A class of polycyclic compounds inhibiting rna helicase dhx33 and the application thereof

A compound having the structure of formula II or a pharmaceutically acceptable form thereof:

• wherein
• X1 is N or CR1, X2 is N or CR2, X3 is N or CR3, X4 is N or CR4, provided that at least one of X1, X2, X3 and X4 is N;
• R1, R2, R3 and R4 are each independently hydrogen, halogen, amino, nitro, hydroxyl, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, —NH(C1-4 alkyl), —N(C1-4 alkyl)2, C1-4 hydroxyalkyl, —O—(C1-4 alkylene)-O—(C1-4 alkyl), —C(═O)—NH—(C1-4 alkyl), —C(═O)—NH—(C1-4 alkylene)-N(C1-4 alkyl)2, or —C(═O)—O—(C1-4 alkyl);
• X5 is N or CR5, X6 is NR6 or CR7R8, provided that at least one of X5 and X6 is N or a nitrogen-containing group;
• R5 is hydrogen or C1-4 alkyl;
• R6 is hydrogen, C1-6 alkyl, or —(C1-4 alkylene)-O—(C1-4 alkyl);
• R7 and R8 are each independently hydrogen or C1-4 alkyl;
• R10 is hydrogen, C1-6 alkyl, or C2-4 alkenyl, alternatively, R10 and X6 together with the atoms to which they are attached form a 5-7 membered ring;
• R9 is hydrogen, cyano, halogen, C1-6 alkyl, or C2-4 alkenyl;
• ring A is a pyrrole ring, a pyrazole ring, an imidazole ring, a thiazole ring or an oxazole ring, alternatively, ring A and R9 together with the atoms to which they are attached form an indole ring, an isoindole ring, a benzimidazole ring, a benzothiazole ring, or a benzoxazole ring;
• ring A is optionally substituted with one or more R11;
• each R11 is independently halogen, C1-4 alkyl, or C1-4 haloalkyl;
• ring B is a pyrrole ring, a pyrazole ring, an imidazole ring, a triazole ring, a furan ring, an oxazole ring, an isoxazole ring, an oxadiazole ring, a thiophene ring, a thiazole ring, an isothiazole ring, a thiadiazole ring, a benzene ring, or a pyridine ring;
• ring B is optionally substituted with one or more R12;
• each R12 is independently halogen, cyano, amino, nitro, hydroxyl, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C3-6 cycloalkyl, —C(═O)—O—(C1-4 alkyl), phenyl, benzyl, pyridyl, —C(═O)—NH2, or —NH—C(═O)—(C1-4 alkyl), said phenyl, benzyl and pyridyl are optionally substituted with one or more substituents selected from hydrogen, halogen, cyano, amino, hydroxyl, C1-4 alkyl and C1-4 alkoxy;
• and
• said pharmaceutically acceptable form is selected from a pharmaceutically acceptable salt, an ester, a stereoisomer, a tautomer, a solvate, a N-oxide, an isotopically labeled form, a metabolite and a prodrug.

A compound having the structure of formula V or a pharmaceutically acceptable form thereof:

• wherein
• X1 is N or CR1, X2 is N or CR2, X3 is N or CR3, X4 is N or CR4;
• R1, R2, R3 and R4 are each independently hydrogen, halogen, amino, nitro, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, —NH(C1-6 alkyl), —N(C1-4 alkyl)2, C1-6 hydroxyalkyl, —O—(C1-6 alkylene)-O—(C1-6 alkyl), —C(═O)—NH—(C1-6 alkyl), —C(═O)—NH—(C1-6 alkylene)-N(C1-6 alkyl)2, or —C(═O)—O—(C1-6 alkyl);
• R5 is hydrogen, halogen, or C1-6 alkyl;
• ring A is a 5-10 membered heteroaryl or a 3-8 membered heterocyclyl, ring A is optionally substituted with one or more R6;
• each R6 is independently halogen, C1-6 alkyl, or C1-6 haloalkyl;
• L is O, S, or CR7R8;
• R7 and R8 are each independently hydrogen, halogen, or C1-6 alkyl;
• ring B is C6-10 aryl, a 5-12 membered heteroaryl, or a 3-8 membered heterocyclyl, ring B is optionally substituted with one or more R9;
• each R9 is independently halogen, cyano, amino, nitro, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 cycloalkyl, —C(═O)—O—(C1-6 alkyl), phenyl, benzyl, pyridyl, —C(═O)—NH2, or —NH—C(═O)—(C1 alkyl), said phenyl, benzyl and pyridyl are optionally substituted with one or more substituents selected from hydrogen, halogen, cyano, amino, hydroxyl, C1 alkyl and C1 alkoxy;
• and
• said pharmaceutically acceptable form is selected from a pharmaceutically acceptable salt, an ester, a stereoisomer, a tautomer, a solvate, a N-oxide, an isotopically labeled form, a metabolite and a prodrug.