1204575-21-2Relevant academic research and scientific papers
New pyridobenzoxazepine derivatives derived from 5-(4-methylpiperazin-1-yl) -8-chloro-pyrido[2,3-b ][1,5]benzoxazepine (JL13): Chemical synthesis and pharmacological evaluation
Liégeois, Jean-Fran?ois,Deville, Marine,Dilly, Sébastien,Lamy, Cédric,Mangin, Floriane,Résimont, Mélissa,Tarazi, Frank I.
experimental part, p. 1572 - 1582 (2012/04/17)
A series of new pyridobenzoxazepine derivatives with various heterocyclic amine side chains were synthesized to explore two main parameters related to the distal basic nitrogen. These compounds were tested for their affinity for dopamine D2L and D4, serotonin 5-HT1A and 5-HT2A, and adrenergic α2A receptors in comparison with 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine, JL13 (1), and other diarylazepine derivatives. In terms of multireceptor target strategy, 2 and 5 present the most promising in vitro binding profile. Bulky, polar, and more flexible side chains are not favorable in this context. Compounds 2 and 5 were tested in adult rats to evaluate their long-term effects on dopamine and serotonin receptors density in different brain areas. Similar to 1 and other second-generation antipsychotic drugs, repeated treatment with 2 significantly increased D1 and D4 receptors in nucleus accumbens and caudate putamen and D2 receptors in medial prefrontal cortex and hippocampus, while 5 significantly increased D2 and D 4 receptors in nucleus accumbens. In addition, 2 increased 5-HT 1A and decreased 5-HT2A receptors in cerebral cortex. In contrast, 5 did not alter levels of any 5-HT receptor subtype in any brain region examined. These results encourage further development of 2 as a novel second-generation antipsychotic agent.
