US 12,263,167 B2
Optically active azabicyclo ring derivative
Seiji Kamioka, Osaka (JP); Hitoshi Ban, Osaka (JP); Naoaki Shimada, Osaka (JP); Wataru Hirose, Osaka (JP); Akihiko Arakawa, Odawara (JP); Kazuto Yamazaki, Ikoma (JP); and Kenjiro Hira, Osaka (JP)
Assigned to Sumitomo Pharma Co., Ltd., Osaka (JP)
Filed by Sumitomo Pharma Co., Ltd., Osaka (JP)
Filed on Jan. 12, 2024, as Appl. No. 18/412,308.
Application 18/412,308 is a continuation of application No. 17/750,721, filed on May 23, 2022, granted, now 11,911,381.
Application 17/750,721 is a continuation of application No. 16/629,739, granted, now 11,369,605, issued on Jun. 28, 2022, previously published as PCT/JP2019/033234, filed on Aug. 26, 2019.
Claims priority of application No. 2018-158315 (JP), filed on Aug. 27, 2018.
Prior Publication US 2024/0148727 A1, May 9, 2024
Int. Cl. A61K 31/506 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07D 519/00 (2006.01)
CPC A61K 31/506 (2013.01) [A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 519/00 (2013.01)] 19 Claims
 
1. A compound of formula (Ib):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
p is 1 or 2;
R1, R2, R3, and R4 are each independently a hydrogen atom, a halogen atom, —OR7, or M-Q; or R1 and R2 and/or R3 and R4 may be combined to form each independently ═O or ═CR12AR13A;
M is, each independently if there are plural, C1-6 alkylene, which may be substituted with 1 to 5 the same or different substituents selected from the group consisting of a fluorine atom, chlorine atom, bromine atom, hydroxy, C2-4 alkynyl, C1-3 alkoxy, —CONR36AR37A, —NR36AR37A, —NR36ACOR35A, —NR36ASO2R35A, —SO2R35A, —SO2NR36AR37A, and cyano) C2-6 alkenylene, C2-6 alkynylene, C3-10 cycloalkylene, 3- to 10-membered saturated heterocyclyl, C6-10 arylene, or 5- to 12-membered heteroarylene, wherein the alkenylene, the alkynylene, the cycloalkylene, the saturated heterocyclyl, the arylene, and the heteroarylene may be each independently substituted with 1 to 5 the same or different substituents selected from the group consisting of a fluorine atom, chlorine atom, bromine atom, hydroxy, C1-3 alkyl, C2-4 alkynyl, C1-3 alkoxy, —CONR36AR37A, —NR36AR37A, —NR36ACOR35A, —NR36ASO2R35A, —SO2R35A, —SO2NR36AR37A, and cyano;
Q is, each independently if there are plural, a hydrogen atom, C3-10 cycloalkyl, 3- to 10-membered saturated heterocyclyl, C6-10 aryl, or 5- to 12-membered heteroaryl, wherein the cycloalkyl, the saturated heterocyclyl, the aryl, and the heteroaryl may be each independently substituted with 1 to 5 the same or different substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, hydroxy, C1-3 alkyl, C2-4 alkynyl, C1-3 alkoxy, —CONR36AR37A, —NR36AR37A, —NR36ACOR35A, —NR36ASO2R35A, —SO2R35A, —SO2NR36AR37A, and cyano;
R7 is, each independently if there are plural, a hydrogen atom, C1-6 alkyl, which may be substituted with 1 to 5 the same or different substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, hydroxy, phenyl, 5- to 6-membered heteroaryl, C2-4 alkynyl, C3-7 cycloalkyl, 3- to 7-membered saturated heterocyclyl, C1-3 alkoxy, —CONR36AR37A, —NR36AR37A, —NR36ACOR35A, —NR36ASO2R35A, —SO2R35A, —SO2NR36AR37A, and cyano, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3- to 10-membered saturated heterocyclyl, C6-10 aryl, or 5- to 12-membered heteroaryl, wherein the alkenyl, the alkynyl, the cycloalkyl, the saturated heterocyclyl, the aryl, and the heteroaryl may be each independently substituted with 1 to 5 the same or different substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, hydroxy, C1-3 alkyl, C2-4 alkynyl, C1-3 alkoxy, —CONR36AR37A, —NR36AR37A, —NR36ACOR35A, —NR36ASO2R35A, —SO2R35A, —SO2NR36AR37A, and cyano;
R12A and R13A are each independently a hydrogen atom, a halogen atom, C1-6 alkyl, which may be substituted with 1 to 5 the same or different substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, hydroxy, C2-4 alkynyl, C1-3 alkoxy, —CONR36AR37A, —NR36AR37A, —NR36ACOR35A, —NR36ASO2R35A, —SO2R35A, —SO2NR36AR37A, and cyano, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 3- to 10-membered saturated heterocyclyl, C6-10 aryl, or 5- to 12-membered heteroaryl, wherein the alkenyl, the alkynyl, the cycloalkyl, the saturated heterocyclyl, the aryl, and the heteroaryl may be each independently substituted with 1 to 5 the same or different substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, hydroxy, C1-3 alkyl, C2-4 alkynyl, C1-3 alkoxy, —CONR36AR37A, —NR36AR37A, —NR36ACOR35A, —NR36ASO2R35A, —SO2R35A, —SO2NR36AR37A, and cyano, and if there are plural R12A or R13A, each R12A or R13A may be the same or different, or when R12A and R13A are both C1-6 alkyl, they may be combined with the carbon atom to which they are attached to form 3- to 8-membered saturated carbocycle;
R35A is, each independently if there are plural, C1-6 alkyl;
R36A and R37A are each independently a hydrogen atom or C1-6 alkyl, and if there are plural R36A or R37A, each R36A or R37A may be the same or different, or when R36A and R37A are both C1-6 alkyl, they may be combined with the nitrogen atom to which they are attached to form 3- to 6-membered nitrogen-containing saturated heterocycle;
a, b, c, and d are each independently 1 or 2;
P0 is each independently a hydrogen atom or P1; and
P1 is each independently an amino-protecting group.