Phenanthroindolizidine compound and NF kB inhibitor containing same as active ingredient

Abstract

A novel compound having an excellent NFºB inhibitory effect is provided and specifically disclosed is a compound represented by the following formula (1) or a salt thereof: wherein, R 1 represents a hydrogen atom, a lower alkyl group, a lower alkyloxy group, or a halogen atom; R 2 represents a hydroxyl group, or a lower alkyloky group; R 3 represents a hydrogen atom, a lower alkyl group, or a halogen atom; R 4 represents a hydrogen atom or a lower alkyloxy group; R 5 represents a hydrogen atom, a lower alkyloxy group, a halogen atom, a hydroxyl group, or a methylenedioxy group formed together with R 6 or an isopropylidenedioxy group formed together with R 6 ; R 6 represents a hydrogen atom, a lower alkyloxy group, or a methylenedioxy group formed together with R 5 or an isopropylidenedioxy group formed together with R 5 ; R 7 represents a hydrogen atom or a lower alkyl group; and R 8 represents a hydrogen atom, a hydroxyl group, an amino group, or a lower alkylcarbonyloxy group (excluding the case where R 1 , R 3 , R 4 and R 7 are hydrogen atoms, R 2 and R 8 are hydroxyl groups, and R 5 and R 6 are methoxy groups).

Description

[0001] This case is filed on October 23, 2009 , the application number is 200980141088.6 , the name of the invention is Phenanthrene indorisidine compound and NFκB inhibitor using it as an active ingredient divisional application of the patent application. technical field [0002] 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 [0003] 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). [0004] The heterodimer usually exists in an inactive state combined with inhibitor of NFκB (IκB) in the cytoplasm, but once the cells are stimulated by infla...

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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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