Pharmacological properties of esters of 1-alkyl-2-hydroxyalkylpyrrolidine and their quaternary derivatives

A series of esters of 1-alkyl-2-hydroxyalkylpyrrolidine and their quaternary derivatives have been shown to possess significant anti-acetylcholine activity. The benzilic acid esters were the most active, followed by xanthene-9-carboxylic acid, fluorene-9-carboxylic acid and diphenylacetic acid esters in that order. The quaternary derivatives were more active than their corresponding tertiary compounds both in vivo and in vitro. The most active compound of the series tested in vivo was (1-methylpyrrolid-2-yl)methyl benzilate methiodide and was as potent as atropine. There was a progressive decrease in anti-acetylcholine activity and a proportional increase in local anaesthetic activity as the number of carbon atoms was increased from 1 to 3 in the pyrrolidyl side-chain of the tertiary salts of the benzilic acid ester series. Likewise increasing the size of the group on the nitrogen atom led to a decrease in anti-acetylcholine activity and an increase in local anaesthetic activity. Quaternization of the tertiary salts resulted in a loss of local anaesthetic activity. Most of the compounds tested possessed some antihistamine properties, while papaverine-like activity was confined to the tertiary salts only. No significant neuromuscular blocking activity was evident.     

Synthesis of 1-alkyl-3,4-dihydroisoquinoline derivatives and study of their effect on arterial pressure

A series of 1-alkyl-3,4-dihydroisoquinolines and the related 4-alkyl-1,2-dihydro-benzo[f]isoquinolines was synthesized using reactions of dialkylbenzylcarbinols and their naphthyl analogs with alkylcyanides. Experiments showed that 1-alkyl-6,7-dimethoxy-3,4-dihydroisoquinolines typically produce a hypotensive action, while the benzo-annelated structures usually exhibit a hypertensive effects. The most active compound decreases the arterial pressure in cats by 52 Torr and the effect lasts for about 4 hours. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 3, pp. 15–17, March, 2006.     

Synthesis and antimicrobial activity of some new 1-alkyl-2-alkylthio-1,2,4-triazolobenzimidazole derivatives

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo-[2,3-a]benzimidazole-2-thione intermediate was reacted with one equivalent of alkyl halides to give the corresponding 2-alkylthio derivatives, which were further alkylated through the reaction with another one equivalent of different alkyl halides to afford the target compounds; 1-alkyl-2-alkylthio-1,2,4-traizolo[2,3-a]benzimidazoles. On the other hand, the 1,2-disubstituted derivatives with two identical alkyl substituents were prepared by the reaction of 1,2,4-triazolo[2,3-a]benzimidazole-2-thione with two equivalents of the alkyl halides. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their antibacterial and antifungal activities. Most of the tested compounds proved comparable results with those of ampicillin and fluconazole reference drugs. The study indicated that, the antibacterial as well as the antifungal activities of the test compounds were improved with increase in the bulkiness of the introduced alkyl groups. Also, some active antibacterial compounds were tested for their antimycobacterial activity. All the test compounds showed equipotent antitubercular activity as that of INH as a reference drug.     

Pharmacodynamics of acidic triamterene derivatives and their esters and amides

The diuretic, natriuretic and antikaliuretic effects of two acidic triamterene derivatives, carboxymethoxytriamterene (C2) and carboxybutoxytriamterene (C5), as well as some of their esters and amides were studied in male Wistar rats. The acids and their esters possess similar natriuretic and potassium retaining properties. The esters are nearly completely hydrolyzed to the corresponding acids; therefore, the acids themselves represent the active principle. Compared to the acids and esters the amides have a stronger effect on natriuresis and antikaliuresis. As the amides are excreted partially unhydrolyzed in urine, their pronounced natriuretic and potassium retaining effect must be due to the intact molecule.     

Synthesis of some 2-benzoxazolinone derivatives and their analgesic properties

In this study, eight new 1-(2-benzoxazolinone-6-yl)-2-(4-arylpiperazine-1-yl)ethanol and -propanol derivatives have been prepared. Their structures have been elucidated by IR- and 1H-NMR-spectra and by elementary analysis. The analgesic activities of these compounds, using modified Koster's test have been investigated. 1-(5-Chloro-3-methyl-2-benzoxazolone-6-yl)-2-[4-(2-methoxyphenyl)p iperazine-1- yl]ethanol has been found more active than O-acetyl-salicylic acid, respectively.