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The G protein-gated inwardly-rectifying potassium channels (GIRK, Kir3) are a family of inward-rectifying potassium channels, and there is significant evidence supporting the roles of GIRKs in a number of physiological processes and as potential targets for numerous indications. Previously reported urea containing molecules as GIRK1/2 preferring activators have had significant pharmacokinetic (PK) liabilities. Here we report a novel series of 1H-pyrazolo-5- yl-2-phenylacetamides in an effort to improve upon the PK properties. This series of compounds display nanomolar potency as GIRK1/2 activators with improved brain distribution (rodent Kp > 0.6).

A new protocol has been developed for the efficient synthesis of structurally diverse N-cyclohexyl-2-(2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,5]diazepin-3-yl)-2-phenylacetamides through a one-pot, five-component condensation reaction of an aromatic diamine, an aromatic aldehyde, an isocyanide, ethyl malonyl chloride, and water in dichloromethane with good yields, at ambient temperature, in the presence of MgCl2 as a catalyst.

An easy, efficient, and environmentally friendly method for the synthesis of N-(2-alkyl/aryl-4-phenyl-1H-imidazol-1-yl)-2-phenylacetamides from the reaction of phenyl acylbromides and phenylacetohydrazide derivatives has been presented. Shorter reaction times, simple workup procedure, no catalyst requirement, and use of small quantities of organic solvent are the most obvious advantages of this protocol.

New tetrahydro-1H-1,5-benzodiazepin-2-phenylacetamides were synthesized in good yields by a four-component reaction of benzylidene Meldrum's acid, benzene-1,2-diamines, isocyanides, and water in CH2Cl2 at room temperature.

Various N-substituted phenylacetamides were alkylated using different alkylating agents under neutral and basic conditions. Reactions were performed at different reaction temperatures and in various solvents. Also, a number of various catalysts were used including phase-transfer catalysts. Reactions were followed using GC or GC-MS technique and the presence as well as the yields of the alkylation products were established. Generally, the best yield and high selectivity in the studied reactions were achieved under basic conditions where in the certain cases some products, mostly N-product were obtained solely in quantitative yields.

Benzylation of N-(4-chlorophenyl)-2-phenylacetamidewith benzyl chloride in the presence of powdered potassium hydroxide under various reaction conditions was performed in order to establish the possible reaction products. Different temperatures and ratios of reactants and solvents were used. The reactions were also carried out in the presence of different phase-transfer catalysts in toluene as a solvent. The formation of the reaction products was followed using gas chromatography. On the basis of the obtained results, the reactivity and the orientation in the alkylation reaction of the investigated amide is discussed. N-(4-hlorfenil)-2-fenilacetamid je alkilovan benzil-hloridom u različitim rastvarač ima u prisustvu sprašenog kalijum-hidroksida na različitim temperaturama. Reakcije su izvođene u prisustvu različitih međufaznih katalizatora kao i bez katalizatora u cilju ispitivanja uticaja reakcionih uslova na reaktivnost i orijentaciju reakcije alkilovanja ispitivanog jedinjenja.

N-(4-Nitrophenyl)-2-phenylacetamide was alkylated with benzyl chloride in the presence of powdered potassium hydroxide at different temperatures and in various solvents in order to establish the reactivity and orientation in the reaction. The reactions were also carried out in the presence of different phase-transfer catalysts in toluene. Product formation was followed by GC. The obtained results were compared to the results of the benzylation of other N-substituted 2-phenylacetamides, especially of N-phenyl-2-phenylacetamide. N-(4-Nitrofenil)-2-fenilacetamid je alkilovan benzil-hloridom u različitim rastvarač ima u prisustvu sprašenog kalijum-hidroksida na različitim temperaturama. Reakcije su izvođene u prisustvu različitih međufaznih katalizatora kao i bez katalizatora u cilju ispitivanja uticaja reakcionih uslova na reaktivnost i orijentaciju reakcije alkilovanja ispitivanog jedinjenja.

Advantages of the new method are simple work-up procedure, no catalyst requirements, and use of small quantities of organic solvents.

We report a facile one-pot, three-step synthesis of N-(4-(2-aminopyridin-4-yl)thiazol-2-yl)-2-phenylacetamides via condensation of 2-p-methoxybenzylamino-4-acetylpyridine with phenylacetylthioureas.

Various N - t -butyl- N -substituted 2-phenylacetamides, PhCH 2 CON( t -Bu)R, wherein R is methyl, ethyl, n -propyl, n -butyl, i -propyl, phenyl and cyclohexyl, were synthesized. Depending on the kind of substituent on the nitrogen atom, some of the examined amides exist in different conformational forms. 1 H NMR and 13 C NMR spectra of these unsymmetrically N , N -disubstituted amides have been studied and peaks have been assigned in each case to the two possible conformational isomers, arising from the lack of free rotation about the C(O)N bond. The relative distribution of cis and trans isomers has been established by means of different coupling constants and the NOE difference technique. Information about fragmentation routes, and the effect of overall and partial structures were obtained by the study of the metastable ions. The results are in accordance with our previous investigations of the structures of N , N -disubstituted 2-phenylacetamides.

New tetrahydro-1H-1,5-benzodiazepin-2-phenylacetamides were synthesized in good yields by a four-component reaction of benzylidene Meldrum's acid, benzene-1,2-diamines, isocyanides, and water in CH2Cl2 at room temperature.

As a part of a study on the structural characteristics of some new various N-alkyl-N-substituted 2-phenylacetamides the infrared and 1 H N.M.R. spectra were obtained and interpreted. The synthesis of a various N-n-propyl-N-alkyl 2-phenylacetamides of the general formula PhCH 2 CON(nPr)R, wherein R is ethyl, isopropyl, n-butyl, t-butyl and cyclohexyl, were performed. The corresponding mixed secondary amines of the type HNnPrR were obtained by catalytic hydrogenation of the synthetized propylidenealkylamines. The 1 H N.M.R. spectra of these unsymmetrically N,N-disubstituted amides have been studied and the peaks have been assigned in each cases to two possible conformational isomers, arising from the lack of free rotation about the C(O)N bond. These results are in accordance with our previous investigation of the structure of N-substituted 2-phenylacetamides.

As a part of a study on the structural and vibrational properties of some new various N-alkyl-N-substituted 2-phenylacetamides, the infrared and 1H n.m.r. spectra were obtained and interpreted. The synthesis of a various N-methyl-N-substituted 2-phenylacetamides of the general formula PhCH2CON(CH3)R, in which the substituent group is (C3–C7) cycloalkyl group, were performed. The 1H n.m.r. spectra of these unsymmetrically N,N-disubstituted amides have been studied and the peaks have been assigned in each case to two possible conformational isomers, arising from the lack of free rotation about the C(O)N bond. These results are in accordance with our previous investigation of the structures of N-substituted 2-phenylacetamides.

In a continuation of our previous works the conformations of some new rigid N-bicyclo substituted 2-phenylacetamides, PhCH 2 CONHR, were investigated by vibrational, 1 H n.m.r. and mass spectra. N-monosubstituted 2-phenylacetamides were obtained by using the known Schotten-Baumann reaction of acylation of amines with phenylacetyl chloride. From spectroscopic data, the different conformational isomers were assigned and its structure undoubtly proven. On the other hand it can be concluded that the bulkiest substituent on the nitrogen atom have led only to the trans form.

The pyrolyses of cyanoacetamides, 2-phenylacetanilide, 2,2-diphenylacetanilide and 2,2,2-triphenylacetanilide have been studied. The pyrolysis of cyanoacetamides gave the corresponding isocyanates and acetonitrile. On the other hand, the pyrolysis of 2-phenylacetanilide and 2,2-diphenylacetanilide gave a small amount of phenyl isocyanate, along with various byproducts. The pyrolysis of 2,2,2-triphenyl-acetanilide, however, against expectation, did not give isocyanate; only a tarry product resulted.

The syntheses of a various N-methyl-N-substituted 2-phenylacetamides of the general formula PhCH2CON(CH3)R, wherein, R is ethyl, n-propyl, isopropyl and t-butyl group, were performed. The 1H n.m.r. spectra of these unsymetrically N,N-disubstituted amides have been studied and the peaks have been assigned in each case to the two possible conformational isomers, arising from the lack of free rotation about the C(O)N bond. Although the cis form predominates, the percentage of cis isomer increases as the other nitrogen substituent becomes more bulky. These results are in accordance with our previous investigation of the structures of N-monosubstituted 2-phenylacetamides.