Synthesis and Biological Activity of Some Novel Thieno[2,3-b]quinoline, Quinolino[3′,2′:4,5] thieno[3,2-d]pyrimidine and Pyrido[2′,3′:4,5] thieno[2,3-b]quinoline Derivatives

Abstract

Thieno [2,3-b] quinoline derivative 5 was synthesized by the cycloalkylation of compound bi 3a with chloro acetonitrile. Interaction of compound 5 with formic acid, formamide, and thioacetamide furnished the corresponding quinolino[3′,2′:4,5]thieno[3,2- d]pyrimidine derivatives 7 , 8 , and 9 , respectively. Also, quinolinothienopyrimidine 11 was obtained in good yield by cyclization of compound 5 with phenyl isothiocyanate under reflux in pyridine. Triethyl orthoformate reacted with compound 5 to form the ethoxymethylene derivative 12 . Refluxing of 5 with acetic anhydride for a short time afforded acetamide derivative 16 , whereas when refluxed for a long time furnished the diacetyl derivative 17 . Fusion of compound 5 with urea and thiourea yielded the corresponding quinolinothienopyrimidines 19 and 20 , respectively. When compound 5 was reacted with urea in the presence of sodium ethoxide, the corresponding ureado derivative 18 was obtained. Treatment of 5 with sulfuric acid at r.t. furnished the novel thienoquinoline 6 , while on heating gave the acid derivative 21 . Pyrido [2′,3′: 4,5]thieno [2,3- d] quinoline 23–25 were synthesized by the interaction of 5 with ethyl cyanoacetate, benzylidenemalononitrile, and acetaldehyde/malononitrile, respectively. On preliminary screening, compounds 22 and 25 exhibited in vitro growth that was inhibitory activity against Saccharomyces Cerevisiae when compared with the standard fungicide Mycostatine. The structure of the biologically active compounds 22 and 25 remain unchanged when exposed to gamma irradiation up to 40 KGy.