Синтез новых производных 11h-индено[1,2-b]-хиноксалина как перспективных ингибиторов Jnk (c-Jun n-терминальной киназы)

Abstract

Various quinoxalines show biological activity and have such properties as antiviral, antibacterial, antimicrobial, anti-inflammatory, anticancer, antidepressant, vermicidal, and act as inhibitors of kinases [1]. JNK family enzymes (C-Jun N-terminal kinase) are involved in an embryonal heart development, a regulation of metabolism and normal functioning of a myocardium. Besides, they play an important role in the signaling pathways which lead to apoptosis and necrosis and, also, they regulate processes by which damage of brain neurons and cardiomyocytes during ischemia are depended on. In this regard, the development of specific inhibitors of JNK is a relevant objective of medical chemistry. Derivants with 11H-indeno[1,2-b]-quinoxaline system are described in literature, but there is not a lot of them. For example, it is known only 45 replaced (generally - methyl, nitro - alkoxy-, carboxyl groups) 11Hindeno[1,2-b]- quinoxaline-11-ones according to Reaxys base. For some of them provided data about inhibition of enzymes (glucosidase, SYK kinase) anticarcinogenic activity. Someone systematic researches on influence of the nature of the substituting group on activity and bioavailability of 11H-indeno [1,2-b]- quinoxalines are still unknown of carrying out. The expected results are urgent to from the fundamental and practical point of view. Methods of synthesis of new derivants of 11H-indeno[1,2-b] -quinoxaline will be developed, which will make a contribution to chemistry of the condensed heterocyclic systems. The obtained data will make a contribution to rational design of medicines for treatment of these diseases. Existence in synthesizable molecules of ionizable and biocompatible group does them by potentially more bioavailable and will give an opportunity for creation on their basis of pharmaceuticals.