I. S. Nikolaeva

Synthesis and biological activity of 5-oxy-6-bromoindole substitutes

Aminoalkyl derivatives of 5-oxyindole represent considerable interest in the search for biologically active compounds [3-71. Thus, for example, the 2-aminoalkyl, 2,4-bis, and 4,6bis(alkylamino)methyl derivatives of 5-oxyindole exhibit pharmacological and antiviral activity [5-7]. Antiserotonin activity equivalent to the activity of l-benzyi-2-methyl-5methoxytryptamine (BAS) has been found in the 4-dialkylaminomethyl derivatives of 5-oxyindole [3], and antitubercular activity has been found in a number of dialkylaminoethyl derivatives of 5-oxyindole [4].

A new antiviral preparation oxolene

A chemica l study of oxolene with influenza showed that its local use on the mucous membrane of the nose and throa t has a therapeut ic effect and r e m o v e s the ca t a r rha l effects f r o m the side of the upper r e s p i r a to ry t r ac t [2]. In add i t ion theprophylac t i c e f fec t iveness of oxolene with r e spec t to influenza was e s t a b l ished in a broad epidemiologica l expe r imen t and during a study on vo lun teers . The coefficient of e f f ec t iveness of oxolene is equal to 40%, while the known ant iv i ra l p repara t ion amantadin used abroad has a coefficient of e f fec t iveness of 25% [3]. In 1969 oxolene was approved by the Pha rmaco log ica l Commit tee of the Depar tment of Public Health of the USSR as a medium of individual prophylaxis and curing of influenza upon local applicat ion. A cl inical study of the therapeut ic effect of oxolene in ophthalmological and d e r m a tological medica l inst i tut ions es tab l i shed its e f fec t iveness in curing v i r a l d i seases of the eye: adenovi rus induced kera toconjunet iv i t i s and herpet ic kera t i t i s [4, 5], and v i r a l sMn d i seases , i .e., he rpes s implex, v e s i cu la r herpes , shingles, mo l luscum eontagiosum, and Duhring s d i sease . In addition, the favorab le effect of oxolene on the cour se of p s o r i a s i s was made apparent . Oxolene was approved by the Pha rmaco log ica l Commit tee of the Depar tmen t of Publ ic Health of the USSR for local use in the t r e a t m e n t of these d i s e a s e s .

Synthesis and testing of antiviral activity of azaheterocycles with hydroxyl-containing fragments as substituents

Among acyclic nucleosides and their analogs are found the effective pharmaceutical compounds acyclovir and gancyclovir, as well as other compounds having high antiviral activity [5]. The antiviral activity of this type of compound is apparently due to the presence in its structure of hydroxyl groups with the potential to undergo phosphorylation in vivo. It is believed that this phosphorylation occurs to a greater degree in virus-infected than in uninfected cells. The triphosphates thus formed serve as active and selective inhibitors of viral-coded DNA polymerase, and are responsible for the antiviral activity of these compounds [6, 7]. From this point of view, it was of interest to study the antiviral activity of heterocyctic compounds not containing purine fragments, but having substituents with one or more alcoholic hydroxyl groups, which in principle could be phosphorylated in vivo. As objects of this type for study, in the present work we chose derivatives of 2-aminomethylene-4,5dehydropyrroldone-3 (Ia-c), 2-aminomethyleneindolinone3 (IIa-c), pyrrolo [ 1,2-a]indole (IIIa-c), andpyrido[3,2:4, 5 ]thieno[3,2d]pyrimidine (IVa-d). Synthesis of the above compounds was carried out via previously described enamines [2, 3], by their transamination, or by reaction of tricyclic chloroderivative V with different amines:

6-Toluoyl-1,2-naphthoquinones—synthesis, reactions, and antiviral activity

We have already shown that different substituted 1,2-naphthoquinones, including 6-halo1,2-naphthoquinones, exhibit an antiviral activity in experiments [i, 2]. These investigations led to the production of an original antiviral agent with a systemic action, i.e., 6-bromo-l,2,-naphthoquinone [3-6]. It is therefore interesting to study the antiviral activity of 1,2-naphthoquinones with other substituents in the 6-position.

Synthesis and antiviral activity of 6-halo-1,2-naphthoquinones

In connection with the high antiviral activity of 6-bromo-l,2-naphthoquinone (bonaphrhone) [1-4], it was of interest to study the nature of the effect of the halogen substituent in the 6 position of 1,2-naphthoquinone on the direction and character of its antiviral activity. In the present work we have synthesized and studied the action of 6-fluoro-, 6chloro-, and 6-iodo-l,2-naphthoquinones on the influenza viruses A/PR/8/34 (HONI), A/England 42/72 (H3N2), and simple herpes virus of type I, strain I-C. Thereupon the activity of the latter was compared with the antiviral activity of bonaphthone.

Bonaphton — A New Antiviral Chemotherapeutic Drug

Orthonaphthoquinone and many of its derivatives exert antiviral activity. Conditional estimation of antiviral action of compounds studied is represented in Table 1.