US 12,263,172 B2
Toll-like receptor agonists for use in the treatment of hepatitis b
Peter Jozef M Van Remoortere, Raritan, NJ (US); Sean Mark Dalziel, Burlingame, CA (US); Ilham Smyej, Beerse (BE); Joris Jozef Vandenbossche, Beerse (BE); An Martine M De Creus, Beerse (BE); Mina Pastagia, South San Francisco, CA (US); and Florence Marie Herschke, Beerse (BE)
Assigned to CHIA TAI TIANQING PHARMECEUTICAL GROUP CO., LTD., Lianyungang (CN)
Appl. No. 17/439,280
Filed by CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD., Jiangsu (CN)
PCT Filed Mar. 13, 2020, PCT No. PCT/IB2020/052328
§ 371(c)(1), (2) Date Sep. 14, 2021,
PCT Pub. No. WO2020/188448, PCT Pub. Date Sep. 24, 2020.
Claims priority of provisional application 62/819,033, filed on Mar. 15, 2019.
Prior Publication US 2022/0249488 A1, Aug. 11, 2022
Int. Cl. A61K 31/519 (2006.01)
CPC A61K 31/519 (2013.01) 20 Claims
 
1. A method of treating an HBV infection in a human subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising at least one TLR-7 agonist and at least one pharmaceutically acceptable excipient;
wherein the TLR-7 agonist is a compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof;
wherein:
L1 is —O—;
L2 is —CH2—;
R1 is selected from the group consisting of —H and —C1-C10 alkyl; wherein the alkyl is optionally substituted by one or more R4 groups;
R2 is selected from the group consisting of —H, —N, —COOH, and —CONH2;
ring A is selected from the group consisting of aryl and heteroaryl;
L3 is selected from the group consisting of C0-C6 alkylene and imino; wherein alkylene and imino are optionally substituted by one or more R4 groups;
R3 is selected from the group consisting of —H, amino, C1-C10 alkyl, C3-C10 cycloalkyl, and 3-10 membered heterocycloalkyl; wherein amino, alkyl, cycloalkyl, and heterocycloalkyl are optionally substituted by one or more R4 groups;
or wherein R3 and L3, together with the atom to which L3 is attached and the adjacent atom in ring A, form a saturated or unsaturated 5-8 membered ring, which is optionally substituted by one or more R4 groups;
R4 is, independently at each occurrence, selected from the group consisting of —R, —OR, and ═O; and
R is, independently at each occurrence, selected from the group consisting of H and C1-C8 alkyl;
wherein the compound of Formula I is administrated at a dose of 0.2 to 1.8 mg each time.