[Structure-activity analysis of analgetically active sulphur-containing pyridazines (author's transl)].
The distribution coefficients in n-octanol/water and the RM values in two different solvents have been determined for 12 newly synthetized sulphur-containing pyridazines. The establishment of dose-effect curves by means of three screening methods (writhing syndrome, tail flick test and hot-plate test) permitted to estimate the analgetic activities of the substances under investigation. Regression analyses revealed a highly significant correlation between the ED50 values and the RM values of the pyridazines in butanol/glacial acetic acid/water. The greatest analgetic effect was observed with compounds, the RM values of which tended to 0. To complement this study, the LD50 values and the side-effects on the central nervous system wee considered, too. There was no correlation between the LD50 values and the distribution coefficients; however, a low-significant correlation existed between the side-effects on the central nervous system (as measured by the failure rates in the rotarod test) and the distribution coefficients. In summary, the results hitherto obtained permit to conclude that four of the twelve pyridazines excel by "favourable" analgetic activities. Considering the therapeutic quotients, further investigations, especially of one of these compounds, 3-amino-4-mercapto-6-methylpyridazine, seem justified.
D000700:Analgesics; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D008297:Male; D051379:Mice; D011724:Pyridazines / Q000494:pharmacology* / Q000633:toxicity; D012995:Solubility; D013329:Structure-Activity Relationship
D000700:Analgesics; D011724:Pyridazines
Struktur-Wirkungs-Analyse von analgetisch wirksamen schwefelhaltigen Pyridazinen.