Synthesis and pharmacology of new dithiocarbamic acid esters derived from phenothiazine and diphenylamine.


Karali N. L., Apak I., Ozkirimli S., Gursoy A., Dogan S., Eraslan A., ...Daha Fazla

Archiv der Pharmazie, cilt.332, sa.12, ss.422-6, 1999 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 332 Sayı: 12
  • Basım Tarihi: 1999
  • Dergi Adı: Archiv der Pharmazie
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.422-6
  • İstanbul Üniversitesi Adresli: Evet

Özet

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-methyithiophenyl)-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, H-1 NMR, C-13 NMR, ELMS) methods. The antihistaminic and anticholinergic activities of 4a, 4c, 4e-g, 5a-c, 5e, and 5g were evaluated in comparison with H-1-receptar 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 pA(2) values.