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2-Amino-4-dialkylamino- or -4-ethoxy-6-methylthio-5-pyrimidine- carbonitriles 3 are obtained through a base-induced reaction between 3-amino-3-(dialkylamino)propenenitriles 1 and N-[bis(methylthio)methylene]cyanamide (2)

The reaction of 2-cyanoacetamidines 1 with carbon suboxide 2 afforded 6-amino-4-hydroxy-2(1H)-pyri-dones 4. Compounds 4 were also obtained by reaction of amidines 1 and 2,4,6-trichlorophenylmalonates 3.

3-Amino-3-(dialkylamino)propenenitriles were reacted with acetylenecarboxylates to give 2(1H)-pyridone derivatives. The reaction with ethyl propynate alforded dienamino ester intermediates which cyclized in sodium ethoxide/ethanol to 5-cyano-2(1H)-pyridone. The reaction with diethyl acetylenedicarboxylate gave directly the 2(1H)- pyridone derivatives

The reaction of N1-acetylacetamidrazones 1 with N-[bis(methylthio)methylene]cyanamide (2) at room temperature in the presence of potassium carbonate in dimethyl sulfoxide affords good yields of ethyl 4-acylhydrazino-2-amino-6-methylthio-5-pyrimidine carboxylate 3. By briefly refluxing compounds 3 in dimethyl sulfoxide, 1,2,4-triazolo[4,3-c]pyrimidine derivatives 4 were obtained. When equimolecular amounts of N1-acylacetamidrazones and compounds 2 were refluxed in dimethyl sulfoxide/toluene, compounds 4 were obtained directly.

Several new 1-acylamino-2-alkyl-4-arylimidazoles were synthesized. The compounds were obtained by reaction of N1-acylacetamidrazones and alpha-bromoketones. The antimicrobial activity of the prepared compounds was tested.

The reaction between 3-amino-3-(dialkylamino)propenenitriles 1 and sodium thiocyanate in presence of bromine, provides an efficient route for the synthesis of 2-amino-5-cyano-4-(dialkylamino)thiazoles 3

A convenient synthesis of 4-amino-7-(dialkylamino)pyrido[2,3-d]pyrimidines via cyclization of functionalized pyridines is reported. The preparation of the starting pyridines from 3-amino-3-(dialkylaraino)propene-nitriles and ethoxymethylenemalononitrile is described.

The reaction of N1-acyl-2-ethoxycarbonylacetamidrazones 1 with diethyl ethoxymethylenemalonate (EMME) is reported. By refluxing equimolecular amounts of 1 and EMME in DMSO/toluene (or ethanol) solution, the 1-acylamino-2(1H)-pyridones 2 were obtained in good yield. When the reaction was performed in ethanolic solution in the presence of triethylamine, the 6-acylhydrazino-2(1H)-pyridones 3 were obtained.

The 3,5-diaminoisothiazole derivatives 23-42 were synthesized in excellent yields by oxidative cyclization of 3-amino-3-(dialkylamino)propenethioamide derivatives. These intermediates and the isothiazole derivatives were tested in vitro for their antimicrobial activity.

The reaction of 1-acyl-3-amino-5-pyrazolones (1) with ethyl ethoxyme- thylenecyanoacetate and ethoxymethylenemalononitrile (2) is described. Thermal cyclization in phenyl ether of the obtained pyrazolacryloni- triles (3) provides good yields of pyrazolopyridin-3-ol derivatives (4)

Enaminonitriles 1 react in mild conditions with β-trifluoroacetylvinyl ethers 2 to give the pyridine derivatives 4. The reaction involves the formation of the intermediate 3, that can be isolated when enol ether 2a is used.

The heterocyclization of 3-aminopropenethioamides 1 and 2 with 2-bromoacetophenone is reported. The p-toluenesulphonic acid catalyzed reaction gives a direct route to 1,4-thiazepines 3 and 5, while in the presence of triethylamine thiophene 4 and 1,4-thiazepin-5-one 6 are obtained.

The reaction of propenethioamides 1 with bromoketones 2 and 3 led in acidic medium to the formation of 1,4-thiazepines 6 and 7. The pyrrole derivatives 4 and 5 were obtained by reaction of 1 with 2 and 3 in basic medium.

Polyfunctionalized trifluoromethylpyridines 4, 5 were readily synthesized from trifluoroacetylvinyl ether 3, using N1-acylacetamidrazones 1,2 as starting material.

The reaction between N1-acylacetamidrazones 1 and enol ether 2 is described. Depending on the reaction conditions and on the substitution pattern of amidrazones 2-acylhydrazino-4-methyl-6-trifluoro-methylpyridines 3 and/or 2-acylhydrazino-6-methyl-4-trifluoromethylpyridines 4 were obtained.

A simple approach to the fluorinated 1,5-benzoxazepine ring system is described. By reacting commercially accessible aminophenols 1 and the trifluoroacetylvinyl ether 2, high yields of enaminones 3 were obtained. Functionalization of methyl group of compounds 3 gave rise to dieneamines 4 that were cyclized in acidic environment to benzoxazepine derivatives 5.

Readily accessible fluorinated N-arylenaminones 3 were reacted with N,N-dimethylformamide dimethylacetal to produce functionalized hexadienones 4 . Ring closure of 4 with ammonium acetate afforded selectively N-aryl-2-(trifluoromethyl)-4-pyridinamines 5 in good to excellent yields.

Simple and convenient synthesis of hitherto unknown 3,5-diaminopyrazole-4-carbothioamides 3 as well as new ethyl 3,5-diaminopyrazole-4-carboxylates 7 is reported. The key intermediates were 2-cyano-propenethioamides 2 and 2-(ethoxycarbonyl)propenethioamides 5 which were readily obtained by reaction of phenyl isothiocyanate with 3-(2-acylhydrazino)-3-aminopropenenitriles 1 and ethyl 3-(2-acylhydrazino)-3-aminopropenoates 4 respectively. Intramolecular cyclization of compounds 2 afforded pyrazole-4-carbothioamides 3 while propenethioamides 5 gave pyrazole-4-carboxylates 7.

4-(2-Pyridinylamino)-1,1,1-trifluoro-3-penten-2-ones 3, obtained from the reaction of commercially available 2-aminopyridine derivatives and 4-methoxy-1,1,1-trifluoro-3-penten-2-one 2, were converted to 6-(dimethylamino)-4-(2-pyridinylamino)-3,5-hexadien-2-ones 4 by treatment with dimethylformamide dimethyl acetal. Azannulation of hexadienones 4 afforded 4-(2-pyridinylamino)-2-trifluoromethylpyridines 5 and 2-(trifluoroacetylmethylene)pyrido[1,2-a]pyrimidines 6, classes of compounds particularly interesting from a chemical and biological point of view.

A series of 6-thioxopyrimidines (5, 6), their 6-oxo- analogs (11-14), and pyrimidine-2,4-diones (20-26), were synthesized and evaluated for their antitumoral activity against 60 tumoral cell lines. The activity of propenethioamide (3, 4) and propeneamide (7-10 and 15-19) intermediates is also reported. Among the tested compounds the thioxopyrimidine 5c, bearing an N'-benzyl group, showed the best cytostatic activity. Furthermore, high selectivity and cytotoxic activity on the HOP-92 cell line of non-small cell lung cancer was exhibited by 3-amino-2-[(methylamino)thioxamethyl]-3-pyrrolidino-2-propenenitrile (3a).

A new series of S-alkylisothiosemicarbazones of 3- and 4-pyridincarboxaldehyde and 4-fluoro- and 4-trifluoromethylbenzaldehyde was synthesized and evaluated for biological activity against various Mycobacterium strains. Inhibitory activity against Mycobacterium tuberculosis H37Rv ATCC 27294 and INH-R ATCC 35822 was compared with activity against clinical isolated Mycobacteria as well as against MOTT. Some of newly prepared compounds showed best inhibitory values against clinical isolated Mycobacteria, besides to low citotoxicity values.

A series of new 1,4-diarylimidazol-2(3H)-one derivatives and their 2-thione analogues has been prepared and evaluated in vitro for antitumor activity against the NCI human cancer cell panel. Compounds bearing a 3,4,5-trimethoxyphenyl ring linked to either N-1 or C-4 position of the imidazole core demonstrated an interesting profile of cytotoxicity with preferential activity against leukemic cell lines. Compound 13 exhibited a potent antitumor activity against MOLT-4 (GI50 = 20 nM) and SR (GI50 = 32 nM) cell lines.

Hydrogen absorption and desorption properties in LaMg 2 Ni compound are presented. Nanostructured phases have been obtained by means of ball milling in order to study the influence of the microstructure on the absorption/desorption properties. The structural and hydriding properties were examined by X-ray diffraction, thermal analysis, hydrogen pressure–composition and thermal desorption measurements. Ball milling of as-cast compound gives a significant refinement of the microstructure. Hydrogenation at 443 K leads to the formation of LaMg 2 NiH 7 , but at higher temperatures (523 K) LaH 2 is produced. Two hours of ball milling promote the formation of LaH 2 under hydrogenation at 443 K. Thermal desorption up to 983 K of hydrogenated samples leads again to parent LaMg 2 Ni phase.

The regioselectivity of coupling phenyl isocyanate to 3-(2-acylhydrazino)-3-aminopropenenitriles and ethyl 3-(2-acylhydrazino)-3-aminopropenoates as simple access to aminopyrazole derivatives, endowed with potential antitumoral activity, is reported. 3-(2-Acylhydrazino)-3-aminopropenenitriles react with phenyl isocyanate to afford 3-amino-3-(2-acylhydrazino)-2-phenylaminocarbonyl-2-propenenitriles. These key intermediates were cyclized into 3,5-diaminopyrazole-4-carboxamide derivatives. Preliminary results of poor antiproliferative activities of these compounds are also reported.

The preparation of thiazole derivatives through reactions of ethyl 3-amino-3-acylhydrazinopropenoates (1) with inorganic thiocyanates and thiourea was investigated. The reaction of 1 with sodium thiocyanate, in acetic acid in the presence of bromine, afforded ethyl 3-acylamino-4-amino-2,3-dihydro-2-iminothiazole-5-carboxylates (3) selectively. On reacting the same compounds (1) with thiourea, in acetic acid and in the presence of bromine, 4-acylhydrazino-2-aminothiazole-5-carboxylates (4) were yielded. The structure of the representative compound (3c), ethyl 4-amino-3-benzoyl-amino-2,3-dihydro-2-iminothiazole-5-carboxylate has been solved by means of X-Ray crystallographic data analysis.

2,4-Diamino-6-methylthiopyrimidines 1 reacted with sodium methoxyde and benzylamine to give the corresponding 6-methoxypyrimidine and 6-benzylaminopyrimidine derivatives 2 and 4 respectively. The reaction of 1 with hydrazine hydrate, in ethanol, gave 6-hydrazino derivatives 6. However, by treating pyrimidines 1 in boiling hydrazine hydrate 3,6-diamino-4-hydrazino-1H-pyrazolo[3,4-d]pyrimidine 5 was obtained. The 6-hydrazinopyrimidines 6 could be converted into the pyrazolo[3,4-d], triazolo[4,3-c] and tetrazolo-[1,5-c]pyrimidines 7, 8 and 9 by the action of heating, trimethyl orthoformate and nitrous acid, respectively.