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 x 10(-5) M).
Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Miyuki
M
Ikeuchi
Masako
M
Ikuta
Miyuki
M
Hariki
Motoki
M
Ikeuchi
Shigeki
S
Maruyama
Mari
M
Nakase
Kumiko
K
Sakamoto
Yasuko
Y
Yoshioka
Aiko
A
Yamauchi
Masaru
M
Kihara
D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004357:Drug Synergism; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001552:Benzazepines; D014662:Vasoconstrictor Agents; D009638:Norepinephrine