SYNTHESIS AND RADIOLIGAND ACTIVITY OF HYDROGENATED AZEPINO(4,3-b)INDOLES

Indole-containing compounds are found to interact with many therapeutically relevant targets that belong to different types of cell membrane receptors. They represent a very promising class of potential drugs. The synthesis of novel 1,2,3,4,5,5a,6,10b-octahydroazepino[4,3-b]indoles and their interaction profiles measured on a series of 66 therapeutic targets including receptors, enzymes, and neuromediator transporters are described. The target recognition patterns of the compounds are compared with those of their bioisosteric analogs, diazoline (I) and Dimebon TM (II), which are 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles, in addition with those of 1,2,3,4,5,6-hexahydroazepino[4,3-b]indoles VIII and X. We show that different therapeutic targets exhibit different levels of sensitivity toward cis- and trans-configurations of the new structures. The new compounds exhibit affinity predominantly toward histamine H1 and serotonin 5-HT2C receptors.