US 11,952,387 B2
Bicyclic heteroaromatic ring derivative
Masahiko Kinebuchi, Tochigi (JP); Takekazu Kondou, Tochigi (JP); Koji Ochiai, Tochigi (JP); and Yosuke Nishigaya, Tochigi (JP)
Assigned to KYORIN PHARMACEUTICAL CO., LTD, Tokyo (JP)
Appl. No. 15/734,655
Filed by KYORIN PHARMACEUTICAL CO., LTD., Tokyo (JP)
PCT Filed Aug. 20, 2019, PCT No. PCT/JP2019/032335
§ 371(c)(1), (2) Date Dec. 3, 2020,
PCT Pub. No. WO2020/040104, PCT Pub. Date Feb. 27, 2020.
Claims priority of application No. 2018-154411 (JP), filed on Aug. 21, 2018.
Prior Publication US 2022/0332730 A1, Oct. 20, 2022
Int. Cl. C07D 513/04 (2006.01); A61P 31/16 (2006.01)
CPC C07D 513/04 (2013.01) [A61P 31/16 (2018.01); C07B 2200/05 (2013.01)] 14 Claims
 
1. A compound represented by Formula (1):

OG Complex Work Unit Chemistry
wherein
X represents N or CH;
Q1 represents N or CH;
Q2 represents N or CR3;
L represents —SO2—, —SO2C(R8)2—, or —SO2NR8—;
R1 represents H; a C1-C6 alkyl group, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a haloC1-C6 alkyl group, a cyano group, a carboxy group, a C3-C10 cycloalkyl group, a 3- to 10-membered heterocycloalkyl group, a C3-C10 cycloalkyloxy group, a 3- to 10-membered heterocycloalkyloxy group, —C(O)R9, and —C(O)NR10R11; a C3-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of a haloC1-C6 alkyl group, a C1-C6 alkoxy group, a hydroxy group, and a cyano group; or a C2-C6 alkenyl group, wherein the alkenyl group is optionally substituted with one or more substituents selected from the group consisting of a halogen atom, a C1-C6 alkoxy group, a cyano group, a carboxy group, a C3-C10 cycloalkyl group, a 3- to 10-membered heterocycloalkyl group, a C3-C10 cycloalkyloxy group, a 3- to 10-membered heterocycloalkyloxy group, —C(O)R9, and —C(O)NR10R11;
R2 represents a C1-C6 alkyl group;
R3 represents H; a C1-C6 alkyl group, wherein the alkyl group is optionally substituted with one or more substituents selected from the group consisting of a halogen atom, a hydroxy group, a C1-C6 alkoxy group, a haloC1-C6 alkyl group, a cyano group, a C3-C10 cycloalkyl group, a 3- to 10-membered heterocycloalkyl group, a C3-C10 cycloalkyloxy group, a 3- to 10-membered heterocycloalkyloxy group, —C(O)R9, and —C(O)NR10R11; a hydroxy group; a C1-C6 alkoxy group; a haloC1-C6 alkyl group; a cyano group; a C3-C10 cycloalkyl group; a 3- to 10-membered heterocycloalkyl group; a C3-C10 cycloalkyloxy group; a 3- to 10-membered heterocycloalkyloxy group; —C(O)R9; —C(O)NR10R11; or a halogen atom;
R4 represents H, a halogen atom, a C1-C6 alkoxy group, a deuterated C1-C6 alkoxy group, a C1-C6 alkyl group, a haloC1-C6 alkyl group, a haloC1-C6 alkoxy group, a hydroxyC1-C6 alkyl group, a hydroxy group, a cyano group, —C(O)R9, —C(O)NR10R11, or NR10R11;
when Q2 is CR3, R3 and R4 may be joined together to form a ring;
G represents —R5—R6—R7; a hydroxyC1-C6 alkyl group, wherein the hydroxyC1-C6 alkyl group is optionally substituted with W1 and W2, wherein W1 and W2 are each independently selected from the group consisting of hydrogen, a C1-C6 alkyl group, a deuterated C1-C6 alkyl group, a haloC1-C6 alkyl group, and a hydroxyC1-C6 alkyl group, wherein W1 and W2 may be joined together to form a ring, and the ring formed by W1 and W2 is optionally substituted with one or more halogen atoms; a C3-C6 cycloalkyl group, wherein the C3-C6 cycloalkyl group is optionally substituted with W3 and W4, wherein W3 and W4 are each independently selected from the group consisting of hydrogen, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C1-C6 acyl group, a hydroxyC1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, —SO2R12, and an oxo group, and W3 and W4 may be joined together to form a ring; a C5-C8 bicycloalkyl group, wherein the C5-C8 bicycloalkyl group is optionally substituted with W3 and W4, wherein W3 and W4 are each independently selected from the group consisting of hydrogen, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C1-C6 acyl group, a hydroxyC1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, —SO2R12, and an oxo group, and W3 and W4 may be joined together to form a ring; a 3- to 10-membered heterocycloalkyl group, wherein the 3- to 10-membered heterocycloalkyl group is optionally substituted with W3 and W4, wherein W3 and W4 are each independently selected from the group consisting of hydrogen, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C1-C6 acyl group, a hydroxyC1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, —SO2R12, —C(O)N(R13)2, and an oxo group, and W3 and W4 may be joined together to form a ring; a C1-C6 alkyl group, wherein the C1-C6 alkyl group is optionally substituted with W5 and W6, wherein W5 and W6 are each independently selected from the group consisting of H, a cyano group, a hydroxyC1-C6 alkyl group, a C1-C6 alkyl group, a C1-C6 alkoxycarbonyl group, a carboxy group, and —C(O)N(R13)2, and W5 and W6 may be joined together to form a ring; a phenyl group, wherein the phenyl group is optionally substituted with one or more substituents selected from the group consisting of a halogen atom, a C1-C6 alkyl group, a hydroxyC1-C6 alkyl group, a C1-C6 acyl group, a carboxy group, a hydroxy group, a haloC1-C6 alkyl group, a cyano group, a C3-C10 cycloalkyl group, a 3-, to 10-membered heterocycloalkyl group, —NR10R11, —C(O)R9, —C(O)NR10R11, a C1-C6 alkoxycarbonyl group, —SO2R12, and a C1-C6 alkoxy group; or a heteroaryl group, wherein the heteroaryl group is optionally substituted with one or more substituents selected from the group consisting of a halogen atom, a C1-C6 alkyl group, a hydroxyC1-C6 alkyl group, a C1-C6 acyl group, a carboxy group, a hydroxy group, a haloC1-C6 alkyl group, a cyano group, a C3-C10 cycloalkyl group, a 3- to 10-membered heterocycloalkyl group, —NR10R11, —C(O)R9, —C(O)NR10R11, a C1-C6 alkoxycarbonyl group, —SO2R12, and a C1-C6 alkoxy group;
R5 represents a hydroxyC1-C6 alkylene group, wherein the hydroxyC1-C6 alkylene group is optionally substituted with W1 and W2, wherein W1 and W2 are each independently selected from the group consisting of H, a C1-C6 alkyl group, a deuterated C1-C6 alkyl group, a haloC1-C6 alkyl group, and a hydroxyC1-C6 alkyl group, and W1 and W2 may be joined together to form a ring, and the ring formed by W1 and W2 is optionally substituted with one or more halogen atoms; a C3-C6 cycloalkylene group, wherein the C3-C6 cycloalkylene group is optionally substituted with W3 and W4, wherein W3 and W4 are each independently selected from the group consisting of H, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C1-C6 acyl group, a hydroxyC1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, —SO2R12, and an oxo group, and W3 and W4 may be joined together to form a ring; a C5-C8 bicycloalkylene group, wherein the C5-C8 bicycloalkylene group is optionally substituted with W3 and W4, wherein W3 and W4 are each independently selected from the group consisting of H, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C1-C6 acyl group, a hydroxyC1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, —SO2R12, and an oxo group, and W3 and W4 may be joined together to form a ring; a 3- to 10-membered heterocycloalkylene group, wherein the 3- to 10-membered heterocycloalkylene group is optionally substituted with W3 and W4, wherein W3 and W4 are each independently selected from the group consisting of H, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C3-C10 cycloalkyl group, a C1-C6 acyl group, a hydroxyC1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, —SO2R12, —C(O)N(R13)2, and an oxo group, and W3 and W4 may be joined together to form a ring; a C1-C6 alkylene group, wherein the C1-C6 alkylene group is optionally substituted with W5 and W6, wherein W5 and W6 are each independently selected from the group consisting of H, a cyano group, a hydroxyC1-C6 alkyl group, a C1-C6 alkyl group, a C1-C6 alkoxycarbonyl group, a carboxy group, and —C(O)N(R13)2, and W5 and W6 may be joined together to form a ring; a phenylene group, wherein the phenylene group is optionally substituted with one or more substituents selected from the group consisting of a halogen atom, a C1-C6 alkyl group, a hydroxyC1-C6 alkyl group, a C1-C6 acyl group, a carboxy group, a hydroxy group, a haloC1-C6 alkyl group, a cyano group, a C3-C10 cycloalkyl group, a 3- to 10-membered heterocycloalkyl group, —NR10R11, —C(O)R9, —C(O)NR10R11, a C1-C6 alkoxycarbonyl group, —SO2R12, and a C1-C6 alkoxy group; or a heteroarylene group, wherein the heteroarylene group is optionally substituted with one or more substituents selected from the group consisting of a halogen atom, a C1-C6 alkyl group, a hydroxyC1-C6 alkyl group, a C1-C6 acyl group, a carboxy group, a hydroxy group, a haloC1-C6 alkyl group, a cyano group, a C3-C10 cycloalkyl group, a 3- to 10-membered heterocycloalkyl group, —NR10R11, —C(O)R9, —C(O)NR10R11, a C1-C6 alkoxycarbonyl group, —SO2R12, and a C1-C6 alkoxy group;
R6 represents a bond or a C3-C6 cycloalkylene group;
R7 represents H or a hydroxy group;
each R8 independently represents H or a C1-C6 alkyl group;
R9 represents H, a hydroxy group, a C1-C6 alkyl group, a C1-C6 alkoxy group, or a C3-C6 cycloalkoxy group;
R10 represents H or a C1-C6 alkyl group;
R11 represents H or a C1-C6 alkyl group;
R12 represents H or a C1-C6 alkyl group; and
each R13 independently represents H, a C1-C6 alkyl group, or a hydroxyC1-C6 alkyl group,
a pharmacologically acceptable salt of the compound, a hydrate of the compound or a hydrate of the salt.