Thiadiazole-substituted compound, pharmaceutical compositions thereof, and applications thereof
AssigneeShanghai Yingli Pharmaceutical Co., Ltd
InventorsZusheng XU, Yangtong LOU
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Abstract
Disclosed is a thiadiazole-substituted compound, pharmaceutical composition thereof and application thereof. The present disclosure provides a compound containing structure of a thiadiazole-substituted compound represented by formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, an isomer thereof or an isotopic compound thereof. The thiadiazole-substituted compound has strong inhibitory effect on PARG and and better pharmacokinetics, is expected to treat and/or prevent various PARG-related diseases.
Claims11
A thiadiazole-substituted compound represented by formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, an isomer thereof or an isotopic compound thereof:
- wherein, “” represents a single bond or a double bond;
- B is CF3 or CHF2;
- A1 is N or CRb1, Rb is hydrogen or halogen;
- and when B is CHF2, A1 is CRb1, Rb1 is halogen;
- A2 is N, C or CRc1;
- Rc1 is hydrogen, halogen, C1-6 alkyl or hydroxyl;
- A3 is CR23 or CHR23;
- Ra1 is cyano or C1-6 alkyl;
- R21 and R22 are independently hydrogen or C1-6 alkyl, and when R21 is hydrogen, R22 is C1-6 alkyl;
- R23 is hydrogen, halogen, hydroxyl, cyano, C1-6 alkyl, C1-6 alkyl substituted with one or more R23-1, C2-6 alkenyl, C2-6 alkynyl, —OC1-6 alkyl, —SC1-6 alkyl, —C(═O)R2a, —NR2b1R2b2, —C(═O)OR2c, —C(═O)NR2d1R2d2, C3-10 cycloalkyl, “4- to 12-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from O, S and N”, C6-20 aryl, “5- to 12-membered heteroaryl containing 1 to 4 heteroatoms independently selected from O, S and N”, C4-8 cycloalkenyl, or, “4- to 8-membered heterocycloalkenyl containing 1 to 3 heteroatoms independently selected from O, S and N”;
- R23-1 is independently halogen, cyano, C1-6 alkyl-O—, hydroxyl, —C(═O)R23a, —NR23b1R23b2, —C(═O)OR23e or —C(═O)NR23d1R23d2;
- R2a, R2b1, R2b2, R2c, R2d1, R2d2, R23a, R23b1, R23b2, R23c, R23d1 and R23d2 are independently hydrogen, C1-6 alkyl, or, C1-6 alkyl substituted with one or more halogen;
- or, R2b1 and R2b2, R2d1 and R2d2, R23b1 and R23b2, R23d1 and R23d2 independently together with the N to which they are attached form “3- to 8-membered heterocycle containing 1 to 3 heteroatoms, wherein, one heteroatom is N, other heteroatoms, if any, independently selected from O, S and N”, or “3- to 8-membered heterocycle containing 1 to 3 heteroatoms, wherein, one heteroatom is N, other heteroatoms, if any, independently selected from O, S and N” substituted with one or more R1-2-1;
- R1-2-1 is independently independently halogen, C1-6 alkyl, or, C1-6 alkyl substituted with one or more halogen.
Dependencies are inferred from the claim text.