Synthesis of substituted 4-aminothieno2,3-d-, 4-aminothieno3,2-d- and 4-aminothieno3,4-dpyrimidines

摘要

A study was carried out on the nucleophilic cleavage of the lactam bond in 4-amino(pyrrolidino, piperidino, morpolino)thieno2,3-d-, -3,2-d-, and -3,4-dpyrimido1,2-bisoquinolin-11-ones. This bond is readily cleaved upon heating in methanolic NaOH at reflux for 1-2 h to give previously unreported 4-amino-2-(o-carboxyphenylmethyl)thienopyrimidines. Replacement of the amine group by an OH group is possible under the reaction conditions, leading to the corresponding, already reported 2-(o-carboxyphenylmethyl)-4- oxothienopyrimidines. Prolonged refluxing (8-12 h) resulted in oxothienopyrimidines as the major products of the transformations of all the thienopyrimido-isoquinolinones studied. Biological activity predictions of these new products were compared in silico.