US 12,336,996 B2
Drug combination containing TLR7 agonist
Hongjiang Xu, Nanjing (CN); Dandan Lu, Nanjing (CN); Xingfeng Ge, Nanjing (CN); Wei Song, Nanjing (CN); Wei Shi, Nanjing (CN); Ling Yang, Nanjing (CN); Xiquan Zhang, Nanjing (CN); Hao Yu, Nanjing (CN); and Zhongnan Xu, Nanjing (CN)
Assigned to Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Lianyungang (CN)
Appl. No. 17/754,099
Filed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Lianyungang (CN)
PCT Filed Sep. 29, 2020, PCT No. PCT/CN2020/118693
§ 371(c)(1), (2) Date Mar. 23, 2022,
PCT Pub. No. WO2021/058021, PCT Pub. Date Apr. 1, 2021.
Claims priority of application No. 201910933558.8 (CN), filed on Sep. 29, 2019.
Prior Publication US 2023/0015906 A1, Jan. 19, 2023
Int. Cl. A61K 31/519 (2006.01); A61K 9/28 (2006.01); A61K 31/52 (2006.01); A61P 31/12 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 9/2893 (2013.01); A61K 31/52 (2013.01); A61P 31/12 (2018.01)] 19 Claims
 
1. A pharmaceutical combination, comprising a compound of formula I or a pharmaceutically acceptable salt thereof and entecavir or a pharmaceutically acceptable salt or solvate thereof, wherein the compound of formula I is shown as follows:

OG Complex Work Unit Chemistry
wherein,
L1 is selected from —O—;
L2 is selected from —CH2—, wherein the —CH2— is optionally substituted with R4;
R1 is selected from the group consisting of hydrogen and C1-10 alkyl, wherein the C1-10 alkyl is optionally substituted with R5;
R2 is selected from the group consisting of hydrogen, cyano, —COOH and —CONH2, wherein the —COOH and —CONH2 are optionally substituted with R6;
B is selected from the group consisting of 6-10 membered aryl and 5-10 membered heteroaryl;
L3 is selected from the group consisting of C0-6 alkylene and imino, wherein the C0-6 alkylene and imino are optionally substituted with R7;
R3 is selected from the group consisting of hydrogen, amino, C1-10 alkyl, C3-10 cyclohydrocarbyl, 3-10 membered heterocyclohydrocarbyl, 6-10 membered aryl and 5-10 membered heteroaryl, wherein the amino, C1-10 alkyl, C3-10 cyclohydrocarbyl, 3-10 membered heterocyclohydrocarbyl, 6-10 membered aryl and 5-10 membered heteroaryl are optionally substituted with R8, or
R3 and L3, together with an ortho atom on ring B, form a saturated or unsaturated 5-8 membered ring, wherein the 5-8 membered ring is optionally substituted with R9;
n is 0, 1, 2, 3, 4 or 5;
R4, R5, R6, R7, R8 and R9 are each independently selected from halogen, cyano, hydroxy, sulfydryl, amino, —R, —OR, —O, —SR, —NHR and —NR2; R is independently selected from the group consisting of C1-8 alkyl, C3-8 cyclohydrocarbyl, 3-8 membered heterocyclohydrocarbyl, 6-8 membered aryl and 5-8 membered heteroaryl.