Synthesis and antiviral properties of novel analogues of monophosphate and diphosphate bioactive forms of acyclovir.

New analogues (compounds 6, 7 and 9) of the mono- (8) and diphosphate (10) bioactive forms of the antiherpes drug acyclovir are described. In compound 6, the monophosphate moiety of 8 was replaced by an aminosulfonyloxy group, while in compounds 7 and 9, a phosphonoacetamidoxy and an O-ethyl phosphonoacetamidoxy moiety are, respectively present instead of the diphosphate one of 10. None of the compounds synthesized proved to possess an appreciable activity on herpes simplex virus (HSV) or human immunodeficiency virus (HIV).

Xanthine oxidase (XO). 4(5)-aminosubstituted-5(4)-carboxyamido-1H-1,2, 3-triazoles: a new class of monocyclic triazole inhibitors.

The 4(5)-aminosubstituted-5(4)-carboxyamido-1H-1,2,3-triazoles constitute a new class of monocyclic compounds as effective inhibitors of XO. In the past to these compounds the structure of 9-unsubstituted-8-azahypoxanthines was wrongly attributed. However some 8-azahypoxanthines obtained via a new annulation reaction have been described in this paper. The inhibitory activity of the title triazoles resulted greater than that shown by the corresponding 8-azahypoxanthines. The inhibitory competitive activity of 4(5)-n-pentyloxyoxalylamino-5(4)-carbamoyl-1H-1,2,3-triazole toward the oxidation of 8-n-pentylhypoxanthine disclosed that only one lipophilic pocket is present within the enzyme.

Xanthine oxidase (XO): relative configuration of complexes formed by the enzyme, 2- or 8-n-alkyl-hypoxanthines and 2-n-alkyl-8-azahypoxanthines. XII.

Several 2- or 8-n-alkyl-hypoxanthines and a 2,8-di-n-pentyl-hypoxanthine were synthesized and tested as substrates or inhibitors of Xanthine Oxidase (XO). 8-Alkyl derivatives showed a substrate behaviour, whereas 2-alkyl substituted compounds were non-substrates and inhibitors. 2,8-di-n-pentyl-hypoxanthine was ineffective as inhibitor. The comparison between their activity allowed us to conclude that the complexes formed by the enzyme and the cited n-alkylhypoxanthines or 2-n-alkyl-8-azahypoxanthines involve their N(3) and N(9) positions in all the cases. The position of the n-alkyl chain determines the disposition of the molecule inside the complex: 2-n-alkyl-hypoxanthines and 2-n-alkyl-8-azahypoxanthines gave complexes with the same orientation of heterocyclic moieties, opposite that given by 8-n-alkyl-hypoxanthines.

Synthesis and local anesthetic activity of some n-beta-diethylaminoethylnaphthalimides.

Some N-beta-diethylaminoethylnaphthalimides substituted in the 3 or 3 and 4 positions with alkoxy or butylamino groups or with alkoxy and amino groups (III) have been synthesized by reaction of the appropriate naphthalic anhydride with N,N-diethylethylenediamine. Some compounds (III) were tested to evaluate their anesthetic activity: compounds (III e) and (III f) have been shown to have a greater activity than lidocaine.

Synthesis of some substituted pyrido[1,2-a][1,8]naphthyridines.

Synthesis of a pyrido[1,2-a][1,8]naphthyridine (VII) was achieved starting from 7-amino-2,4-dimethyl-1,8-naphthyridine and diethyl ethoxymethylenemalonate. Some derivatives were subjected to pharmacological screening.

[1,2,3-triazole derivatives of arylalkanoic acids]. / Derivati 1,2,3-triazolici di acidi arilalcanoici.

A series of several 1,2,3-triazole derivatives, by reaction of p-azidophenylacetic and 2-(p-azidophenyl)propionic acids with active methylene compounds, was synthesized. Some of the derivatives obtained were subjected to pharmacological study and among these compounds (II m) showed an analgesic activity 2.5 times greater than phenylbutazone.

[Synthesis and pharmacological activity of 1,2,3-triazole derivatives of naphthalene, quinoline and pyridine]. / Sintesi ed esame farmacologico di derivati 1,2,3-triazolici della naftalina, chinolina e piridina.

The preparation of three series of 1,2,3-triazol derivatives, with a naphthalene, quinoline or pyridine ring in 1 position, is described. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.

[Synthesis and biological activity of 1,2,3-triazol-1,8-naphthyridines]. / Sintesi e attivita biologica di derivati 1,2,3-triazol-1,8-naftiridinici

The reaction of 2-methyl-5-azido-1,8-naphthyridine with active methylene compounds was investigated. Several naphthyridines which possess the 1,2,3-triazole ring as a substituent were obtained. Among these compounds (IV o) showed an analgesic activity twice that of phenylbutazone.

[Preparation of some pyrido (2,3-e)-1,4-diazepines]. / Preparazione di alcune pirido (2,3-e)-1,4-diazepine

By treating pyrido (2,3-e)-1,4-diazepinones with alkyl halides, N4-alkylpyrido (2,3-e)-1,4-diazepines were obtained. In addition a number of N1-alkylpyrido (2,3-e)-1,4-diazepines were prepared from alkyltetrahydronaphthyridinones by the Schmidt reaction. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.

1,8-naphthyridine derivatives: synthesis and pharmacological evaluation of beta-receptor blocking activity.

The synthesis of a number of 1-alkyl-7-(2-hydroxy-3-alkylaminopropoxy)-1,8-naphthyridin-2-ones is described. The compounds studied were prepared by reaction of 1-alkyl-7-hydroxy-1,8-naphthyridin-2-ones with epichlorohydrin. The substituted epoxy intermediates obtained were allowed to react with amines and gave the desired products. All the compunds prepared were devoid of beta-blocking activity.

[Reaction of 1,8-naphthyridine azides with ethyl acrylate]. / Reazione di azidi 1,8-naftiridiniche con acrilato di etile

The reaction of 1,8-naphthyridine azides with ethyl acrylate leads to the formation of 2-pyrazolines instead of 1,2,3-triazolines. Some of the compounds obtained have undergone pharmacological and microbiological (antibacterial) testing.

[Synthesis and biological activity of pyrido(2,3-e)-1,4-diazepine and of pyrido(2,3-b)(1,4)diazepine]. / Sintesi ed attivita biologica di pirido[2,3-e]-1,4-diazepine e di pirido[2,3-b][1,4]diazepine

The Schmidt reaction on tetrahydro-1,8-naphthyridin-4-ones gave pyrido [2,3-e]-1,4-diazepines and pyrido[2,3-b][1,4]diazepines. The preliminary pharmacological screening of some of these compounds showed no appreciable activity.

[Preparation and pharmacological study of some N-substituted amino-1,8-naphthyridines]. / Preparazione e indagine farmacologica di alcune alcune ammino-1,8-naftiridine n-sostituite

The synthesis of N-substituted amino-1,8-naphthyridines is described. Some products were subyected to pharmacological screening and the resulting data are reported.