Synthesis and Pharmacological Evaluation of New 1-Hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines as Norepinephrine Potentiators

4-Hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (PI-OH) (1a) and its derivatives form a new class of compounds which possess norepinephrine (NE) potentiating activity. As a new series of compounds, 1-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines (2a—f) were synthesized by the intramolecular Barbier reaction of N-[2-(2-iodophenyl)ethyl]phenacylamines (6a—f) with n-BuLi as a key reaction step. The potentiating activities of the benzazepines 2a—f on the contraction of rat anococcygeus muscle induced by NE were tested. Among the compounds tested in this study, compound 2a showed moderate potentiating activity (the activity ratio was 7.3-fold at 3×10−5 M).