13-oxidized ingenol derivative and use thereof
AssigneeTianjin Pharmaceutical Da Ren Tang Group Corp., Ltd. Traditional Chinese Medicine Research Institute
InventorsXiao Wu, Qin Pan, Yanyun Li, Yu Yang, Yuzhen Guan, Xiaolei Wu, Chuanteng Sun, Yuan Wang
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Abstract
The present invention relates to a derivative of 13-oxidized ingenol, use thereof in the prevention and/or treatment of a disease associated with proliferation or tumor in a subject, or a cosmetic indication, and use thereof in the prevention and/or treatment of a disease responsive to neutrophil oxidative burst, a disease responsive to a release of IL-8 by keratinocyte, or a disease responsive to induction of necrosis.
Claims8
A compound of Formula (I), or a pharmaceutically acceptable salt, solvate, prodrug, metabolite or crystal form thereof:
- wherein:
- R1 is selected from the group consisting of hydrogen and M-C(O)—, wherein M is selected from the group consisting of hydrogen, 1,3-nonadienyl, C1-C4 linear alkyl, C1-C4 branched alkyl, C4-C9 linear alkyl, C4-C9 branched alkyl, n-decyl, and n-undecyl;
- R2 is Q-C(O)—, wherein Q is selected from the group consisting of methyl, n-propyl,
- and R3 is selected from the group consisting of hydrogen, hydroxyl and X—C(O)—O—, wherein X is selected from the group consisting of methyl, n-propyl, n-pentyl, t-butyl,
- or R1 is M-C(O)—, wherein M is selected from the group consisting of C1-C9 linear or branched alkyl and C2-C11 linear or branched alkenyl containing 1 or 2 carbon-carbon double bonds;
- R2 is selected from the group consisting of hydrogen and Q-C(O)—, wherein Q is selected from the group consisting of methyl, n-propyl, t-butyl,
- and R3 is selected from the group consisting of hydrogen and hydroxyl;
- or R1 is M-C(O)—, and M is n-undecyl;
- R2 is Q-C(O)—, wherein Q is
- and R3 is selected from the group consisting of hydrogen and X—C(O)—O—, wherein X is selected from the group consisting of methyl, n-propyl,
A compound of Formula (I), or a pharmaceutically acceptable salt, solvate, prodrug, metabolite or crystal form thereof:
- wherein:
- R1 is selected from the group consisting of hydrogen and M-C(O)—, wherein M is selected from the group consisting of methyl, n-propyl, n-pentyl, n-heptyl, n-nonyl, 1,3-nondienyl and 1,3,5-nontrienyl;
- R2 is selected from the group consisting of hydrogen and Q-C(O)—, wherein Q is selected from the group consisting of methyl, n-propyl, n-pentyl, t-butyl,
- R3 is selected from the group consisting of hydrogen and X—C(O)—O—, wherein X is selected from the group consisting of methyl, n-propyl, t-butyl, n-pentyl,
- and, when R1 is M-C(O)—, M is methyl or 1,3,5-nontrienyl, R3 is X—C(O)—O— and X is
- R2 is not hydrogen;
- when R1 is M-C(O)—, M is n-nonyl and R3 is CH3—C(O)—O—, R2 is not
- when R1 is hydrogen and R3 is (CH3)3C—C(O)—O—, R2 is not hydrogen or (CH3)3C—C(O)—.
A compound of Formula (I), or a pharmaceutically acceptable salt, solvate, prodrug, metabolite or crystal form thereof:
- wherein:
- R1 is M-C(O)—, and M is n-undecyl;
- R2 is hydrogen;
- R3 is X—C(O)—O—, wherein, X is selected from the group consisting of methyl, n-propyl,
A compound or a pharmaceutically acceptable salt, solvate, prodrug, metabolite or crystal form thereof, wherein the compound is one of the following:
- Name of Compounds
- Structure of Compounds
- 13-O-decanoyl-ingenol
- 13-O-(2′E,4′-E-decadienoyl)-ingenol
- 20-deoxy-13-O-dodecanoyl-ingenol
- 6,7-epoxy-20-deoxy-ingenol
- 6,7-epoxy-20-O-(2,3-dimethylbutyryl)-13-O- dodecanoyl-ingenol
- 3-O-angeloyl-13-hydroxy-ingenol
- 13-O-acetyl-ingenol
- 13-O-n-butanoyl-ingenol
- 13-O-n-hexanoyl-ingenol
- 13-O-n-octanoyl-ingenol
- 3-O-angeloyl-13-O-acetyl-ingenol
- 3-O-acetyl-13-O-dodecanoyl-ingenol
- 3-O-n-butanoyl-13-O-dodecanoyl-ingenol
- 20-O-acetyl-13-O-dodecanoyl-ingenol
- 20-O-n-butanoyl-13-O-dodecanoyl-ingenol
- 20-O-(2,3-dimethylbutyryl)-13-O-dodecanoyl- ingenol
- 20-O-angeloyl-13-O-dodecanoyl-ingenol
- 3,20-O-diangeloyl-13-O-dodecanoyl-ingenol
- 3-O-angeloyl-13-O-hexanoyl-ingenol
- 3-O-angeloyl-13-O-hexaoyl-ingenol
- 3-O-angeloyl-13-O-octanoyl-ingenol
- 3-O-angeloyl-13-O-decanoyl-ingenol
- 3-O-(2,3-dimethylbutenoyl)-13-O- dodecanoyl-ingenol
- 3-O-(3,5-diethylisoxazolyl-4-formyl)-13-O- dodecanoyl-ingenol
- 20-O-tigloyl-13-O-dodecanoyl-ingenol
- 3-O-tigloyl-13-O-dodecanoyl-ingenol
- 20-O-(2,3-dimethylbutenoyl)-13-O-dodecanoyl- ingenol
A compound of Formula (II), or a pharmaceutically acceptable salt, solvate, prodrug, metabolite or crystal form thereof:
- wherein:
- R1 is selected from the group consisting of hydrogen and M-C(O)—, wherein M is selected from the group consisting of hydrogen, 1,3-nonadienyl, C1-C4 linear alkyl, C1-C4 branched alkyl, C4-C9 linear alkyl, C4-C9 branched alkyl, n-decyl, and n-undecyl;
- and R3 is selected from the group consisting of hydrogen, hydroxyl, and X—C(O)—O—, wherein X is selected from the group consisting of methyl, n-propyl, n-pentyl, t-butyl,
- or R1 is M-C(O)—, wherein M is selected from the group consisting of C1-C9 linear or branched alkyl and C2-C11 linear or branched alkenyl containing 1 or 2 carbon-carbon double bonds;
- and R3 is selected from the group consisting of hydrogen and hydroxyl;
- or R1 is M-C(O)—, and M is n-undecyl;
- and R3 is selected from the group consisting of hydrogen and X—C(O)—O—, wherein X is selected from the group consisting of methyl, n-propyl,
Dependencies are inferred from the claim text.