Indole alkaloid and preparation method and use thereof

A pharmaceutical composition comprising a compound represented by formula I, or the pharmaceutically acceptable salt thereof, or ane isomer thereof, and a pharmaceutical excipient;

• wherein the formula I is shown as follows:
• in the formula:
• X is O or —NR1;
• R1 is hydrogen, unsubstituted or R1-1 substituted C1-6 alkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, and C3-10 cycloalkyl-(C1-4 alkyl)- or C6-12 aryl-(C1-4 alkyl)-;
• R1-1 is halogen or hydroxyl;
• Y is —(CH2)m—;
• m is an integer from 1 to 6;
• Z is a single bond,
• R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 are each independently selected from hydrogen, unsubstituted or R3-1 substituted C1-6 alkyl, C6-10 aryl, unsubstituted or R3-2 substituted C6-12 aryl-(C1-4 alkyl)-, heteroaryl, or heteroaryl-(C1-4 alkyl)-;
• and the heteroaryl is 5-10 membered heteroaryl;
• R3-1 is hydroxyl, carboxyl, amino, sulfhydryl, —(C═O)NR3-1-1, or —NH(C═NH)NH2;
• R3-1-1 is hydrogen or C1-4 alkyl;
• R3-2 is halogen or hydroxyl;
• R is hydrogen, hydroxyl, C1-6 alkoxy or
• R2 is C1-6 alkyl or hydrogen;
• n is an integer from 0 to 500;
• and
• is polyethylene glycol (PEG) with a linear, tree, star or hyperbranched structure comprising —(OCH2CH2)n;
• wherein the tree-shaped PEG is a polymer with a highly symmetrical, tree-like architecture, synthesized layer by layer from a central core to form a precise, multi-branched structure;
• the star-shaped PEG is a branched polymer architecture in which multiple linear PEG chains emanate from a central core molecule, creating a star-like or radial topology;
• the hyperbranched PEG is a three-dimensional, globular polymer obtained through a one-step synthesis;
• it possesses a densely yet irregularly branched structure, lacking the perfect symmetry of dendritic polymers.

A method for treating a disease by administrating a compound represented by formula I or a pharmaceutically acceptable salt thereof or an isomer thereof to a subject in need, wherein the disease is selected from the group consisting of type 1 diabetes, type 2 diabetes, diabetic peripheral neuropathy, diabetic foot and pulmonary fibrosis disease;

• wherein the formula I is shown as follows:
• in the formula:
• X is O or —NR1;
• R1 is hydrogen, unsubstituted or R1-1 substituted C1-6 alkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, and C3-10 cycloalkyl-(C1-4 alkyl)- or C6-12 aryl-(C1-4 alkyl)-;
• R1-1 is halogen or hydroxyl;
• Y is —(CH2)m—;
• m is an integer from 1 to 6;
• Z is a single bond,
• R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 are each independently selected from hydrogen, unsubstituted or R3-1 substituted C1-6 alkyl, C6-10 aryl, unsubstituted or R3-2 substituted C6-12 aryl-(C1-4 alkyl)-, heteroaryl, or heteroaryl-(C1-4 alkyl)-;
• and the heteroaryl is 5-10 membered heteroaryl;
• R3-1 is hydroxyl, carboxyl, amino, sulfhydryl, —(CO)NR3-1-1, or —NH(C═NH)NH2;
• R3-1-1 is hydrogen or C1-4 alkyl;
• R3-2 is halogen or hydroxyl;
• R is hydrogen, hydroxyl, C1-6 alkoxy or
• R2 is C1-6 alkyl or hydrogen;
• n is an integer from 0 to 500;
• and
• is polyethylene glycol (PEG) with a linear, tree, star or hyperbranched structure comprising —(OCH2CH2)n;
• wherein the tree-shaped PEG is a polymer with a highly symmetrical, tree-like architecture, synthesized layer by layer from a central core to form a precise, multi-branched structure;
• the star-shaped PEG is a branched polymer architecture in which multiple linear PEG chains emanate from a central core molecule, creating a star-like or radial topology;
• the hyperbranched PEG is a three-dimensional, globular polymer obtained through a one-step synthesis;
• it possesses a densely yet irregularly branched structure, lacking the perfect symmetry of dendritic polymers.