Phenanthroindolizidine derivative and nfkb inhibitor containing same as active ingredient

Abstract

A novel compound having an excellent NF?B inhibitory effect. Specifically disclosed is a compound represented by formula (1) or a salt thereof. (In the formula, R1 represents a hydrogen atom, a lower alkyl group or the like; R2 represents a hydrogen atom, a lower alkyl group, a halogen atom or the like; R3 represents a hydrogen atom, a lower alkyl group, a hydroxy group or a halogen atom; R4 represents a hydrogen atom or a lower alkyloxy group; R5 represents a hydrogen atom, a lower alkyloxy group, a halogen atom or a hydroxy group, or alternatively forms a methylenedioxy group or an isopropylidenedioxy group together with R6; R6 represents a hydrogen atom or a lower alkyloxy group, or alternatively forms a methylenedioxy group or an isopropylidenedioxy group together with R5; R7 represents a hydrogen atom or a lower alkyl group; and R8 represents a hydrogen atom, a hydroxy group, an amino group, a lower alkylcarbonyloxy group or a halogen atom.)

Description

technical field [0001] The present invention relates to Nuclear Factor-κB (nuclear factor-κB, hereinafter, sometimes also referred to as NFκB) inhibitors. More specifically, it relates to a novel phenanthrene indorisidine alkaloid compound or a salt thereof that inhibits NFκB, and a drug containing them. Background technique [0002] NFKB exists as a dimer formed by various combinations of NFKB family members p50, p65 / RelA, c-Rel, Rel-B and p52. Among them, the most well-known dimer is a heterodimer formed by a 50 kDa subunit (p50) and a 65 kDa subunit (p65). [0003] The heterodimer usually exists in an inactive state combined with the inhibitor of NFκB (IκB) in the cytoplasm, but once the cells are stimulated by inflammatory cytokines or cell growth factors, etc., it will make IκB through the AKT signal transduction pathway, etc. Kinase activation, which causes the phosphorylation of IκB, the phosphorylated IκB is ubiquitinated and decomposed by the proteasome. As a resu...

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Problems solved by technology

In addition, it is also known that sierphine exhibits strong cytotoxicity, and studies on the synthesis method are also being vigorously carried out (Non-Patent Document 13)

In addition, among the phenanthrene indolizidine alkaloids, it is known that isosilphine represented by the following formula (B) has central nervous system toxicity (Non-Patent Document 14)

In addition, in recent years, it has been known that sylphenine analogues represented by the following formulas (C) and (D) have shown strong cytotoxicity throughout the NCI60 cancer type panel test, and their mechanism of action is different from that of existing anticancer drugs. Tumor agents are different (Non-Patent Document 15)

In addition, it is known that a compound represented by the following formula (E), which is an insect-derived phenanthrene indolizidine alkaloid, has strong cytotoxicity (Non-Patent Document 16)

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