Novel thiazolinyl, thiazolidinonyl, thiadiazolyl and oxadiazolyl-benzotriazole derivatives with potential antiinflammatory activity and minimum ulcerogenic effect.

Four novel series of 1H-benzotriazole derivatives; containing thiazolin, thiazolidin, thiadiazole and oxadiazole moieties; namely 1-[(3,4-disubstituted thiazolin-2-ylidene)hydrazinocarbonyl]methyl-1H-benzotriazoles 3a-1; 1-[3-substituted 5-ethoxycarbonyl-4-methyl thiazolin-2-ylidene)hydrazinocarbonyl]methyl-1H-benzotriazoles 4a-c; 1-[(3-substituted-4-oxothiazolidin-2-ylidene)hydrazinocarbonyl]methyl-1H- benzotriazoles 5a-d; 1-[(5-substituted aminothiadiazol-2-yl)methyl]-1H-benzotriazoles 6a-c have been synthesized by cyclization of the key intermediates 1-[(substituted thiocarbamoylhydrazinocarbonyl)methyl]-1H-benzotriazoles 2a-d. Furthermore 1-[(5-substituted aminooxadiazol-2-yl)methyl]-1H-benzotriazoles 7a, b were obtained by one-pot synthesis starting from 1H-benzotriazol-1-acetic acid hydrazide. The antiinflammatory activity of representative compounds was evaluated in vivo against indomethacin as a standard using the sponge implantation model of inflammation in rats. Both non-immunological parameters such as exudate volume, total leucocyte count (TLC), and differential leucocyte count (DLC), and immunological parameters, for example neutrophil phagocytic function by reduced cytochrome C levels, and the assay of interleukin-1 beta (IL-1 beta) levels in drug-pre-treated rats, were determined. The ulcerogenic activity of compounds showing marked antiinflammatory activity was also studied. Compounds 3e, 5b and 5c showed antiinflammatory activity comparable to indomethacin, and they also demonstrated minimum ulcerogenic activity.

Synthesis of some 1,2,4-triazolo [3,4-b] [1,3,4]thiadiazoles as potential anthelmintics.

Two novel series of triazolothiadiazole derivatives were synthesized, namely: 6-substituted-3-(4-substituted phenoxymethyl)-1,2,4-triazolo[3,4- b] [1,3,4]thiadiazoles and 6-mercapto-3-(4-substituted phenoxy-methyl)-1,2,4-triazolo[3,4- b] [1,3,4]thiadiazoles. The anthelmintic activity of representative compounds was studied.

Synthesis of some thiazoline and thiazolidinone derivatives of 1,4-benzoquinone as potential antimicrobial agents.

Three novel series of benzoquinone derivatives were synthesized, namely: N-(3-aryl-4-phenylthiazolin-2-ylidene)-N-(1,4-benzoquinone carbonyl) hydrazines; N-(3-aryl-5-carbethoxy-4-methylthiazolin-2-ylidene)-N-(1,4- benzoquinone carbonyl)hydrazine and N-(3-arylthiazolin-4-one-2-ylidene)-N-(1,4- benzoquinone carbonyl) hydrazines. These series were prepared by oxidation of the new hydroquinone precursors. The antimicrobial activity of representative compounds of benzoquinone, as well as of hydroquinone derivatives was studied.

Potential fungicidal and bactericidal agents. Synthesis of certain 4-(2-amino-1,3,4-thiadiazol-5-yl)quinolines.

The synthesis of some new 4-[2-alkyl (aryl or aralkyl) amino-1,3,4-thiadiazol-5-yl]-2-substituted quinolines is described. IR, UV, NMR and MS data of representative examples are discussed. Most of the compounds prepared showed a reasonable antifungal and antimicrobial activity.

Steroidal derivatives. Part 1: some novel steroidal thiosemicarbazones. Their synthesis, anticancer and endocrinological activities.

The synthesis of several novel thiosemicarbazone derivatives of steroids, including estrogens and androgens, is described. Evaluation of the products in P 388 Lymphocytic Leukemia indicated no anticancer activity. The endocrinological screening showed that estrogenicity is slightly reduced but not abolished in the thiosemicarbazones derived from estrone-3-methyl ether (compounds 1, 2 and 4). The androgenic activity of the thiosemicarbazones derived from testosterone (compounds 7--9) was more pronounced than that of testosterone. Among the same thiosemicarbazone derivatives 7--9, only o-tolyl derivative 8 exhibited anabolic activity.

Synthesis of some quinoline derivatives of potential antiamebic activity.

New compounds derived from cinchoninic acid esters and amides were prepared. The esters are those derived from p-hydroxy-N-methyldichloroacetanilide (diloxanide) whereas the amides are from piperazine whose hydrogen is substituted by a dichloroacetyl group. The dichloroacetamido group is responsible for the amebicidal activity in several related compounds.