Leishmaniasis and malaria are serious public health problems in tropical and sub-tropical regions worldwide. Development of drug-resistant strains has disrupted efforts to control the spread of these diseases in the world. The conventional antiparasitic chemotherapy still suffers from side effects and drug resistance. Therefore, the development of novel antimalarial and leishmanicidal drugs remains a critical topic to combat against these diseases. Five-membered heterocyclic systems have possessed antiparasitic activity such as thiadiazole scaffold which is a prevalent and an important heterocyclic ring. For this purpose, the authors introduce a series of synthetic thiadiazole derivatives with antileishamanial activity. Also, the authors searched a number of sources and articles to find thiadiazole derivatives with antileishamnial and antimalarial activity. Then all of the findings were reviewed. 5-nitroheteroaryl-1, 3, 4-Thiadiazole derivatives with different substituents at position 2 of the thiadiazole ring (8, 10-11) presented the best antileishmanial activity with low toxicity compared with reference drug. Also, 1, 3, 4-thiadiazole-2-sulfonamide derivative (18) showed excellent inhibitory activity against pfCA as a special enzyme in Plasmodium falciparum. Thiadiazole scaffold has the suitable physicochemical and pharmacokinetic properties and still stays as a therapeutic target for the development of a novel lead in the medicinal chemistry. Therefore, the current review provides a brief summary of medicinal chemistry of thiadiazole ring and introduces novel leads possessing this nucleus with antimalarial and antileishmanial activities.

Starting from readily, available 2-substituted-4-methylthiazole-5-carboxylic acid hydrazide (1), The title compounds were prepared The reaction of compound 1 (R = CN3) with formic acid yielded 1-(formyl)-2-(2,4-dimethylthiazole-5-carboxyl) hydrazine (2). Refluxing the latter with phosphorous pentasulfide in xylene afforded compound 3, the reaction of compound 2 with phosphorous pentoxide afforded compound 4 Reaction of compound 1 with substituted isothiocyanates followed by cyclization. of the intermediate 5 in basic medium gave 4-alkyl-5-(2-substituted-4-methyl-5-thiazolyl)-2,4-dihydro-3H-1,2,4-tria zole-3-thione (6). Alkylation of compound 6 followed by subsequent oxidation of intermediate 7 gave compound 8. The reaction of acid chloride II with hydrazide 12 afforded compound IJ which was cyclized by P2S5 or P2O5 to compounds 14 or 15 respectively Compounds 3 and 14 showed significant activities against E. Coil and Bacillus Subtilis.

A novel and simple method for rapid conversion of thioamides to the corresponding 1,2,4-thiadiazole derivatives was developed. It was shown that, thioamides undergo clean and efficient oxidation and cyclization in their conversion to 1,2,4- thiadiazoles using N-benzyl-DABCO-tribromide in wet solid-solid conditions.

4, 5-diaryl-1, 2, 3-thiadiazoles show biological activities. They have been as angiotensin II antagonists, PPARα agonists, antimicrobial and antitumor agents, anticonvulsants, anti-inflammatory agents, insecticides and fungicides. In this study 4-(4- bromophenyl)-5-phenyl-1, 2, 3-thiadiazole was synthesized by two methods and the results were compared. In the first method, bromophenyl was used as a starting material but in the other method, bromination reaction was used in the final step for a bromo substitution. Results have shown that the first step had higher yield and fewer steps. These synthesizes were confirmed by wet elemental analysis, IR and 1H NMR spectroscopies.