Pharmacological effects of triazolo[4,3-d] and tetrazolo[1,5-a][1,4]benzodiazepines on the central nervous system.

A series of tricyclic 1,4-benzodiazepines, fundamentally 5H-s-triazolo[4,3-d] and tetrazolo[1,5-a][1,4]benzodiazepines, were tested for acute toxicity and central nervous system effects in mice. All of these compounds, but especially 3, 4 and 5, showed a clear central depressant activity. Compounds 3, 4 and 5 also showed a moderate activity in antagonizing the deleterious effects produced by cardiazol but were ineffective in counteracting those elicited by strychnine. These same compounds 3, 4 and 5 presented a remarkable benzodiazepine-like action with a pharmacological profile similar to that of chlordiazepoxide.

Synthesis and preliminary pharmacological evaluation of thiophene analogues of viloxazine as potential antidepressant drugs.

A series of eight thienyloxymethylmorpholines, thiophene analogues of viloxazine, have been synthesized by three different routes. The preliminary pharmacological evaluation of this series shows antidepressant properties on the mice models used with a light sedative action. The structure-activity relationship is established in a first approximation.

Nonsteroidal anti-inflammatory activity of 1,2,4-triazolyl-heterocarboxylic derivatives.

A series of 1,2,4-triazolyl-thiophene and 1,2,4-triazolyl-pyrazole carboxylic acid derivatives was tested for acute toxicity and nonsteroidal anti-inflammatory activity. Some of these compounds showed potent analgesic activity and interesting nonsteroidal anti-inflammatory properties in different acute and chronic inflammation models.

Study of the antidepressant activity of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

A series of 23 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives were tested for acute toxicity and antidepressant activity in mice. Eight of the 23 compounds tested clearly antagonised the tetrabenazine effects and four of them (5, 7, 19, 23) showed activity values ranging from 40 to 75%, close to those shown by imipramine and viloxazine, the drugs chosen as reference standards. Compounds 7, 19 and 23 were also notably effective in the Porsolt test, shortening the immobility period of mice by more than 20%. The values obtained were very close to those elicited by imipramine and viloxazine. The most effective compounds in these tests were found among those bearing a primary amine or a benzoylamino group at the position 3 of the thieno[2,3-d]pyrimidine general structure (7, 19 and 23). The substitution of the thioxocarbonyl group at position 2 by a methylmercapto substituent maintained the activity (23). Compounds 7, 19 and 23 were chosen as prototypes for the design of new molecules with better antidepressant activity. These compounds did not present the adverse anticholinergic effects found in most tricyclic antidepressant drugs.

CNS effects of a series of 1,2,4-triazolyl heterocarboxylic derivatives.

A series of 1,2,4-triazolyl heterocarboxylic derivatives were tested for acute toxicity and CNS effects in mice. Several of these compounds demonstrated clear psychostimulant effects. Other components of the series, however, showed a definite central depressant activity. Some of the screened derivatives showed interesting anxiolytic properties.

Antidepressant activity of new hetero[2,1]benzothiazepine derivatives.

A number of thieno and pyrazolo[2,1]benzothiazepine derivatives as well as several synthetic intermediate compounds were tested for acute toxicity and antidepressant activity in mice. Some of these compounds were effective in the tetrabenazine and Porsolt tests.

Synthesis and antidepressant evaluation of new hetero[2,1]benzothiazepine derivatives.

As a part of a research program directed to the discovery of novel antidepressant agents, a series of new hetero[2,1]benzothiazepine derivatives was synthesized. Some of these compounds antagonized the ptosis and motor depression induced by tetrabenazine and were also active in the Porsolt forced swimming test.

Synthesis and anti-inflammatory evaluation of new sulfamoylheterocarboxylic derivatives.

A series of new sulfamoylthiophene and sulfamoylpyrazole carboxylic acid derivatives was synthesized. Some of these compounds show interesting analgesic properties and significant nonsteroidal anti-inflammatory activities in several models of inflammation.

Synthesis and antiplatelet activity of 1-tert-butylamino-3-(3-thienyloxy)-2-propanols.

The synthesis of new 1-tert-butylamino-3-(3-thienyloxy)-2-propanols by two alternative methods is described. Their initial antiplatelet activity evaluation against ADP, adrenaline, and collagen is reported, and the preliminary structure-activity relationships are established. The appropriateness of further pharmacological investigations, especially for the best compound of the series 1f, is indicated.

Anticonvulsant activity of aryl and hetarylsulfonylhydrazones.

A series of aryl and hetarylsulfonylhydrazones of aromatic aldehydes were tested for acute toxicity and anticonvulsant activity in mice. Some of these compounds were effective in the MES, pentetrazol and strychnine tests. Thiophene derivatives were the most active terms of the series.

Effects of Visnea mocanera extracts on the bleeding time, gastrointestinal transit and diuresis in rodents.

The present study examined the effect of several extracts of Visnea mocanera L. on the bleeding time and gastrointestinal transit in mice using the Duke test and charcoal meal method, respectively; they were also investigated in order to examine their renal effects. Results showed that V. mocanera extracts significantly inhibited both the bleeding time and gastrointestinal transit in mice. No diuretic activity of these extracts were detected. In contrast, they significantly reduced the urine volume. The study provides experimental support to the therapeutic advocation of V. mocanera in ethnomedicine for the treatment of diarrhoea and the healing of wounds.

Synthesis and pharmacological study of 5,6,8,9-tetrahydro-4H, 7H-pyrrolo[1,2-a]cyclopenta[b]thieno[3,2-f][1,4]diazepines.

The paper reports the synthesis of a series of 5,6,8,9-tetrahydro-4H, 7H-pyrrolo[1,2-a]cyclopenta[b]thieno-[3,2-f][1,4]diazepines and the results of the study on their CNS activity in mice. The pharmacological properties of a previously prepared series of 5,6,7,8,9,10-hexahydro-benzo-analogs is also described.

NSAI activity study of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

A series of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives endowed with anti-inflammatory and related pharmacological properties were submitted to a more extensive study to know their exact pharmacological profile and their possible side effects. The studied compounds possess a remarkable analgesic activity, devoid of central effects. They also show an interesting anti-inflammatory profile evidenced by their effectiveness in different experimental models of inflammation. In addition, these compounds exhibit none or very little activity on CNS, scarce toxicity and low gastrointestinal aggressivity.

4H-pyrrolo[1,2-a]thieno[3,2-f] and 4H-pyrrolo[1,2-a]thieno-[2,3-f][1,4]diazepines: synthesis and pharmacological evaluation.

As an extension of a previous work, in which a number of 4H-pyrrolo-[1,2-a]thieno[2,3-f][1,4]diazepines were described, a new series of derivatives of the isomeric pyrrolo[1,2-a]thieno[3,2-f]diazepines ring system has been synthesized. The products obtained, together with those reported in the previous paper, were tested for acute toxicity and CNS activity in mice.

Synthesis and anticonvulsant activity of new dibenzo[1,2]thiazepine S,S-dioxides.

A new series of 11-substituted 6,11-dihydro-6-methyl-dibenzo[c,f]-[1,2]thiazepine S,S-dioxides was synthesized. Some of the components show significant anticonvulsant activity in the MES, pentetrazol and strychnine tests. The more active compounds are devoid of neurotoxic effects.

Antimicrobial activity of Visnea mocanera leaf extracts.

A chemical study of Visnea mocanera leaves was carried out giving lupeol and beta-sitosterol fatty esters, as well as beta-sitosterol and the triterpenic betulinic, ursolic, platanic and 2 alpha,3 beta-dihydroxy-ursan-12-en-28-oic and 2 alpha,3 beta-dihydroxy-olean-12-en-28-oic acids. Studies of the antimicrobial activity of acetone and methanol extracts as well as an aqueous infusion were also performed and the good experimental results obtained justify the folk use of this species as a cicatrizant and vulnerary agent.

Neuroleptic activity of 10-(4-methyl-1-piperazinyl)-thieno[3,2-b] [1,5]benzoxazepine and benzothiazepine derivatives.

Two series of compounds, structurally related to clozapine (CAS 5786-21-0), were tested for their neuroleptic activity. The derivatives 7-chloro-10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzoxazepine and 7-chloro-10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzothiazepine at high doses were not cataleptogenic and only very weakly antagonized the amphetamine-or apomorphine-induced stereotyped behaviour in the rat, whereas at low doses they antagonized the amphetamine-induced hypermotility in mice. Thus these compounds might be efficient neuroleptics with little propensity to cause extrapyramidal side effects. On the other hand, the unsubstituted compound 10-(4-methyl-1-piperazinyl)-thieno[3,2-b][1,5]benzothiazepine appeared to be an efficient neuroleptic agent with a greater propensity to cause these side effects.

Essential oils and antimicrobial activity of two varieties of Cedronella canariensis (L.) W. et B.

The qualitative and quantitative determination of the essential oils of the aerial part of two varieties of Cedronella canariensis (L.) W. et B., namely, C. canariensis var. canariensis and C. canariensis var. anisata have been performed, together with the study of the antimicrobial activity of both oils. The noteworthy inhibition exhibited against Bordetella bronchiseptica and Cryptococcus albidus may justify the popular use of the these plants in the treatment of certain diseases of the respiratory tract.

Synthesis and preliminary pharmacological study of thiophene analogues of the antipyretic and analgesic agent ethenzamide.

A preliminary pharmacological study of a thiophene analogue 1b of the analgesic and antipyretic agent Ethenzamide and of a closely related compound 1a showed that a great similarity exists among Ethenzamide and the thiophenic compounds for analgesic, antipyretic, ulcerogenic, hypothermic, and sedative effects. However, the acute toxicity in mice for the thiophenic compounds is notably higher than that of Ethenzamide.