US 11,053,235 B2
Substituted 1,4-dihydropyrimidines for the treatment of HBV infection or HBV-induced diseases
Gang Deng, Shanghai (CN); Yimin Jiang, Londonberry, NH (US); Qian Liu, Shanghai (CN); Chao Liang, Shanghai (CN); Zhao-Kui Wan, Shanghai (CN); Wing Shun Cheung, Shanghai (CN); Zhanling Cheng, Shanghai (CN); and Yanping Xu, Noblesville, IN (US)
Assigned to Janssen Sciences Ireland Unlimited Company, County Cork (IE)
Filed by Janssen Sciences Ireland Unlimited Company, County Cork (IE)
Filed on Aug. 9, 2019, as Appl. No. 16/537,395.
Claims priority of provisional application 62/716,823, filed on Aug. 9, 2018.
Prior Publication US 2020/0048242 A1, Feb. 13, 2020
Int. Cl. A61K 31/505 (2006.01); C07D 239/20 (2006.01); C07D 417/14 (2006.01); A61K 45/06 (2006.01); A61K 38/17 (2006.01); A61K 31/675 (2006.01); C07K 16/28 (2006.01); A61K 31/7068 (2006.01)
CPC C07D 417/14 (2013.01) [A61K 31/675 (2013.01); A61K 31/7068 (2013.01); A61K 38/1793 (2013.01); A61K 45/06 (2013.01); C07K 16/2818 (2013.01)] 17 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
L1 is a bond or C1-C4 alkylene, wherein the C1-C4 alkylene is optionally substituted with one or more substituents independently selected from the group consisting of oxo, halogen, C1-C4 alkyl, C1-C4 haloalkyl, and OR7;
L2 is a bond, C1-C4 alkylene, or a 3- to 7-membered saturated ring, wherein the 3- to 7-membered saturated ring optionally comprises one or more nitrogen heteroatoms, and further wherein the C1-C4 alkylene and 3- to 7-membered saturated ring are each optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 haloalkyl, and OR15;
Y4 is R14, OH, or OR14;

OG Complex Work Unit Chemistry
is a 5- or 6-membered aromatic ring, wherein the 5- or 6-membered aromatic ring optionally comprises 1, 2, or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, and further wherein the 5- or 6-membered aromatic ring is optionally substituted with one or more substituents independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkyl-OR12, NR10R11, and OR13;

OG Complex Work Unit Chemistry
is selected from the group consisting of:

OG Complex Work Unit Chemistry
wherein:
each R7 is independently H, C1-C4 alkyl, or C1-C4 haloalkyl;
each R8 is independently H or C1-C4 alkyl;
R9 is H or C1-C4 alkyl;
A is CH or N; and
Y3 is CH or C;
R1 is thiazolyl or pyridyl, wherein the thiazolyl and pyridyl are each optionally substituted with one or more independently selected halogen substituents;
R3 is C1-C3 alkyl;
R4 is H, halogen, or C1-C3 alkyl;
R5 is H, halogen, or C1-C3 alkyl;
R6 is H, halogen, or C1-C3 alkyl;
each R10 is independently H or C1-C4 alkyl;
each R11 is independently H or C1-C4 alkyl; or
R10 and R11, together with the nitrogen atom to which they are attached, form a ring, wherein the ring comprises 4, 5, or 6 carbon atoms;
each R12 is independently H or C1-C4 alkyl;
each R13 is independently H or C1-C4 alkyl;
R14 is C1-C4 alkyl;
each R15 is independently H or C1-C4 alkyl; and
p is 0 or 1.
 
13. A pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and the compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.