JP-2022515158-A5 -

Dates

Publication Date

20221214

Application Date

20191220

Description

Example 33: Receptor Binding Profile Using the same receptor binding assay procedure as described in Example 7, the following additional data can be obtained for the following compounds: This application also includes the following aspects. [Aspect 1] Formula I, in its free form or salt form (e.g., pharmaceutically acceptable salt form), for example, in its isolated or purified free form or salt form (e.g., pharmaceutically acceptable salt form): [In the formula, R1 is H, C1-6 alkyl , -C(O)-O-C(Ra a )(R b )(R c ), -C(O)-O-CH2 - O-C(Ra a )(R b )(R c ), or -C(R 6 )(R 7 )-O-C(O)-R 8 ; R2 and R3 are independently selected from H, D, C1-6 alkyl (e.g., methyl), C1-6 alkoxy (e.g., methoxy), halo (e.g., F ) , cyano, or hydroxy; or R2 and R3 and the carbons to which they are bonded collectively form a -CH2CH2- group , or R2 and R3, and the carbon atoms to which they are bonded, are not present; L is a C1-6 alkylene (e.g., ethylene, propylene, or butylene), a C1-6 alkoxy ( e.g., propoxy or butoxy), a C2-3 alkoxy C1-3 alkylene (e.g., -CH2CH2OCH2- ) , a C1-6 alkylamino or N - C1-6 alkyl C1-6 alkylamino ( e.g. , propylamino or N - methylpropylamino), a C1-6 alkylthio ( e.g., -CH2CH2CH2S-), or a C1-6 alkylsulfonyl (e.g., -CH2CH2CH2S(O)2- ) , all of which may be substituted with one or more R4 moieties ; Each R4 is independently selected from C1-6 alkyl (e.g., methyl), C1-6 alkoxy (e.g., methoxy), halo (e.g., F), cyano, or hydroxy; Z is selected from aryl (e.g., phenyl) and heteroaryl (e.g., pyridyl, indazolyl, benzimidazolyl, benzoisoxazolyl), where the aryl or heteroaryl may be substituted with one or more R4 moieties ; R8 is -C(Ra a )(R b )(R c ), -O-C(Ra a )(R b )(R c ), or -N(R d )(Re ) ; Ra , Rb , and Rc are each independently selected from H and C1-24 alkyl groups ; Rd and Re are each independently selected from H and C1-24 alkyl groups ; R6 and R7 are each independently selected from H, C1-6 alkyl, carboxy, and C1-6 alkoxycarbonyl ; However, the L-Z portion is not 1-(4-(4-fluorophenyl)-4-oxobutyl), 1-(4-(4-fluorophenyl)-4-hydroxybutyl, or 1-(4-fluoro-1-phenoxy)propyl). The compound shown by [this symbol]. [Aspect 2] The compound according to embodiment 1 , wherein R1 is H. [Appearance 3] The compound according to embodiment 1, wherein R1 is a C1-6 alkyl group, for example , methyl . [Aspect 4] The compound according to embodiment 1, wherein R1 is -C(O)-O-C(Ra a)(R b)(R c), -C(O)-O-CH2-O-C(Ra a)(R b)(R c ) , or -C ( R 6 ) ( R 7 ) -O - C ( O ) -R 8 . [Aspect 5] The compound according to any one of embodiments 1 to 4 , wherein L is an unsubstituted C1-6 alkylene (e.g., ethylene, propylene, or butylene) or L is a C1-6 alkylene (e.g., ethylene, propylene, or butylene) substituted with one or more R4 moieties . [Pattern 6] The compound according to any one of embodiments 1 to 4 , wherein L is an unsubstituted C1-6 alkoxy (e.g., propoxy or butoxy) or L is a C1-6 alkoxy (e.g., propoxy or butoxy) substituted with one or more R4 moieties . [Appearance 7] A compound according to any one of embodiments 1 to 6, wherein R1 , R2 , and R3 are each H. [Patent 8] The compound according to any one of embodiments 1 to 7, wherein Z is an aryl (e.g., phenyl) which may be substituted with one or more R 4 moieties. [Aspect 9] The compound according to any one of embodiments 1 to 7, wherein Z is a phenyl compound substituted with one R 4 moiety selected from halo (e.g., fluoro, chloro, bromo, or iodine) and cyano (e.g., Z is 4-fluorophenyl, or 4-chlorophenyl, or 4-cyanophenyl). [Aspect 10] The compound according to any one of embodiments 1 to 7, wherein Z may be substituted with one or more R 4 moieties (e.g., pyridyl, indazolyl, benzimidazolyl, benzoisoxazolyl). [Personalization 11] The compound according to embodiment 10, wherein the heteroaryl is a monocyclic five-membered or six-membered heteroaryl (for example, pyridyl, pyrimidyl, pyrazinyl, thiophenyl, pyrrolyl, thiophenyl, furanyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl). [Aspect 12] The compound according to embodiment 10, wherein the heteroaryl is a bicyclic 9-membered or 10-membered heteroaryl (e.g., indolyl, isoindolyl, benzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, benzodioxolyl, 2-oxotetrahydroquinolinyl). [Aspect 13] The compound according to embodiment 10, wherein the heteroaryl is substituted with one R4 moiety selected from halo (e.g., fluoro, chloro, bromo, or iodine) and cyano (for example, the heteroaryl is 6-fluoro-3-indazolyl, 6-chloro-3-indazolyl, 6-fluoro-3-benzoisoxazolyl, or 5-chloro-3-benzoisoxazolyl). [Aspect 14] The compounds, each independently, exist in free form or pharmaceutically acceptable salt form. A compound according to any one of embodiments 1 to 13, selected from the group consisting of the above. [Phenomenon 15] The compounds, each independently, exist in free form or pharmaceutically acceptable salt form. A compound according