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US 11,952,364 B2Granted
TRK inhibitors useful as anticancer drugs
AssigneeTyligand Bioscience (Shanghai) Limited
InventorsBoyu Zhong, Tony Yantao Zhang, Yiju Cao, Guangming Chen
Life of this patent
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Abstract
A group of tropomyosin receptor kinase inhibitors including an amido-phenoxy-indazole structure fragment. These compounds show potent inhibitory effects on various oncogenic kinases, especially TRK, and thus can be used to treat tumors or cancers.
Claims24
A compound of formula I:
- wherein:
- R1 is C1-6 alkyl or C3-6 cycloalkyl, optionally substituted by one or more halogens, —ORa, C1-6 alkyl or amino;
- R5 is H, halogen, —ORa or optionally substituted C1-6 alkyl, and the substituent is selected from one or more halogen, —ORa, C1-6 alkyl or amino;
- or R1 and R5 together with the atoms to which they are attached form a cyclic structure of the following formula:
- where X is —CR7R8—, ═CR7—, —CR7R8—CR7R8— or —CR7═CR8—;
- R6, R7, R8 and R9 are independently selected from H, halogen, —ORa, optionally substituted C1-6 alkyl or C3-6 cycloalkyl, wherein the substituent is selected from one or more halogens, —ORa, C1-6 alkyl or amino;
- or
- R6 and R9 or R7 and R8 attached to the same carbon atom can form ═O or ═S together, or form a C3-6 cycloalkyl group together with the carbon atom to which they are attached;
- R2 is C1-6 alkyl optionally substituted by one or more halogens, C1-6 alkyl, C1-6 alkoxy or amino;
- C3-6 cycloalkyl or C3-6 heterocyclic group, optionally substituted by one or more halogens, —ORa, C1-6 alkyl or amino;
- nitro, cyano, acyl, halogen, mercapto, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkyl sulfinyl or carboxy;
- R3 and R4 are each independently selected from H, halogen, nitro, cyano, acyl or carboxy;
- Ra is selected from H or C1-6 alkyl;
- provided that R1 and R2 are not methyl at the same time,
- or isomers thereof, or their pharmaceutically acceptable salts or solvates.
12 more elements
A compound of formula III-a, isomers thereof or their pharmaceutically acceptable salts or solvates
- wherein
- R1 is C1-6 alkyl;
- R2 is —NRaRb or —ORb;
- R3 and R4 are each independently selected from H or halogen;
- Ra and Rb are each independently selected from H, C1-6 alkyl optionally substituted by one or more halogens, or C3-6 cycloalkyl optionally substituted by one or more halogens, or Ra and Rb together with the N to which they are attached form a 3-6 membered ring optionally substituted by one or more halogens.
2 more elements
A compound of formula III-b, isomers thereof or their pharmaceutically acceptable salts or solvates,
- wherein:
- R2 is —NRaRb or —ORb;
- X is —CR7R8—, ═CR7—, —CR7R8—CR7R8— or —CR7═CR8—;
- R6 and R9 are each independently H, halogen, —OH, C1-6 alkyl or C3-6 cycloalkyl;
- R7 and R8 are each independently H, halogen, —OH, C1-6 alkyl optionally substituted with one or more halogens or C3-6 cycloalkyl optionally substituted with one or more halogens, or R7 and R8 attached to the same carbon atom together form a C3-6 cycloalkyl;
- R3 and R4 are each independently selected from H or halogen;
- Ra and Rb are each independently selected from H, C1-6 alkyl optionally substituted by one or more halogens, or C3-6 cycloalkyl optionally substituted by one or more halogens, or Ra and Rb together with N to which they are attached form a 3-6 membered ring optionally substituted with one or more halogens.
4 more elements
A compound, isomers thereof or their pharmaceutically acceptable salts or solvates, selected from:
Dependencies are inferred from the claim text.