Glucocorticoid receptor agonist and conjugate thereof

A compound of formula I, a pharmaceutically acceptable salt, a stereoisomer, a tautomer, a polymorph, a solvate, an N-oxide, an isotope labeled compound, a metabolite, or a prodrug thereof:

• wherein,
• R1 is each independently selected from a group consisting of hydrogen, halogen, —NRaRb, hydroxyl, cyano, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyl, C1-6 alkyl substituted with one or more hydroxyls, C1-6 alkoxy and C1-6 haloalkyl;
• preferably, R1 is each independently selected from a group consisting of hydrogen, halogen, —NRaRb, hydroxyl, C1-6 alkyl, C1-6 alkyl-OH and C1-6 alkoxy;
• preferably, R1 is each independently selected from a group consisting of hydrogen, fluorine, chlorine, amino, hydroxyl, methyl, ethyl and hydroxymethyl;
• preferably, R1 is each independently selected from a group consisting of hydrogen, fluorine, amino, hydroxyl, methyl, ethyl and hydroxymethyl;
• R2 is selected from a group consisting of hydrogen, C1-6 alkyl, hydroxyl and C1-6 alkoxy;
• preferably, R2 is selected from a group consisting of hydrogen, methyl, hydroxyl and methyoxy;
• preferably, R2 is selected from a group consisting of hydrogen and methyl;
• ring A is selected from a group consisting of a single bond, a C6-10 aromatic ring and a 5-6 membered heteroaromatic ring;
• preferably, ring A is selected from a group consisting of a single bond, a benzene ring, and a 5-6 membered heteroaromatic ring;
• preferably, ring A is selected from a group consisting of a single bond, a benzene ring, a pyridine ring, a furan ring and a thiophene ring;
• X is selected from a group consisting of a single bond, C1-6 alkylene, C3-6 cycloalkylene, C2-6 alkenylidene, C2-6 alkynylidene and —NRa—;
• preferably, X is selected from a group consisting of a single bond, methylene, ethylene, propylene, butylene, cyclopropylene, cyclohexylene, ethenylidene and imino;
• preferably, X is selected from a group consisting of a single bond, methylene, ethylene, propylene, butylene, 1,1-cyclopropylene, 1,2-cyclopropylene, 1,4-cyclohexylene and ethenylidene;
• Y is selected from a group consisting of —O— and —S—;
• Z is selected from a group consisting of hydroxyl, halogen and cyano;
• preferably, Z is selected from a group consisting of hydroxyl, fluorine, chlorine and cyano;
• Q1 and Q2 are each independently selected from a group consisting of hydrogen and halogen;
• preferably, Q1 and Q2 are each independently selected from a group consisting of hydrogen, fluorine and chlorine;
• preferably, Q1 is selected from a group consisting of hydrogen and fluorine, and Q2 is fluorine;
• m is selected from a group consisting of 1, 2, 3, 4 and 5;
• preferably, m is selected from a group consisting of 1 and 2;
• n is selected from a group consisting of 1 and 2;
• preferably, n is 1;
• Ra and Rb are each independently selected from a group consisting of hydrogen and C1-6 alkyl;
• provided that:
• when R1 is each independently selected from a group consisting of halogen, amino and methyl, m is 2, R2 is methyl, X is a single bond, Y is —S—, Z is fluorine, n is 1, Q1 is hydrogen or fluorine, and Q2 is fluorine, ring A is not phenyl;
• when ring A is a single bond, R1 is not hydrogen or C1-6 alkyl;
• and
• when ring A is a 5-6 membered heteroaromatic ring, R1 is hydrogen and R2 is C1-6 alkyl, Q1 is not halogen.