Phenyl [a]indole[2,3-g]quinolizine compounds, preparation method therefor, pharmaceutical composition, and applications thereof

A phenyl [a] indole [2,3-g] quinazine compound of formula (I), or an enantiomer, diastereomer, racemate, and mixture thereof, a pharmaceutically acceptable salt, crystalline hydrate and solvate thereof,

• wherein R1 and R2 are each independently selected from the group consisting of hydrogen, deuterium, tritium, halogen, a substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heterocyclic ring, substituted or unsubstituted C1-C6 alkylphenyl, substituted or unsubstituted C1-C6 alkyl (5-7 membered heteroaryl), substituted or unsubstituted C3-C12 cycloalkyl, substituted or unsubstituted C2-C10 acyl, substituted or unsubstituted C2-C10 ester group, amino group, substituted or unsubstituted C1-C6 amide group, —SO2R9, —OSO2R9, —OCOR9;
• and R1 and R2 are not both hydrogen;
• or the R1 and R2 and the adjacent —(CH2)n-O and C═C together form a substituted or unsubstituted 5-7 membered heterocyclic ring, wherein the heterocyclic ring is an aromatic heterocyclic ring;
• R3 and R4 are each independently selected from the group consisting of hydrogen, deuterium, tritium, halogen, amine, hydroxy, a substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heterocyclic ring, substituted or unsubstituted C1-C6 alkylphenyl, substituted or unsubstituted C3-C12 cycloalkyl, substituted or unsubstituted C2-C10 acyl, substituted or unsubstituted C2-C10 ester group, amino, C1-C6 alkylamino, substituted or unsubstituted C1-C6 amide group, —SO2R9, —OSO2R9, —OCOR9;
• R5, R6, R7 and R8 are each independently selected from the group consisting of hydrogen, deuterium, tritium, halogen, hydroxy, a substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C1-C6 alkylphenyl, substituted or unsubstituted C1-C6 alkyl-(5-7 membered heteroaryl), substituted or unsubstituted C3-C12 cycloalkyl, cyano, nitro, carboxyl, sulfydryl, —NR9R10, —NCOR9R10, —SO2R9, —SO2NR9R10, —OSO2R9, or —OCOR9;
• R9 and R10 are independently hydrogen, deuterium, tritium, halogen, an unsubstituted or 1-3 halogen substituted C1-C6 alkyl, or C3-C6 cycloalkane unsubstituted or substituted by 1-3 halogens, C6-C10 aryl unsubstituted or substituted by 1 to 3 halogens, C1-C3 alkyl-(C6-C10 aryl) unsubstituted or substituted by 1-3 halogens, 5-7 membered heteroaryl unsubstituted or substituted by 1-3 halogens;
• and when both of R3 and R4 are hydrogen, at least one of R1, R2, R6, or R7 is selected from the group consisting of an unsubstituted or substituted C6-C10 aryl, substituted 5-7-membered heterocyclic ring, and —SO2R9;
• when both of R3 and R4 are hydrogen and R1 or R2 is an unsubstituted phenyl, then R6 and R7 are not hydrogen or methoxy (—OCH3);
• or when both of R3 and R4 are hydrogen and R1 or R2 is an unsubstituted phenyl and R6 and R7 are hydrogen or methoxy (—OCH3), then R5 is halogen;
• wherein the “substituted” refers to one or more hydrogen atoms on the group being substituted with a substituent selected from the group consisting of halogen, a C1-C6 alkyl unsubstituted or substituted by halogen or C3-C6 (preferably C1-C4) cycloalkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, C1-C4 linear or branched alkyl substituted amine group, hydroxy, cyano, nitro, oxygen atom (═O), hydroxy-C1-C6 alkyl, carboxyl, sulfydryl, C6-C10 aryl unsubstituted or substituted by 1 to 3 halogens or hydroxy groups, unsubstituted or halogenated 5-7 membered heterocyclic ring, unsubstituted or halogenated C2-C6 acyl, C1-C6 hydroxyalkyl, —NR9R10, —NCOR9R10, —SO2R9, —OSO2R9, —SO2NR9R10, —COOR9 and —OCOR9;
• n is 0 or 1;
• and when
• are both methyl, then R4 is selected from the group consisting of halogen, amine, hydroxy, a substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heterocyclic ring, substituted or unsubstituted C1-C6 alkylphenyl, substituted or unsubstituted C3-C12 cycloalkyl, substituted or unsubstituted C2-C10 acyl, substituted or unsubstituted C2-C10 ester group, amino, C1-C6 alkylamino, substituted or unsubstituted C1-C6 amide group, —SO2R9, —OSO2R9, and —OCOR9.