Synthesis and Pharmacological Testing of 1,2,3,4,10,14b-Hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin and Its Enantiomers in Comparison with the Two Antidepressants Mianserin and Mirtazapine

Abstract

The synthesis and resolution of 1,2,3,4,10,14b-hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin (6-methoxymianserin, 6) are described. Furthermore, the in vitro and in vivo effects of 6 and its enantiomers are presented. 6 displayed high affinity for the 5-HT2A/2C receptors, only moderate affinity for the adrenoceptors, and no affinity for the NA reuptake site. Surprisingly, 6 also showed moderate to high affinity for the dopamine D2 receptor, an effect that resides in the (R)-(-)-enantiomer.

Three closely related dibenzazepine carboxylic acids: hydrogen-bonded aggregation in one, two and three dimensions

“…The dibenzo [b,e]azepine ring is an important pharmacophore in drug discovery and many of its derivatives exhibit a broad spectrum of biological activities (Van der Burg et al, 1970;Brogden et al, 1978;Nickolson & Wieringa, 1981;Berger et al, 1989;De Boer et al, 1996;Roeder et al, 1998;André s et al, 2002;Wikströ m et al, 2002). Consequently, a significant number of synthetic methods have been developed for the synthesis of new derivatives of this heterocyclic system (Moriconi & Maniscalco, 1972;Sasakura & Sugasawa, 1981;Stappers et al, 2002).…”

Ring Expansion of a 4,4′-Bipyridyl Derivative into π-Conjugated Azepinoazepines

“…Evaporation of water gave a brown solid, which was washed with acetone (150 mL) and dried under vacuum to afford compound 3 a (0.29 g, 75 %). 1 H 5.18, N 6.86; found: C 64.86, H 5.13, N 6.40. …”

Ring Expansion of a 4,4′‐Bipyridyl Derivative into π‐Conjugated Azepinoazepines

“…Evaporation of water gave a brown solid, which was washed with acetone (150 mL) and dried under vacuum to afford compound 3 a (0.29 g, 75 %). 1 . Keywords: amines · annulenes · fused-ring systems · nitrogen heterocycles · ring expansion…”

“…The electrochemical data also are summarized in Table 2. Azepinoazepines 3 e-3 g with N-halophenyl substituents showed two reduction peaks, which were coupled with anodic peaks E pa (1) and E pa (2). Although the peaks attributed to the twostep electrochemical reduction of the other azepinoazepines 3 a-3 d, 3 h, and 3 i were duplicated, the two anodic peaks were separately observed.…”

“…[1] A large number of reports on synthetic approaches towards these compounds have been published. [2] Metal-complex-catalyzed intramolecular cyclization reactions are useful for the synthesis of azepine derivatives fused with aromatic rings such as benzene, imidazole, and pyridine rings.…”