255367-48-7Relevant articles and documents
Synthesis and pharmacology of new dithiocarbamic acid esters derived from phenothiazine and diphenylamine
Karali, Nilguen,Apak, Idil,Oezkirimli, Sumru,Guersoy, Aysel,Dogan, Soenmez Uydes,Eraslan, Aylin,Oezdemir, Osman
, p. 422 - 426 (1999)
2-Methylthio-10-[N,N-disubstituted-thiocarbamoylthio)acetyl]- phenothiazines (4a-g) and N-(3-methylthiophenyl)-N-[(N,N-disubstituted- thiocarbamoylthio)acetyl]phenylamines (5a-g) were synthesized by subsequent treatment of 2-methylthio-10-chloroacetylphenothiazines (1) and N-(3- methylthiophenyl)-N-chloroacetylphenylamine (2) with potassium salts of N,N- disubstituted dithiocarbamic acid derivatives (3a-i). The structures of the compounds were determined by analytical and spectral (IR, 1H NMR, 13C NMR, EIMS) methods. The antihistaminic and anticholinergic activities of 4a, 4c, 4e-g, 5a-c 5e, and 5g were evaluated in comparison with H1-receptor antagonist mepyramine and nonselective cholinergic antagonist atropine. In the first series of experiments, the cumulative concentration-response curves to histamine (10-8-10-4 M) and acetylcholine (10-8-10-4 M) were constructed in separate fundus strips. The test compounds exhibited marked antihistaminic activity at 10-6 M concentration but compounds did not influence acetylcholine induced contractions. Concentration-related experiments carried out on 4g and 5g revealed that a moderate antihistaminic activity was present at 10-7 M concentration of the compounds and became strong at higher concentrations. In the second series of experiments, the cumulative concentration-response curve to histamine (10-9-10-4 M) was constructed in guinea-pig ileum segments. Maximal responses were obtained by 10-6-3 x 10-6 M concentrations of histamine in ileum segments. Similar inhibitions of histamine contractions were also obtained with the test compounds. Their inhibitory effectiveness was evaluated by comparing the pA2 values.
