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™ (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.
Similar content being viewed by others
References
A. V. Ivashchenko, O. D. Mit’kin, M. G. Kadieva, and E. S. Tkachenko, Usp. Khim., 79(4), 325–347 (2010).
Ger. Pat. 930,444 (1955); Chem. Abstr., 52, 113832 (1958).
P. Ya. Gaponyuk and V. I. Oivin, Farmakol. Toksikol., 31, 62–67 (1968).
K. S. Shadurskii, T. Yu. Il’ichenok, F. A. Trofimov, et al., Farmakol. Toksikol., 32, 482–487 (1969).
USSR Pat. 1,138,164 (1985); Chem. Abstr., 102, 198010 (1985).7. A. V. Ivashchenko, O. D. Mit’kin, I. M. Okun’, et al., Eksp. Klin. Farmakol., 73(3), 28–30 (2010).
A. V. Ivachtchenko, E. B. Frolov, O. D. Mitkin, et al., Bioorg. Med. Chem. Lett., 19(12), 3183–3187 (2009).
A. V. Ivashchenko, E. B. Frolov, O. D. Mit’kin, et al., Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol., 52(10), 66–72 (2009).
A. V. Ivashchenko, E. B. Frolov, O. D. Mit’kin, et al., Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol., 52(10), 73–77 (2009).
A. V. Ivashchenko, O. D. Mit’kin, E. B. Frolov, et al., Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol., 52(10), 88–93 (2009).
A. V. Ivachtchenko, E. B. Frolov, O. D. Mitkin, et al., Lett. Drug Des. Discovery, 7(6), 446–451 (2010).
A. V. Ivashchenko, M. G. Kadieva, D. V. Kravchenko, et al., Eksp. Klin. Farmakol., 73, 28–30 (2010).
A. V. Ivachtchenko, O. D. Mitkin, E. B. Frolov, et al., Chem. Heterocycl. Compd., 2, 209–220 (2010).
RF Pat. 2,374,245 (2009); Byull. Izobret., No. 33 (2009).
I. Okun, S. Tkachenko, A. Khvat, et al., Curr. Alzheimer Res., 7(2), 97–112 (2010).
Y. Nagai, A. Irie, Y. Masuda, et al., J. Med. Chem., 22, 677–683 (1979).
R. Sarges, H. R. Howard, K. M. Donahue, et al., J. Med. Chem., 29, 8–16 (1986).
J. G. Berger, F. Davidson, and G. E. Langford, J. Med. Chem., 20, 600–605 (1977).
B. Everitt, Cluster Analysis, Gower Publishing Co, Hampshire (1980).
A. V. Ivachtchenko, E. B. Frolov, O. D. Mitkin, et al., Bioorg. Med. Chem. Lett., 19, 3183–3187 (2009).
Author information
Authors and Affiliations
Additional information
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 46, No. 2, pp. 38 – 48, February, 2012.
Rights and permissions
About this article
Cite this article
Mit’kin, O.D., Ivachtchenko, A.V., Frolov, E.B. et al. Synthesis and radioligand activity of hydrogenated azepino[4,3-b]indoles. Pharm Chem J 46, 103–113 (2012). https://doi.org/10.1007/s11094-012-0742-z
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-012-0742-z