[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.
Kejha
J
J
Výzkumný ústav pro farmacii a biochemii, Praha.
Sluková
D
D
Brůnová
B
B
Maturová
E
E
Grimová
J
J
D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004487:Edema / Q000188:drug therapy; D005260:Female; D006863:Hydrogen-Ion Concentration; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D013777:Tetrazoles / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013777:Tetrazoles; C025766:1-phenyl-5-mercaptotetrazole
Nové analgeticky úcinné deriváty 1-fenyl-5-merkaptotetrazolu.