[New analgesically active derivatives of 1-phenyl-5-mercaptotetrazole]

For the investigation of new anti-inflammatory drugs, 1-phenyl-5-mercaptotetrazole (I) was selected as the principal structure. The purpose itself lay in an alkylation of the mercapto group with different remainders. In some cases at the same time a substituent was introduced on the phenyl nucleus in position 1. An alkylation of 1-phenyl-5-mercaptotetrazole with ethyl bromacetate and a subsequent hydrolysis resulted in (1-phenyl-5-tetrazolylthio)acetic acid (II) as well as its chloride and hydrazide. The reaction of chloride with amino acids gave rise to amides III-VII. From hydrazide and phenylisocyanate, 4-chlorphenylisocyanate and phenylisothiocyanate, semicarbazides VIII and IX and thiosemicarbazide X were prepared. Furthermore, a reaction of substituted anilines and 2,3-expoxypropylchloride yielded the pertinent 3-anilino-2-hydroxypropylchlorides XX-XXIII, by which 1-phenyl-5-mercaptotetrazole in the form of the potassium salt was alkylated to compounds XIV-XIX. 1-Phenyl-5-mercaptotetrazole was also alkylated by 2-chlorethanol and the obtained 1-phenyl-5-(2-hydroxyethylthio)tetrazole was esterified by 4-phenylbenzoylchloride and 2-acetoxybenzoyl-chloride giving rise to esters XII and XIII. Finally, three compounds XXIV-XXVI, resulting from an alkylation of 1-phenyl or 1-allylmercaptotrazole by substituted 3-phenoxy-2-hydroxypropylchlorides. In all compounds an orientational acute toxicity higher than 1 g/1 kg p.o. was found. Pharmacological results are shown in Table 2. None of the above-mentioned compounds showed a significant anti-inflammatory efficacy. Analgetic efficacy was manifested in a more marked way; in compound VIII it is comparable with the used standard aminophenazone.