JPWO2021092115A5 - - Google Patents

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JPWO2021092115A5
JPWO2021092115A5 JP2022525714A JP2022525714A JPWO2021092115A5 JP WO2021092115 A5 JPWO2021092115 A5 JP WO2021092115A5 JP 2022525714 A JP2022525714 A JP 2022525714A JP 2022525714 A JP2022525714 A JP 2022525714A JP WO2021092115 A5 JPWO2021092115 A5 JP WO2021092115A5
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Priority claimed from PCT/US2020/059024 external-priority patent/WO2021092115A1/en
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式（Ｉ）の構造を有する化合物であって、
Figure 2021092115000001
 式中、
Ｒ１が、任意に置換された３～６員シクロアルキル、任意に置換された３～６員ヘテロシクリル、任意に置換された６員アリール、及び任意に置換された５～６員ヘテロアリールからなる群から選択され、
Ｒ２が、Ｈ、Ｃ１－６アルキル、ハロゲン、－ＮＨＲ２ａ、－ＯＲ２ａ、シクロプロピル、及び－ＣＮからなる群から選択され、Ｃ１－６アルキルが、ハロゲン、－ＮＨＲ２ａ、－ＯＲ２ａ、または５～６員ヘテロシクリルで任意に置換され、さらにＲ２ａが、Ｈ、Ｃ１－６アルキル、３～６員ヘテロシクリル、及びＣ１－６ハロアルキルからなる群から選択され、
Ｒ３が、Ｈ、Ｃ１－３アルキル、－ＯＲ３ａ、シクロプロピル、及び３～６員ヘテロシクリルからなる群から選択され、Ｃ１－３アルキル、シクロプロピル、及び３～６員ヘテロシクリルの各々が、Ｒ３ａで任意に置換され、さらにＲ３ａが、Ｃ１－３アルキル、ハロゲン、－ＯＨ、または－ＣＮからなる群から選択され、
Ｌ４が、結合、－Ｃ（Ｏ）－、－Ｃ（Ｏ）Ｏ－、－Ｃ（Ｏ）ＮＨ（ＣＨ２）ｏ－、－ＮＨ－、－Ｓ－、－Ｓ（Ｏ）２－、
Figure 2021092115000002
 －（ＣＨ２）ｐ－、及び－Ｏ－からなる群から選択され、ｏが、０、１、または２であり、ｐが、１～６の数であり、
Ｒ４が、Ｈ、Ｃ１－６アルキル、３～１４員シクロアルキル、３～１４員シクロアルケニル、３～１４員ヘテロシクリル、６～１０員アリール、及び５～１０員ヘテロアリールからなる群から選択され、各Ｃ１－６アルキル、３～１４員シクロアルキル、３～１４員シクロアルケニル、３～１４員ヘテロシクリル、６～１０員アリール、及び５～１０員ヘテロアリールが、Ｃ１－６アルキル、－Ｒ４ａ、－ＯＲ４ａ、－Ｏ－Ｃ１－６アルキル－Ｒ４ａ、＝Ｏ、ハロゲン、－Ｃ（Ｏ）Ｒ４ａ、－Ｃ（ＯＯ）Ｒ４ａ、－Ｃ（Ｏ）ＮＲ４ｂＲ４ｃ、－ＮＲ４ｂＣ（Ｏ）Ｒ４ｃ、－ＣＮ、＝ＮＲ４ａ、－ＮＲ４ｂＲ４ｃ、－ＳＯ２Ｒ４ａ、Ｒ４ａで任意に置換された３～６員シクロアルキル、Ｒ４ａで任意に置換された３～７員ヘテロシクリル、Ｒ４ａで任意に置換された６～１０員アリール、またはＲ４ａで任意に置換された５～１０員ヘテロアリールで任意に置換され、
Ｒ４ａが、Ｈ、Ｃ１－６アルキル、Ｃ１－６ハロアルキル、－Ｃ（Ｏ）Ｒ４ｂ、－Ｃ（Ｏ）ＮＲ４ｂＲ４ｃ、＝Ｏ、３～６員シクロアルキル、－ＯＲ４ｂで任意に置換された６～１０員アリール、－ＣＮ、＝Ｎ－３～６員シクロアルキル、３～７員ヘテロシクリル、－（ＣＨ２）ｒＯＣＨ３、または－（ＣＨ２）ｒＯＨであり、ｒが、１、２、または３であり、
各Ｒ４ｂが、独立して、Ｈ、Ｃ１－６アルキルであり、
各Ｒ４ｃが、独立して、ＨまたはＣ１－６アルキルである、前記化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 A compound having the structure of formula (I),
Figure 2021092115000001
 During the ceremony,
R 1 consists of an optionally substituted 3- to 6-membered cycloalkyl, an optionally substituted 3- to 6-membered heterocyclyl, an optionally substituted 6-membered aryl, and an optionally substituted 5- to 6-membered heteroaryl selected from the group,
R 2 is selected from the group consisting of H, C 1-6 alkyl, halogen, -NHR 2a , -OR 2a , cyclopropyl, and -CN, and C 1-6 alkyl is halogen, -NHR 2a , -OR 2a , or optionally substituted with 5-6 membered heterocyclyl, and further R 2a is selected from the group consisting of H, C 1-6 alkyl, 3-6 membered heterocyclyl, and C 1-6 haloalkyl;
R 3 is selected from the group consisting of H, C 1-3 alkyl, -OR 3a , cyclopropyl, and 3-6 membered heterocyclyl, and each of C 1-3 alkyl, cyclopropyl, and 3-6 membered heterocyclyl is , R 3a is selected from the group consisting of C 1-3 alkyl, halogen, -OH, or -CN;
L 4 is a bond, -C(O)-, -C(O)O-, -C(O)NH(CH 2 ) o -, -NH-, -S-, -S(O) 2 -,
Figure 2021092115000002
 selected from the group consisting of -(CH 2 ) p - and -O-, where o is 0, 1, or 2, and p is a number from 1 to 6;
R 4 is selected from the group consisting of H, C 1-6 alkyl, 3- to 14-membered cycloalkyl, 3- to 14-membered cycloalkenyl, 3- to 14-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 10-membered heteroaryl and each C 1-6 alkyl, 3- to 14-membered cycloalkyl, 3- to 14-membered cycloalkenyl, 3- to 14-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 10-membered heteroaryl is C 1-6 alkyl, -R 4a , -OR 4a , -O-C 1-6alkyl -R 4a , =O, halogen, -C(O)R 4a , -C(OO)R 4a , -C(O)NR 4b R 4c , -NR 4b C(O)R 4c , -CN, =NR 4a , -NR 4b R 4c , -SO 2 R 4a , 3- to 6-membered cycloalkyl optionally substituted with R 4a , optionally substituted with R 4a optionally substituted with a substituted 3- to 7-membered heterocyclyl, a 6- to 10-membered aryl optionally substituted with R 4a , or a 5- to 10-membered heteroaryl optionally substituted with R 4a ;
R 4a is H, C 1-6 alkyl, C 1-6 haloalkyl, -C(O)R 4b , -C(O)NR 4b R 4c , =O, 3- to 6-membered cycloalkyl, -OR 4b optionally substituted 6- to 10-membered aryl, -CN, =N-3- to 6-membered cycloalkyl, 3- to 7-membered heterocyclyl, -(CH 2 ) r OCH 3, or -(CH 2 ) r OH, r is 1, 2, or 3;
each R 4b is independently H, C 1-6 alkyl;
Said compound, or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof, wherein each R 4c is independently H or C 1-6 alkyl. Ｒ１が、任意に置換された６員アリールである、請求項１に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof, wherein R 1 is an optionally substituted 6-membered aryl. Ｒ１が、任意に置換された５～６員ヘテロアリールである、請求項１に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 The compound according to claim 1, or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof, wherein R 1 is an optionally substituted 5- to 6-membered heteroaryl. body. 式（ＩＩ）の構造を有し、
Figure 2021092115000003
 式中、Ｒ２、Ｒ３、Ｌ４、及びＲ４が、請求項１に定義されるとおりであり、
Ｒ５、Ｒ６、Ｒ７、Ｒ８、及びＲ９が、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、－ＯＨ、ハロゲン、－ＮＯ２、－ＣＮ、－ＮＲ１１Ｒ１２、－ＳＲ１０、－Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－Ｓ（Ｏ）２Ｒ１０、－ＮＲ１０Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）２Ｒ１１、－Ｓ（Ｏ）ＮＲ１１Ｒ１２、－Ｓ（Ｏ）Ｒ１０、－ＮＲ１０Ｓ（Ｏ）ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）Ｒ１１、－Ｃ（Ｏ）Ｒ１０、－ＣＯ２Ｒ１０、６～１０員アリール、及び５～１０員ヘテロアリールからなる群から選択され、各Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、６～１０員アリール、及び５～１０員ヘテロアリールが、－ＯＨ、－Ｒ１０で任意に置換されたＣ１－６アルキル、ハロゲン、－ＮＯ２、オキソ、－ＣＮ、－Ｒ１０、－ＯＲ１０、－ＮＲ１１Ｒ１２、－ＳＲ１０、－Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－Ｓ（Ｏ）２Ｒ１０、－ＮＲ１０Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）２Ｒ１１、－Ｓ（Ｏ）ＮＲ１１Ｒ１２、－Ｓ（Ｏ）Ｒ１０、－ＮＲ１０Ｓ（Ｏ）ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）Ｒ１１、３～８員シクロアルキル、Ｒ１０で任意に置換された３～１４員ヘテロシクリル、６～１０員アリール、もしくは５～１０員ヘテロアリールで任意に置換されているか、または任意の２つの隣接するＲ５、Ｒ６、Ｒ７、Ｒ８、及びＲ９が、任意に置換された３～１４員縮合環を形成し、
Ｒ１０、Ｒ１１、及びＲ１２が、各出現時に、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、－ＯＲ１３、－ＳＲ１３、ハロゲン、－ＮＲ１３Ｒ１４、－ＮＯ２、及び－ＣＮから選択され、
Ｒ１３及びＲ１４が、各出現時に、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、及び３～１４員ヘテロシクリルから選択され、各Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、及び３～１４員ヘテロシクリルが、独立して、－ＯＨ、－ＳＨ、－ＮＨ２、－ＮＯ２、または－ＣＮで任意に置換されている、請求項１に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 has the structure of formula (II),
Figure 2021092115000003
 wherein R 2 , R 3 , L 4 and R 4 are as defined in claim 1;
R 5 , R 6 , R 7 , R 8 , and R 9 are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3-8 membered cycloalkyl, 3-14 membered heterocyclyl, -OH, halogen, -NO 2 , -CN, -NR 11 R 12 , -SR 10 , -S(O) 2 NR 11 R 12 , -S(O ) 2 R 10 , -NR 10 S(O) 2 NR 11 R 12 , -NR 10 S(O) 2 R 11 , -S(O)NR 11 R 12 , -S(O)R 10 , -NR 10 From the group consisting of S(O)NR 11 R 12 , -NR 10 S(O)R 11 , -C(O)R 10 , -CO 2 R 10 , 6-10 membered aryl, and 5-10 membered heteroaryl selected, each C 1-6 alkyl, C 2-6 alkenyl, 4-8 membered cycloalkenyl, C 2-6 alkynyl, 3-8 membered cycloalkyl, 3-14 membered heterocyclyl, 6-10 membered aryl, and 5 ~10-membered heteroaryl is -OH, C 1-6 alkyl optionally substituted with -R 10 , halogen, -NO 2 , oxo, -CN, -R 10 , -OR 10 , -NR 11 R 12 , -SR 10 , -S(O) 2 NR 11 R 12 , -S(O) 2 R 10 , -NR 10 S(O) 2 NR 11 R 12 , -NR 10 S(O) 2 R 11 , -S (O)NR 11 R 12 , -S(O)R 10 , -NR 10 S(O)NR 11 R 12 , -NR 10 S(O)R 11 , 3- to 8-membered cycloalkyl, R 10 optionally optionally substituted with substituted 3- to 14-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or any two adjacent R 5 , R 6 , R 7 , R 8 , and R 9 forms an optionally substituted 3- to 14-membered fused ring,
R 10 , R 11 , and R 12 at each occurrence are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to selected from 8-membered cycloalkyl, 3-14-membered heterocyclyl, -OR 13 , -SR 13 , halogen, -NR 13 R 14 , -NO 2 , and -CN,
At each occurrence, R 13 and R 14 are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to 8-membered cycloalkyl , and 3- to 14-membered heterocyclyl, each C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to 8-membered cycloalkyl, and 3- to 14-membered heterocyclyl is independently optionally substituted with -OH, -SH, -NH2 , -NO2 , or -CN, or a pharmaceutically acceptable salt thereof, a solvent. hydrate, isomer, prodrug, or tautomer. 式（ＩＩＩ）の構造を有し、
Figure 2021092115000004
 式中、Ｒ２、Ｒ３、Ｌ４、及びＲ４が、請求項１に定義されるとおりであり、
Ｒ５、Ｒ６、Ｒ７、Ｒ８、及びＲ９が、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、－ＯＨ、ハロゲン、－ＮＯ２、－ＣＮ、－ＮＲ１１Ｒ１２、－ＳＲ１０、－Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－Ｓ（Ｏ）２Ｒ１０、－ＮＲ１０Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）２Ｒ１１、－Ｓ（Ｏ）ＮＲ１１Ｒ１２、－Ｓ（Ｏ）Ｒ１０、－ＮＲ１０Ｓ（Ｏ）ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）Ｒ１１、－Ｃ（Ｏ）Ｒ１０、－ＣＯ２Ｒ１０、６～１０員アリール、及び５～１０員ヘテロアリールからなる群から選択され、各Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、６～１０員アリール、及び５～１０員ヘテロアリールが、－ＯＨ、－Ｒ１０で任意に置換されたＣ１－６アルキル、ハロゲン、－ＮＯ２、オキソ、－ＣＮ、－Ｒ１０、－ＯＲ１０、－ＮＲ１１Ｒ１２、－ＳＲ１０、－Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－Ｓ（Ｏ）２Ｒ１０、－ＮＲ１０Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）２Ｒ１１、－Ｓ（Ｏ）ＮＲ１１Ｒ１２、－Ｓ（Ｏ）Ｒ１０、－ＮＲ１０Ｓ（Ｏ）ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）Ｒ１１、３～８員シクロアルキル、Ｒ１０で任意に置換された３～１４員ヘテロシクリル、６～１０員アリール、もしくは５～１０員ヘテロアリールで任意に置換されているか、または任意の２つの隣接するＲ５、Ｒ６、Ｒ７、Ｒ８、及びＲ９が、任意に置換された３～１４員縮合環を形成し、
Ｒ１０、Ｒ１１、及びＲ１２が、各出現時に、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、－ＯＲ１３、－ＳＲ１３、ハロゲン、－ＮＲ１３Ｒ１４、－ＮＯ２、及び－ＣＮから選択され、
Ｒ１３及びＲ１４が、各出現時に、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、及び３～１４員ヘテロシクリルから選択され、各Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、及び３～１４員ヘテロシクリルが、独立して、－ＯＨ、－ＳＨ、－ＮＨ２、－ＮＯ２、または－ＣＮで任意に置換されている、請求項１に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 has the structure of formula (III),
Figure 2021092115000004
 wherein R 2 , R 3 , L 4 and R 4 are as defined in claim 1;
R 5 , R 6 , R 7 , R 8 , and R 9 are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3-8 membered cycloalkyl, 3-14 membered heterocyclyl, -OH, halogen, -NO 2 , -CN, -NR 11 R 12 , -SR 10 , -S(O) 2 NR 11 R 12 , -S(O ) 2 R 10 , -NR 10 S(O) 2 NR 11 R 12 , -NR 10 S(O) 2 R 11 , -S(O)NR 11 R 12 , -S(O)R 10 , -NR 10 From the group consisting of S(O)NR 11 R 12 , -NR 10 S(O)R 11 , -C(O)R 10 , -CO 2 R 10 , 6-10 membered aryl, and 5-10 membered heteroaryl selected, each C 1-6 alkyl, C 2-6 alkenyl, 4-8 membered cycloalkenyl, C 2-6 alkynyl, 3-8 membered cycloalkyl, 3-14 membered heterocyclyl, 6-10 membered aryl, and 5 ~10-membered heteroaryl is -OH, C 1-6 alkyl optionally substituted with -R 10 , halogen, -NO 2 , oxo, -CN, -R 10 , -OR 10 , -NR 11 R 12 , -SR 10 , -S(O) 2 NR 11 R 12 , -S(O) 2 R 10 , -NR 10 S(O) 2 NR 11 R 12 , -NR 10 S(O) 2 R 11 , -S (O)NR 11 R 12 , -S(O)R 10 , -NR 10 S(O)NR 11 R 12 , -NR 10 S(O)R 11 , 3- to 8-membered cycloalkyl, R 10 optionally optionally substituted with substituted 3- to 14-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or any two adjacent R 5 , R 6 , R 7 , R 8 , and R 9 forms an optionally substituted 3- to 14-membered fused ring,
R 10 , R 11 , and R 12 at each occurrence are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to selected from 8-membered cycloalkyl, 3-14-membered heterocyclyl, -OR 13 , -SR 13 , halogen, -NR 13 R 14 , -NO 2 , and -CN,
At each occurrence, R 13 and R 14 are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to 8-membered cycloalkyl , and 3- to 14-membered heterocyclyl, each C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to 8-membered cycloalkyl, and 3- to 14-membered heterocyclyl is independently optionally substituted with -OH, -SH, -NH2 , -NO2 , or -CN, or a pharmaceutically acceptable salt thereof, a solvent. hydrate, isomer, prodrug, or tautomer. 式（ＩＶ－ａ）、（ＩＶ－ｂ）、または（ＩＶ－ｃ）の構造を有し、
Figure 2021092115000005
 式中、Ｒ２、Ｒ３、Ｌ４、及びＲ４が、請求項１に定義されるとおりであり、
Ｒ５、Ｒ６、Ｒ７、Ｒ８、及びＲ９が、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、－ＯＨ、ハロゲン、－ＮＯ２、－ＣＮ、－ＮＲ１１Ｒ１２、－ＳＲ１０、－Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－Ｓ（Ｏ）２Ｒ１０、－ＮＲ１０Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）２Ｒ１１、－Ｓ（Ｏ）ＮＲ１１Ｒ１２、－Ｓ（Ｏ）Ｒ１０、－ＮＲ１０Ｓ（Ｏ）ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）Ｒ１１、－Ｃ（Ｏ）Ｒ１０、－ＣＯ２Ｒ１０、６～１０員アリール、及び５～１０員ヘテロアリールからなる群から選択され、各Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、６～１０員アリール、及び５～１０員ヘテロアリールが、－ＯＨ、－Ｒ１０で任意に置換されたＣ１－６アルキル、ハロゲン、－ＮＯ２、オキソ、－ＣＮ、－Ｒ１０、－ＯＲ１０、－ＮＲ１１Ｒ１２、－ＳＲ１０、－Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－Ｓ（Ｏ）２Ｒ１０、－ＮＲ１０Ｓ（Ｏ）２ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）２Ｒ１１、－Ｓ（Ｏ）ＮＲ１１Ｒ１２、－Ｓ（Ｏ）Ｒ１０、－ＮＲ１０Ｓ（Ｏ）ＮＲ１１Ｒ１２、－ＮＲ１０Ｓ（Ｏ）Ｒ１１、３～８員シクロアルキル、Ｒ１０で任意に置換された３～１４員ヘテロシクリル、６～１０員アリール、もしくは５～１０員ヘテロアリールで任意に置換されているか、または任意の２つの隣接するＲ５、Ｒ６、Ｒ７、Ｒ８、及びＲ９が、任意に置換された３～１４員縮合環を形成し、
Ｒ１０、Ｒ１１、及びＲ１２が、各出現時に、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、３～１４員ヘテロシクリル、－ＯＲ１３、－ＳＲ１３、ハロゲン、－ＮＲ１３Ｒ１４、－ＮＯ２、及び－ＣＮから選択され、
Ｒ１３及びＲ１４が、各出現時に、独立して、Ｈ、Ｄ、Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、及び３～１４員ヘテロシクリルから選択され、各Ｃ１－６アルキル、Ｃ２－６アルケニル、４～８員シクロアルケニル、Ｃ２－６アルキニル、３～８員シクロアルキル、及び３～１４員ヘテロシクリルが、独立して、－ＯＨ、－ＳＨ、－ＮＨ２、－ＮＯ２、または－ＣＮで任意に置換されている、請求項１に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 having the structure of formula (IV-a), (IV-b), or (IV-c),
Figure 2021092115000005
 wherein R 2 , R 3 , L 4 and R 4 are as defined in claim 1;
R 5 , R 6 , R 7 , R 8 , and R 9 are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3-8 membered cycloalkyl, 3-14 membered heterocyclyl, -OH, halogen, -NO 2 , -CN, -NR 11 R 12 , -SR 10 , -S(O) 2 NR 11 R 12 , -S(O ) 2 R 10 , -NR 10 S(O) 2 NR 11 R 12 , -NR 10 S(O) 2 R 11 , -S(O)NR 11 R 12 , -S(O)R 10 , -NR 10 From the group consisting of S(O)NR 11 R 12 , -NR 10 S(O)R 11 , -C(O)R 10 , -CO 2 R 10 , 6-10 membered aryl, and 5-10 membered heteroaryl selected, each C 1-6 alkyl, C 2-6 alkenyl, 4-8 membered cycloalkenyl, C 2-6 alkynyl, 3-8 membered cycloalkyl, 3-14 membered heterocyclyl, 6-10 membered aryl, and 5 ~10-membered heteroaryl is -OH, C 1-6 alkyl optionally substituted with -R 10 , halogen, -NO 2 , oxo, -CN, -R 10 , -OR 10 , -NR 11 R 12 , -SR 10 , -S(O) 2 NR 11 R 12 , -S(O) 2 R 10 , -NR 10 S(O) 2 NR 11 R 12 , -NR 10 S(O) 2 R 11 , -S (O)NR 11 R 12 , -S(O)R 10 , -NR 10 S(O)NR 11 R 12 , -NR 10 S(O)R 11 , 3- to 8-membered cycloalkyl, R 10 optionally optionally substituted with substituted 3- to 14-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or any two adjacent R 5 , R 6 , R 7 , R 8 , and R 9 forms an optionally substituted 3- to 14-membered fused ring,
R 10 , R 11 , and R 12 at each occurrence are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to selected from 8-membered cycloalkyl, 3-14-membered heterocyclyl, -OR 13 , -SR 13 , halogen, -NR 13 R 14 , -NO 2 , and -CN,
At each occurrence, R 13 and R 14 are independently H, D, C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to 8-membered cycloalkyl , and 3- to 14-membered heterocyclyl, each C 1-6 alkyl, C 2-6 alkenyl, 4- to 8-membered cycloalkenyl, C 2-6 alkynyl, 3- to 8-membered cycloalkyl, and 3- to 14-membered heterocyclyl is independently optionally substituted with -OH, -SH, -NH2 , -NO2 , or -CN, or a pharmaceutically acceptable salt thereof, a solvent. hydrate, isomer, prodrug, or tautomer. 任意の２つの隣接するＲ５、Ｒ６、Ｒ７、Ｒ８、及びＲ９が、３～１４員縮合環を形成し、前記縮合環が、ハロゲンで置換されている、請求項４～６のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 Claims 4 to 6, wherein any two adjacent R 5 , R 6 , R 7 , R 8 , and R 9 form a 3- to 14-membered fused ring, and the fused ring is substituted with halogen. or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof. Ｒ２が、Ｈである、請求項１～７のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 8. A compound according to any one of claims 1 to 7 , wherein R 2 is H, or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof. Ｒ２が、Ｃ１－６アルキルである、請求項１～７のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 The compound according to any one of claims 1 to 7 , or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof, wherein R 2 is C 1-6 alkyl. Gender body. Ｒ３が、Ｃ１－３アルキルである、請求項１～９のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 The compound according to any one of claims 1 to 9 , or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof, wherein R 3 is C 1-3 alkyl. Gender body. Ｒ３が、Ｈ、シクロプロピル、または３～６員ヘテロシクリルである、請求項１～９のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 The compound according to any one of claims 1 to 9 , or a pharmaceutically acceptable salt, solvate, isomer thereof, wherein R 3 is H, cyclopropyl, or 3- to 6-membered heterocyclyl, Prodrugs or tautomers. Ｌ４が、結合、－Ｃ（Ｏ）－、－Ｃ（Ｏ）Ｏ－、－Ｃ（Ｏ）ＮＨ（ＣＨ２）ｏ－、－ＮＨ－、－Ｓ－、－Ｓ（Ｏ）２－、
Figure 2021092115000006
 －（ＣＨ２）ｐ－、及び－Ｏ－からなる群から選択され、ｏが、０、１、または２であり、ｐが、１～６の数である、請求項１～１１のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 L 4 is a bond, -C(O)-, -C(O)O-, -C(O)NH(CH 2 ) o -, -NH-, -S-, -S(O) 2 -,
Figure 2021092115000006
 -(CH 2 ) p -, and -O-, wherein o is 0, 1, or 2, and p is a number from 1 to 6 . A compound according to item 1, or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof. Ｌ４が、結合である、請求項１～１１のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 A compound according to any one of claims 1 to 11 , or a pharmaceutically acceptable salt, solvate, isomer, prodrug, or tautomer thereof, wherein L 4 is a bond. Ｒ４が、Ｈ、Ｃ１－６アルキル、３～１４員シクロアルキル、３～１４員シクロアルケニル、３～１４員ヘテロシクリル、６～１０員アリール、及び５～１０員ヘテロアリールからなる群から選択され、各Ｃ１－６アルキル、３～１４員シクロアルキル、３～１４員シクロアルケニル、３～１４員ヘテロシクリル、６～１０員アリール、及び５～１０員ヘテロアリールが、Ｃ１－６アルキル－ＯＲ４ａ、＝Ｏ、ハロゲン、－Ｃ（Ｏ）Ｒ４ａ、－Ｃ（ＯＯ）Ｒ４ａ、－Ｃ（Ｏ）ＮＲ４ｂＲ４ｃ、－ＣＮ、－ＮＲ４ｂＲ４ｃ、３～６員シクロアルキル、３～７員ヘテロシクリル、６～１０員アリール、または５～１０員ヘテロアリールで任意に置換されている、請求項１～１３のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、異性体、プロドラッグ、もしくは互変異性体。 R 4 is selected from the group consisting of H, C 1-6 alkyl, 3- to 14-membered cycloalkyl, 3- to 14-membered cycloalkenyl, 3- to 14-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 10-membered heteroaryl and each C 1-6 alkyl, 3- to 14-membered cycloalkyl, 3- to 14-membered cycloalkenyl, 3- to 14-membered heterocyclyl, 6- to 10-membered aryl, and 5- to 10-membered heteroaryl is C 1-6 alkyl- OR 4a , =O, halogen, -C(O)R 4a , -C(OO)R 4a , -C(O)NR 4b R 4c , -CN, -NR 4b R 4c , 3- to 6-membered cycloalkyl, A compound according to any one of claims 1 to 13 , or a pharmaceutically acceptable compound thereof, optionally substituted with a 3- to 7-membered heterocyclyl, a 6- to 10-membered aryl, or a 5- to 10-membered heteroaryl. Salts, solvates, isomers, prodrugs, or tautomers. コレクション１、コレクション２、コレクション３、コレクション４、もしくはコレクション５の化合物からなる群から選択される、請求項１に記載の化合物、またはその医薬的に許容される塩、溶媒和物、水和物、互変異性体、もしくは異性体。 A compound according to claim 1 , or a pharmaceutically acceptable salt, solvate, or hydrate thereof, selected from the group consisting of compounds of Collection 1, Collection 2, Collection 3, Collection 4, or Collection 5. , tautomer, or isomer. 表Ａの化合物からなる群から選択される、請求項１に記載の化合物、またはその医薬的に許容される塩、溶媒和物、水和物、互変異性体、もしくは異性体。 2. A compound according to claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or isomer thereof, selected from the group consisting of the compounds of Table A. 請求項１～１６のいずれか１項に記載の化合物、またはその医薬的に許容される塩、溶媒和物、水和物、互変異性体、もしくは異性体と、医薬的に許容される担体と、を含む、医薬組成物。 A compound according to any one of claims 1 to 16 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or isomer thereof, and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising. がんの治療または予防を必要とする対象においてそれを行う方法において使用するための、請求項１７に記載の医薬組成物。 18. A pharmaceutical composition according to claim 17 for use in a method of treating or preventing cancer in a subject in need thereof.
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