Synthesis and Antiulcer Activity of 5,11-Dihydrobenzoxepinopyridines

Article abstract of DOI:10.1021/jm00399a016

A series of substituted 5,11-dihydro<1>benzoxepino<3,4-b>pyridines was synthesized and evaluated for antiulcer activity in water immersion/restrained stress ulcer assay in rats.Structure-activity relationships are described.Most of the tested compounds exhibited low affinity to the muscarinic acetylcholine receptor.The molecular features for the best activities are the 2-(diethylamino)ethylenediamine group at the 5-position of the oxepin ring and an oxepin skeleton rather than a thiepin or a pyran skeleton.Methyl and chlorine substitution on the benzene ring reduced the activity.Compound 11, 5-<<2-(diethylamino)ethyl>amino>-5,11-dihydro<1>benzoxepino<3,4-b>pyridine trihydrochloride was selected for further evaluation.Synthesis and antiulcer activity of optically active 11 is described.There were no statistically significant differences between (+)-, (-), and (+/-)-11.Compound 11 showed weak antisecretory activity in pylorus-ligated rats.It is now under clinical evaluation as KW 5805.