alpha-(1H-imidazol-1-ylmethylene)ketones with antimycotic activity

A series of title compounds were synthesized starting from heterocyclic alpha-hydroxymethyleneketones and 1,1'-carbonyldiimidazole and tested against gram-positive and gram-negative bacteria, as well as fungi. 7,8-Dihydro-6-(1H-imidazol-1-ylmethylene)-2-phenylquinazolin -5(6H)-one showed a remarkable activity against Candida krusei.     

Physiological activity of polymethylene and polyoxyethylene bis-(2-amino-1,3-diazepiniuim) iodides

A study was made of physiological activity of a series of new bisquaternary compounds in which the role of cation heads is played by the residues of 2-amino-1,3-diazepinium. Studies performed on a frog neuromuscular preparation showed that the compounds under test effectively block the responses of the postsynaptic membrane to acetylchinoline. The derivatives of diazepinium have pronounced hypotensive and ganglion-blocking properties. Octamethylene-bis-(2-amino-1,3-diazepinium) iodide that appeared to be the most effective of the compounds under test compares very favourably with benzohexonium. It was found to be 1.5 times more powerful as regards the ganglion-blocking and hypotensive activity.     

Aminomethyl derivatives of (benzisothiazolin-3-one-2-yl)acetic acid amides and 2-(1,2-benzisothiazoline-3-one-2-yl)propionic acid amides]

In the search for pharmacological active new derivatives of 1,2-benzisothiazolin-3-on amides of (3-oxo-1,2-benzisothiazolin-2-yl)acetic acid and 3-(3-oxo-1,2-benzisothiazolin-2-yl)propionic acid were obtained. In the reaction of these amides with formaldehyde and various second aryl amines the title compounds are formed. Morpholinmethylamide of (3-oxo-1,2-benzisothiazolin-2-yl)acetic acid showed activity against Trichomonas vaginalis. In the reaction of ethyl esters of (3-oxo-1,2-benzisothiazolin-2-yl) acetic- and -propionic acids with hydrazine hydrate products of ring-opening of isothiazole-2,2'-dithio-bis [N- (ethoxycarbonylmethyl)benzamide] and 2,2'-dithio-bis[N-(ethoxycarbonylethyl)benzamide are formed.     

Aryl esters of N-benzyldithiocarbamic acid with antimycotic activity

Some aryl esters of N-benzyldithiocarbamic acid [substances (I leads to XVI)], in which S aryl substituents were hydrophylic or potentially hydrophylic groups, were tested for in vitro antifungal activity against the following strains: Candida albicans, Saccharomyces cerevisiae and Trichophyton mentagrophytes. The substances were prepared by condensation of benzylisothiocyanate with suitable benzenethiols. The results, given in Table I, show the marked activity as antifungal agents of the N-benzyldithiocarbamic acid aryl esters studied; the antifungal activity, connected with the N-benzyldithiocarbamic group, is only slightly influenced by the nature of the substituents.     

Synthesis and antimycotic activity of some 3-(1-imidazolylmethyl)indoles

The title compounds were synthesized and tested for their in vitro antimycotic activity. 1-Ethyl-3-{[2,4-dichloro-α-(1-imidazolyl)]phenethyl}indole ( 5 ) exhibited appreciable activity against Cr. neoformans (MIC = 12,5μg/ml).     

Antifibrinolytic and antimycotic properties of 2-thiontetrahydro-1,3,5-thiadiazine]

A series of tetrahydro-1,3,5-thiadiazine-2-thiones have been tested for their fungistatic and antifibrinolytic effects. The fungistatic activity depends upon the substitution of nitrogen in positions 3 and 5 of the ring system. But it is, however, only the derivatives that are able to split off the antifibrinolytically active w-amino acids by solvolysis which produces antifibrinolytic effect in vivo.     

Drug-induced porphyrin biosynthesis--XIII. Role of lipophilicity in determining porphyrin-inducing activity of aliphatic amides after blockade of their hydrolysis by bis-(rho-nitrophenyl)phosphate.

Hexanamide and heptanamide were the best substrates for a chick embryo liver amidase, and activity decreased with shorter or longer chain lengths. Amides branched at the 2-carbon atom were poor substrates and those branched at the 2- and 3-carbon atom were not hydrolyzed. Hydrolysis of both straight- and branched-chain amides was inhibited to varying extents by bis-[p-nitrophenyl]phoshate (BNPP). Branched-chain amides, while poor substrates of the amidase, were hydrolyzed solely by a BNPP-sensitive enzyme, while the straight-chain amides were hydrolyzed by a BNPP-sensitive and a BNPP-resistant enzyme.The porphyrin-inducing activity of a series of aliphatic amides was studied in a chick embryo liver cell culture system in the presence and absence of BNPP. The potency of sterically hindered branched-chain aliphatic amides was found to be the same in the presence and absence of BNPP and could be correlated with lipophilicity. However, sterically unhindered aliphatic amides which were moderately potent in the absence of BNPP exhibited an increase in potency in the presence of BNPP. The potency of the straight-chain aliphatic amides after BNPP pretreatment could be correlated with lipophilicity. It was concluded that porphyrin-inducing activity of aliphatic amides in chick embryo liver cell culture depends upon lipophilicity and resistance to rapid metabolism to compounds of lower lipophilicity.     

Derivatives of phenoxyacetamide and antimycotic activity

Novel N-(3-methyl-4-R-isoxazol-5-yl)-2-R1-4-R2-phenoxyacetamides and N-(3-methyl-4-R-isoxazol-5-yl)-2-(2-R1-4-R2-phenoxyacetamido) benzamides were prepared and tested against Candida albicans and Cryptococcus neoformans. The results of the antimicrobial assay showed that the presence of two amidic groups usually enhances antimycotic activity.     

Spectrophotometric assay of 5,5'-(salicylidene)bis-(2-thiobarbituric acid)

The spectrophotometric assay of 5,5′-(salicylidene)bis-(2-thiobarbituric acid), which shows interesting pharmacological perspectives, is proposed, applying the conventional and differential photometries. The conventional photometry is developed at pH 4.00 (NaOAc-HOAc buffer). The differential photometry is realized for two series of pH (pH 10.5/13.5 and pH 2.0/10.5). A comparative study between the different photometries indicates a higher precision for the differential photometry in the event of pH 2.0/10.5.     

Synthesis of some new biologically active bis-(thiadiazolotriazines) and bis-(thiadiazolotriazinyl) alkanes

4-Amino-3-mercapto-1,2,4-triazin-5(4H)-ones (1) were condensed with dicarboxylic acids 2 to yield bis-(4-oxo-4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-7-yl)alkanes (3b-d,f-h,j-l,n-p) and bis-thiadiazolotriazines (3a,e,i,m). All the newly synthesised compounds were characterised by analytical, IR, NMR and mass spectral studies. Some of the newly synthesised compounds were screened for their antibacterial and antifungal properties. Among the tested compounds, compound 7,7'-(1,4-butanediyl)-his-(3-t-butyl-4-oxo-4H-1,3,4-thia-diazolo[2,3-c]-1,2,4-triazine (3p) exhibited highest degree of antifungal activity.     

Synthesis and potential antimycotic activity of 4-substituted-3-(thiophene-2-yl-methyl)-Delta2-1,2,4-triazoline-5-thiones

In the reaction of hydrazide of thiophene-2-acetic acid (1) with isothiocyanates, the respective thiosemicarbazides 2a-g were obtained. Further cyclization with 2% NaOH led to formation of 4-substituted-3-(thiophene- 2-yl-methyl)-Delta2-1,2,4-triazoline-5-thiones (3a-g). These compounds showed promising antimycotic activity.     

Stereoselective LSD-like activity in d-lysergic acid amides of (R)- and (S)-2-aminobutane.

The (R)- and (S)-2-butylamides of d-lysergic acid were prepared and evaluated in behavioral and biochemical assays of 5-HT2 agonist activity. In rats trained to discriminate 0.08 mg/kg LSD tartrate from saline, both isomers completely substituted for the training stimulus. Similarly, both isomers were found to possess very high affinity in displacing [125I]-(R)-DOI ([125I]-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane) from rat cortical homogenate 5-HT2 receptors and in displacing [3H]-8-OH-DPAT ([3H]-8-hydroxy-2-(di-n-propylamino)tetralin) from rat hippocampal 5-HT1A receptors. The difference in activity between the two isomeric amides was significant in both the behavioral and binding assays, with the R isomer possessing greater potency. Molecular mechanics were used to predict the active geometries of the subject compounds. It was found that the (R)-2-butylamide has a conformation quite similar to LSD, while the (S)-2-butylamide does not. These results suggest that stereochemical properties of the amide substituent of hallucinogenic lysergamides may exert a critical influence on activity. It is concluded that the conformation of the amide function may directly affect binding through stereoselective interactions with a hydrophobic region on the receptor, indirectly by inducing conformational changes elsewhere in the molecule, or by a combination of these two mechanisms.