title: Design, synthesis, and preliminary activity evaluation of novel pyrimidine derivatives as acid pump antagonists.
abstract: Acid-related diseases of the upper gastrointestinal tract, especially gastroesophageal reflux disease (GERD), remain a widespread problem worldwide. In this paper, we reported the design, synthesis, and preliminary gastric antisecretory activity evaluation of novel pyrimidine derivatives as acid pump antagonists. The gastric antisecretory activity assay results showed that all compounds displayed potent gastric antisecretory activity when gastric secretion was stimulated by histamine. The most potent compound 5g exhibited even similar gastric antisecretory activity compared with the control revaprazan, and the relative inhibition rate was 93.0%, which was worthy of further investigation.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44 West Culture Road, Ji'nan, Shandong, 250012, China; Shouguang Fukang Pharmaceutical Co., Ltd., 5 xueyuan east street, Shouguang, Shandong, 262799, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Song
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Zhang
authors.forename: Shutao
authors.initials: S
authors.lastname: Li
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D054328:Proton Pump Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
chemical_list: C000602519:2-(2-(1H-benzo(d)imidazol-2-ylthio)pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline; D001562:Benzimidazoles; D007546:Isoquinolines; D054328:Proton Pump Inhibitors; D011743:Pyrimidines; D011744:Pyrimidinones; D044005:Tetrahydroisoquinolines; C108798:YH 1885
keywords: acid pump antagonists; bioisosterism; gastric antisecretory activity; pyrimidine derivatives; synthesis