Imidazopyridin-2-one derivatives
AssigneeDaiichi Sankyo Company, Limited
InventorsMasami Ohtsuka, Noriyasu Haginoya, Masanori Ichikawa, Hironori Matsunaga, Hironao Saito, Yoshihiro Shibata, Tomoyuki Tsunemi
Life of this patent
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Abstract
A compound represented by formula (I) having mTOR inhibitory activity or a pharmacologically acceptable salt thereof.
Claims45
A method for inhibiting a tumor treatable by inhibiting the mammalian target of rapamycin (mTOR), comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmacologically acceptable salt thereof to a subject in need thereof, the compound of formula (I) having the structure:
- wherein
- A is an 8- to 10-membered partially saturated or aromatic fused bicyclic nitrogen-containing heterocyclic group having 1 to 3 nitrogen atoms,
- A may have the same or different n R1s as substituents,
- R1 is a substituent selected from the group consisting of a hydroxy group, a halogen atom, a cyano group, an oxo group, a C1-4 alkyl group (wherein the C1-4 alkyl group may be substituted with one or two same or different C1-4 alkoxy groups or —NR7aR7bs), a C1-4 alkoxy group, a halogeno-C1-4 alkyl group, —NR7aR7b, —C(O)R8 and —C(O)NR9aR9b,
- n is any integer of 0 to 3,
- R7a, R7b, R9a and R9b are the same or different and are each a hydrogen atom or a C1-4 alkyl group (wherein the C1-4 alkyl group may be substituted with 1 or 2 hydroxy groups),
- R8 is a hydrogen atom, a hydroxy group, a C1-4 alkyl group or a C1-4 alkoxy group,
- B is a 3- to 7-membered saturated or partially saturated monocyclic hydrocarbon group and may contain 1 or 2 oxygen atoms, sulfur atoms, nitrogen atoms, sulfinyl groups and/or sulfonyl groups as ring constituents,
- B may have the same or different m R2s as substituents,
- R2 is a substituent present on a carbon atom or nitrogen atom forming B,
- R2 is a substituent selected from the group consisting of a hydroxy group, a halogen atom, a cyano group, an oxo group, a C1-4 alkyl group (wherein the C1-4 alkyl group may be substituted with 1 or 2 C1-4 alkoxy groups), a C1-4 alkoxy group, a halogeno-C1-4 alkyl group, a C1-4 alkylsulfonyl group, a C1-4 alkylcarbonyl group and —NR10aR10b when R2 is a substituent present on a carbon atom forming B, and R2 is a substituent selected from the group consisting of a hydroxy group, a C1-4 alkyl group (wherein the C1-4 alkyl group may be substituted with 1 or 2 C1-4 alkoxy groups), a C1-4 alkoxy group, a halogeno-C1-4 alkyl group, a C1-4 alkylsulfonyl group, a C1-4 alkylcarbonyl group and —NR10aR10b when R2 is a substituent present on a nitrogen atom forming B,
- R10a and R10b are the same or different and are each a hydrogen atom or a C1-4 alkyl group,
- m is any integer of 0 to 3,
- Q is a bond or a C1-4 alkylene group,
- R3 and R4 are the same or different and are each a hydrogen atom, a halogen atom, a C1-4 alkyl group, a halogeno-C1-4 alkyl group or a cyano group, and
- R5 and R6 are the same or different and are each a hydrogen atom, a halogen atom or a C1-4 alkyl group, or R5 and R6 together may form an oxo group or together with the carbon atom to which R5 and R6 are bonded may form a C3-8 cycloalkyl group.
A method for inhibiting the mammalian target of rapamycin (mTOR) is a subject, comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmacologically acceptable salt thereof to a subject in need thereof, the compound of formula (I) having the structure:
- wherein
- A is an 8- to 10-membered partially saturated or aromatic fused bicyclic nitrogen-containing heterocyclic group having 1 to 3 nitrogen atoms,
- A may have the same or different n R1s as substituents,
- R1 is a substituent selected from the group consisting of a hydroxy group, a halogen atom, a cyano group, an oxo group, a C1-4 alkyl group (wherein the C1-4 alkyl group may be substituted with one or two same or different C1-4 alkoxy groups or —NR7aR7bs), a C1-4 alkoxy group, a halogeno-C1-4 alkyl group, —NR7aR7b, —C(O)R8 and —C(O)NR9aR9b,
- n is any integer of 0 to 3,
- R7a, R7b, R9a and R9b are the same or different and are each a hydrogen atom or a C1-4 alkyl group (wherein the C1-4 alkyl group may be substituted with 1 or 2 hydroxy groups),
- R8 is a hydrogen atom, a hydroxy group, a C1-4 alkyl group or a C1-4 alkoxy group,
- B is a 3- to 7-membered saturated or partially saturated monocyclic hydrocarbon group and may contain 1 or 2 oxygen atoms, sulfur atoms, nitrogen atoms, sulfinyl groups and/or sulfonyl groups as ring constituents,
- B may have the same or different m R2s as substituents,
- R2 is a substituent present on a carbon atom or nitrogen atom forming B,
- R2 is a substituent selected from the group consisting of a hydroxy group, a halogen atom, a cyano group, an oxo group, a C1-4 alkyl group (wherein the C1-4 alkyl group may be substituted with 1 or 2 C1-4 alkoxy groups), a C1-4 alkoxy group, a halogeno-C1-4 alkyl group, a C1-4 alkylsulfonyl group, a C1-4 alkylcarbonyl group and —NR10aR10b when R2 is a substituent present on a carbon atom forming B, and R2 is a substituent selected from the group consisting of a hydroxy group, a C1-4 alkyl group (wherein the C1-4 alkyl group may be substituted with 1 or 2 C1-4 alkoxy groups), a C1-4 alkoxy group, a halogeno-C1-4 alkyl group, a C1-4 alkylsulfonyl group, a C1-4 alkylcarbonyl group and —NR10aR10b when R2 is a substituent present on a nitrogen atom forming B,
- R10a and R10b are the same or different and are each a hydrogen atom or a C1-4 alkyl group,
- m is any integer of 0 to 3,
- Q is a bond or a C1-4 alkylene group,
- R3 and R4 are the same or different and are each a hydrogen atom, a halogen atom, a C1-4 alkyl group, a halogeno-C1-4 alkyl group or a cyano group, and
- R5 and R6 are the same or different and are each a hydrogen atom, a halogen atom or a C1-4 alkyl group, or R5 and R6 together may form an oxo group or together with the carbon atom to which R5 and R6 are bonded may form a C3-8 cycloalkyl group.
Dependencies are inferred from the claim text.