Small molecule compound inhibiting signal transmission path of TLR7 and TLR9 and use thereof
AssigneeAjou University Industry-Academic Cooperation Foundation
InventorsSangdun Choi, Haseeb Muhammad, Mahesh Patra, Yang-Seon Choi
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Abstract
A compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof is disclosed. The compound inhibits a toll-like receptor (TLR) signaling pathway. A composition containing the compound and uses thereof are disclosed. The novel compound blocks the TNF-α secretion by inhibiting the expression and activation of NF-κB- and MAPK-related proinflammatory genes, and thus can be utilized as a therapeutic agent for many autoimmune diseases, such as systemic lupus erythematosus, psoriasis and psoriatic arthritis, associated with a hyperactivity of a nucleic acid:
Claims20
A compound of Chemical Formula 1 below or a pharmaceutically acceptable salt thereof:
- wherein in Chemical Formula 1,
- R1 to R5 are each independently a hydrogen atom, straight or branched alkyl, amino, hydroxy, halogen, nitrile group, nitro group, cycloalkyl, haloalkyl, allyl, alkoxy, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, alkylarylcarbonyl, alkoxycarbonyl, cycloalkoxy, substituted or unsubstituted aryl, heteroaryl, heterocycloalkyl, aryloxy, alkoxyheteroaryl, heteroaryloxyalkyl, alkylheteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, alkylester, alkylamide, or acryl,
- wherein the alkyl is C1-30 alkyl, the alkoxy is C1-30 alkoxy, the cycloalkyl is C3-30 cycloalkyl, the allyl is C2-30 allyl, the aryl is C6-30 aryl, and the heteroaryl and heterocycloalkyl comprise a heteroatom selected from the group consisting of fluorine (F), oxygen (O), sulfur(S), and nitrogen (N),
- with the proviso that the compound, in which R1 and R3 are a hydrogen, R2 or R4 is methyl and R5 is methoxyphenyl, is excluded.
A composition comprising a compound of Chemical Formula 1 below or a pharmaceutically acceptable salt thereof:
- wherein in Chemical Formula 1,
- R1 to R5 are each independently a hydrogen atom, straight or branched alkyl, amino, hydroxy, halogen, nitrile group, nitro group, cycloalkyl, haloalkyl, allyl, alkoxy, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, alkylarylcarbonyl, alkoxycarbonyl, cycloalkoxy, substituted or unsubstituted aryl, heteroaryl, heterocycloalkyl, aryloxy, alkoxyheteroaryl, heteroaryloxyalkyl, alkylheteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, alkylester, alkylamide, or acryl,
- wherein the alkyl is C1-30 alkyl, the alkoxy is C1-30 alkoxy, the cycloalkyl is C3-30 cycloalkyl, the allyl is C2-30 allyl, the aryl is C6-30 aryl, and the heteroaryl and heterocycloalkyl comprise a heteroatom selected from the group consisting of fluorine (F), oxygen (O), sulfur(S), and nitrogen (N),
- with the proviso that the compound, in which R1 and R3 are a hydrogen, R2 or R4 is methyl and R5 is methoxyphenyl, is excluded.
A method for treating an autoimmune disease in a subject in need thereof, comprising administering to the subject a composition comprising a compound of Chemical Formula 1 below or a pharmaceutically acceptable salt thereof:
- wherein in Chemical Formula 1,
- R1 to R5 are each independently a hydrogen atom, straight or branched alkyl, amino, hydroxy, halogen, nitrile group, nitro group, cycloalkyl, haloalkyl, allyl, alkoxy, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, alkylarylcarbonyl, alkoxycarbonyl, cycloalkoxy, substituted or unsubstituted aryl, heteroaryl, heterocycloalkyl, aryloxy, alkoxyheteroaryl, heteroaryloxyalkyl, alkylheteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, alkylester, alkylamide, or acryl,
- wherein the alkyl is C1-30 alkyl, the alkoxy is C1-30 alkoxy, the cycloalkyl is C3-30 cycloalkyl, the allyl is C2-30 allyl, the aryl is C6-30 aryl, and the heteroaryl and heterocycloalkyl comprise a heteroatom selected from the group consisting of fluorine (F), oxygen (O), sulfur(S), and nitrogen (N),
- wherein the autoimmune disease is associated with toll-like receptor (TLR) signaling pathway.
A method for treating an inflammatory disease in a subject in need thereof, comprising administering to the subject a composition comprising a compound of Chemical Formula 1 below or a pharmaceutically acceptable salt thereof:
- wherein in Chemical Formula 1,
- R1 to R5 are each independently a hydrogen atom, straight or branched alkyl, amino, hydroxy, halogen, nitrile group, nitro group, cycloalkyl, haloalkyl, allyl, alkoxy, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, alkylarylcarbonyl, alkoxycarbonyl, cycloalkoxy, substituted or unsubstituted aryl, heteroaryl, heterocycloalkyl, aryloxy, alkoxyheteroaryl, heteroaryloxyalkyl, alkylheteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, alkylester, alkylamide, or acryl,
- wherein the alkyl is C1-30 alkyl, the alkoxy is C1-30 alkoxy, the cycloalkyl is C3-30 cycloalkyl, the allyl is C2-30 allyl, the aryl is C6-30 aryl, and the heteroaryl and heterocycloalkyl comprise a heteroatom selected from the group consisting of fluorine (F), oxygen (O), sulfur(S), and nitrogen (N),
- wherein the inflammatory disease is associated with the toll-like receptor (TLR) signaling pathway.
A method for inhibiting a toll-like receptor (TLR) in a subject in need thereof, comprising administering an effective amount of a compound of Chemical Formula 1 below or a pharmaceutically acceptable salt thereof to the subject:
- wherein in Chemical Formula 1,
- R1 to R5 are each independently a hydrogen atom, straight or branched alkyl, amino, hydroxy, halogen, nitrile group, nitro group, cycloalkyl, haloalkyl, allyl, alkoxy, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, alkylarylcarbonyl, alkoxycarbonyl, cycloalkoxy, substituted or unsubstituted aryl, heteroaryl, heterocycloalkyl, aryloxy, alkoxyheteroaryl, heteroaryloxyalkyl, alkylheteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, alkylester, alkylamide, or acryl,
- wherein the alkyl is C1-30 alkyl, the alkoxy is C1-30 alkoxy, the cycloalkyl is C3-30 cycloalkyl, the allyl is C2-30 allyl, the aryl is C6-30 aryl, and the heteroaryl and heterocycloalkyl comprise a heteroatom selected from the group consisting of fluorine (F), oxygen (O), sulfur(S), and nitrogen (N).
A method for treating a toll-like receptor (TLR) signaling pathway-associated disease or disorder in a subject in need thereof, comprising administering an effective amount of a compound of Chemical Formula 1 below or a pharmaceutically acceptable salt thereof to the subject:
- wherein in Chemical Formula 1,
- R1 to R5 are each independently a hydrogen atom, straight or branched alkyl, amino, hydroxy, halogen, nitrile group, nitro group, cycloalkyl, haloalkyl, allyl, alkoxy, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, alkylarylcarbonyl, alkoxycarbonyl, cycloalkoxy, substituted or unsubstituted aryl, heteroaryl, heterocycloalkyl, aryloxy, alkoxyheteroaryl, heteroaryloxyalkyl, alkylheteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, alkylester, alkylamide, or acryl,
- wherein the alkyl is C1-30 alkyl, the alkoxy is C1-30 alkoxy, the cycloalkyl is C3-30 cycloalkyl, the allyl is C2-30 allyl, the aryl is C6-30 aryl, and the heteroaryl and heterocycloalkyl comprise a heteroatom selected from the group consisting of fluorine (F), oxygen (O), sulfur(S), and nitrogen (N),
- wherein the TLR signaling pathway-associated disease or disorder is inflammation or autoimmune disease.
Dependencies are inferred from the claim text.