melamine derivatives by spontaneous cyclization instead of the expected cyanobiguanides. The compounds 9a–c showed no H₂-antihistaminic activity.     

Preparations,solution conformations and molecular structures of N,N′-ethylene-bridged dipeptides and their derivatives

The solution conformations of novel dipeptides, methyl (2S, 3′S)-3-methyl-2-(2′-oxo-3′-isopropyl-1′-piperazinyl)-butanoate (EVV-OCH₃), methyl (2S, 3′S)-3-phenyl-2-(2′-oxo-3′-benzyl-1′-piperazinyl) propionate (EFF-OCH₃), and their derivatives (Boc-Gly-EW-OH, Boc-Gly-EVV-Gly-OH, and Boc-Gly-EFF-OH), were studied by ‘H NMR measurements and molecular mechanics calculations (1). The molecular structures of Boc-Gly-EVV-OH, Boc-Gly-EFF-OH, and the hydrochloride of EVV-OCH₃ were determined by X-ray analyses. The conformations of the piperazinone rings and the side chains of these oligopeptides were clarified.     

Synthesis of Some N,N′‐Diacylhydrazine Derivatives with Radical‐Scavenging and Antifungal Activity

A series of N,N′‐diacylhydrazines were prepared and their structures were confirmed by ¹H NMR, MS and FTICR‐MS. They were tested radical‐scavenging activity in vitro. The preliminary bioassays of title compounds showed that two compounds had excellent radical‐scavenging activity comparable with vitamin C, while the activity is highly relative to the substituents. Surprisingly, several compounds also exhibit favorable fungicidal activities. To further explore the comprehensive structure–activity relationships about the fungicidal activity, a three‐dimensional quantitative structure–activity relationship analysis using the method of comparative molecular field analysis was performed.     

Ringschlußreaktionen mit N-(Chlormethyl)carbimidoylchloriden, 2. Mitt. Umsetzungsprodukte mit N,N′-Dimethylthioharnstoff

Heterocyclisation Reactions with N-(Chloromethyl)carboximidoyl Chlorides, II: Reaction with N, N′-Dimethylthiourea N-(Chloromethyl)benzimidoyl chloride ( 1 ) and N, N′-dimethylthiourea ( 2 ) react to form the three isomeric triazine and thiadiazine derivatives 6 , 7 and 8 , which were separated by layer chromatography. Their structures were determined by ¹³C-NMR spectroscopy. The thiadiazine derivative 11 was isolated as a by-product. A mechanism is proposed for its formation.     

Crystal and Molecular Structure of N,N′-Bis(1-hydroxy-2-butyl)ethylenediamine Dihydrochloride

The structure of N,N′-bis(1-hydroxy-2-butyl)ethylenediamine dihydrochloride was determined by X-ray analysis.     

Die Reaktion von N.N′-Dihydroxyaminalen mit Isocyansäureestern Mitt. über Hydroxylamin-Derivate

Reaction of N.N′-Dihydroxyaminals with Isocyanates Reaction of 2 moles of isocyanates with N.N′-dihydroxyaminals ( 1 ) leads by means of N→O-rearrangement to 3 ; or to the carbamoylated hydroxylamines 5 and 6 ; or to 2.4-disubstituted 1.2.4-oxadiazolidone-(5) 4 as cycloaddition-product of isocyanate with methylene nitrone 8 .     

Synthesis,docking studies,and pharmacological evaluation of 5HT2C ligands containing the N′‐cyanoisonicotinamidine or N′‐cyanopicolinamidine nucleus

N′‐Cyanoisonicotinamidine and N′‐cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinities to the 5‐HT_1A, 5‐HT_2A, and 5‐HT_2C receptors were evaluated. Several of the newly synthesized compounds, tested by binding studies, showed nanomolar affinity at the 5‐HT_1A and 5‐HT_2C receptors and moderate or no affinity for other relevant receptors (D₁, D₂, α₁, and α₂). Compound 8e (K_i = 21.4 nM) was the most affine for the 5‐HT_2C receptor, showing, at the same time, a high selectivity with respect to the other receptors analyzed. Compounds 4a and 4c , instead, showed an interesting mixed 5‐HT_1A/5‐HT_2C activity with K_i values of 21.3/11.5 and 23.2/6.48 nM, respectively. The compounds with better affinity and selectivity binding profiles toward 5‐HT_2C ( 4a , 4c , 8b , and 8e ) were selected for further in vivo assays to determine their functional activity. Finally, to rationalize the obtained results, molecular docking studies were performed. The results of the pharmacological studies showed that compounds 4a , 8b , and 8e exerted antidepressant‐like effects and 4a and 8e revealed also significant anxiolytic properties. Among the developed derivatives, the most promising compound seems to be 4a , which displayed antipsychotic‐, antidepressant‐ and anxiolytic‐like properties. No side effects, like catalepsy, motor‐impairment or ethanol‐potentiating effects, were observed after the injection of the tested compounds.     

Propyl- und Isopropylderivate der 2, 2′-Hydrazopyrimidine Mitt. Kondensationen mit Hydrazin-N,N′-dicarbonsäure-diamidin

Propyl and Isopropyl Derivatives of 2,2′-Hydrazopyrimidines Condensation of hydrazine N,N′-dicarboxylic acid diamidine (I) with β-diketones (II) in aqueous alcoholic sodium hydroxide as reaction medium at room temperature leads to 2,2′-hydrazopyrimidines (III). The new substances have been characterized by the N,N′-diacetyl derivatives and the IR′ and NMR spectra.     

Hypolipidemic Activity and Toxicity of 3-Methoxy-N,N′-diaminophthalamide in Rodents

3-Methoxy-N,N′-diaminophthalamide was observed to be a potent hypolipidemic agent in rodents. Serum cholesterol and triglyceride levels in rats were significantly reduced as were lipid contents of the liver, small intestine, and aorta wall. VLDL and LDL cholesterol levels were significantly reduced. Unfortunately, HDL cholesterol levels were also markedly reduced. Furthermore, acute toxicity studies showed that the compound caused marked increases in serum CP kinase activity with doses of 40 and 100 mg/kg/day in mice. This is not a property of the 2,3-dihydrophthalazine-1,4-dione, the resultant product of the N,N′-diaminophthalamides. Apparently, closing the ring results in a safer compound with elevations in HDL cholesterol levels, a desirable characteristic in effective hypolipidemic agents.     

In vitro evaluation of apoptotic effect of bis(acetylacetonato‐k2 O,O′)(1,10‐phenanthroline‐k2 N,N′)Zn(II) complex

Phenanthroline derivatives have been reported as potential bioactive compounds because of their ability to interact with DNA . To evaluate the antiproliferative effect of bis (acetylacetonate‐k ² O,O )(1,10‐phenanthroline‐k ² N,N )Zn(II ) or Zn(acac)₂(phen) complex, the compound was obtained in a simple manner and further characterized to determine crystal structure, thermal behavior, morphology, and spectroscopic properties. The structure of the complex was confirmed by X‐ray single structure as well as by 1H and 13C nuclear magnetic resonance (NMR ) in dmso‐d6 (dimethyl sulfoxide) solution and in the solid state by 13C CP /MAS . Although preparation of this compound has been described previously, there are no reports on its biological activity; here, we assessed its antiproliferative effect on fibroblasts, A253, FaDu, Cal‐27, RH ‐30, RD , U‐373, C6, A‐549, MDA ‐MB ‐231, and MCF ‐7 cancer cell lines at different doses (50–100 and 150 μg/ml). The cell viability was determined by MTT assay and high activity was observed for the most of the cell lines, and TUNEL results showed the induction of apoptosis.