Abstract: Here the report antiulcer activity of some 2,6-bis substituted pyrimidothienopyridine (1-9). Eighteen pyrimidothienopyridine derivatives were synthesized and screened as analgesic, anticonvulsant and antiparkinsonian agent before. Many pyrimidines derivatives were synthesized and showed wide diversity of excellent biological activities, the most interesting one amongest these activities the antiulcer activates. It was proven that the antiulcer activities of many pyrimidines derivatives were due to their proton Pump Inhibitor Activities (PPI). Herein and due to structure similarity between the compounds in study and some pyrimidines derivatives showed potent antiulcer activities, the antiulcer activities of these compounds were evaluated using pyloric ligation ulcer model. All the tested compounds showed potent antiulcerogenic activities and the potency descending order was 6b, 6a, 5b, 5a, 7b, 7a, 9b, 9a, 8b, 8a, 2b, 2a, 3b, 3a, 4b, 4a, 1b and 1a. To specify the accurate mechanism of antiulcer activity, many animal models were used the only one that give fruit results was H+/K+-ATPase inhibition in membrane vesicles of stomach mucosa that proved all antiulcer activities of the tested compounds accomplished via H+/K+-ATPase (proton pump) inhibition activities.