US 12,030,880 B2
Iminosulfanone compound as bromodomain protein inhibitor and pharmaceutical composition and medical use thereof
Jijun Li, Beijing (CN); Yan Zhu, Beijing (CN); Yeliu Wang, Beijing (CN); Xianxing Shang, Beijing (CN); Huting Wang, Beijing (CN); Weinan He, Beijing (CN); Qin Yan, Beijing (CN); Yinghui Sun, Beijing (CN); Kai Zhang, Beijing (CN); Chang Lu, Beijing (CN); Hongjiang Xu, Lianyungang (CN); Xin Tian, Lianyungang (CN); and Ling Yang, Lianyungang (CN)
Assigned to Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Lianyungang (CN); Shouyao Holdings (Beijing) Co., Ltd., Beijing (CN); and Lianyungang Runzhong Pharmaceutical Co., Ltd., Lianyungang (CN)
Appl. No. 17/262,053
Filed by CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD., Lianyungang (CN); SHOUYAO HOLDINGS (BEIJING) CO., LTD., Beijing (CN); and LIANYUNGANG RUNZHONG PHARMACEUTICAL CO., LTD., Lianyungang (CN)
PCT Filed Jul. 25, 2019, PCT No. PCT/CN2019/097692
§ 371(c)(1), (2) Date Jan. 21, 2021,
PCT Pub. No. WO2020/020288, PCT Pub. Date Jan. 30, 2020.
Claims priority of application No. 201810825047.X (CN), filed on Jul. 25, 2018; and application No. 201910410273.6 (CN), filed on May 17, 2019.
Prior Publication US 2021/0300923 A1, Sep. 30, 2021
Int. Cl. C07D 471/04 (2006.01); A61P 35/02 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 35/02 (2018.01)] 18 Claims
 
1. A compound of formula I or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein,
R1 is selected from the group consisting of H, C1-C3 alkyl, and C1-C3 acyl, the C1-C3 alkyl or C1-C3 acyl is optionally substituted with one or more halogens;
Y is selected from the group consisting of O, S, and NRY, the RY is selected from the group consisting of H, C1-C3 alkyl, and C1-C3 acyl, the C1-C3 alkyl or C1-C3 acyl is optionally substituted with one or more halogens;
X1 is selected from the group consisting of N and CRX1, the RX1 is selected from the group consisting of H, C1-C6 alkyl, halogen, and C1-C6 haloalkyl;
X2 is selected from the group consisting of N and CRX2, and X3 is selected from the group consisting of N and CRX3, the RX2 and RX3 are each independently selected from the group consisting of H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —C(O)ORa, —C(O)NRbRc, —C(O)Rd, —S(O)2Re, and —S(O)2NRbRc, the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more halogen, hydroxyl, amino, nitro, or cyano;
Z1 is N, Z2 is selected from the group consisting of N and CRZ2, and Z3 is selected from the group consisting of N and CRZ3, the RZ2, and RZ3 are each independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, cyano, and nitro, the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more halogens, hydroxyl, amino, nitro, or cyano; or
Z1 is selected from the group consisting of N and CRZ1, Z2 is N, and Z3 is selected from the group consisting of N and CRZ3, the RZ1 and RZ3 are each independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, cyano, and nitro, the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more halogens, hydroxyl, amino, nitro, or cyano; or
Z1 is selected from the group consisting of N and CRZ1, Z2 is selected from the group consisting of N and CRZ2, and Z3 is N, the RZ1 and RZ2 are each independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, cyano, and nitro, the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more halogens, hydroxyl, amino, nitro, or cyano;
R2 and R3 are each independently selected from the group consisting of halogen, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkylamino, and (C1-C6 alkyl)2 amino, the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkylamino, or (C1-C6 alkyl)2 amino is optionally substituted with one or more halogens, hydroxyl, amino, nitro, or cyano; or
R2 and R3 are connected and form a 3-8 membered heterocycloalkyl together with an adjacent S atom, the 3-8 membered heterocycloalkyl optionally contains 1-3 heteroatoms selected from the group consisting of N, O, and S, in addition to the S atom to which R2 and R3 are both connected; and the ring carbon atoms of the 3-8 membered heterocycloalkyl are optionally substituted with one or more halogens, hydroxyl, amino, nitro, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylamino, or (C1-C6 alkyl)2 amino, or substituted with one or more oxo;
L is selected from the group consisting of a single bond, —O—, —NH—, —(C1-C3 alkyl)-O—, —(C1-C3 alkyl)-NH—, and —C1-C3 alkyl-; and
R4 is selected from the group consisting of C6-C10 aryl, C3-C10 cycloalkenyl, C3-C10 cycloalkyl, 3-10 membered heteroaryl, 3-10 membered heterocycloalkenyl, and 3-10 membered heterocycloalkyl, the 3-10 membered heteroaryl, 3-10 membered heterocycloalkenyl, or 3-10 membered heterocycloalkyl each independently contains 1-3 heteroatoms selected from the group consisting of N, O, and S; and R4 is optionally substituted with one or more halogens, hydroxyl, amino, nitro, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkylamino, (C1-C6 alkyl)2 amino, —C(O)ORa, —C(O)NRbRc, —C(O)Rd, —S(O)2Re, —NHS(O)2Re, or —S(O)2NRbRc, or substituted with one or more oxo;
the Ra, Rb, Rc, Rd, and Re are each independently selected from the group consisting of H, C1-C6 alkyl, and C1-C6 haloalkyl.