US 11,999,746 B2
Compounds
Zehong Wan, Shanghai (CN); Xiaomin Zhang, Shanghai (CN); Jian Wang, Shanghai (CN); Matthew Robert Sender, Collegeville, PA (US); Eric Steven Manas, Collegeville, PA (US); Raphael Anthony Rivero, Collegeville, PA (US); Joseph E Pero, Collegeville, PA (US); Christopher Ernst Neipp, Collegeville, PA (US); and Vipulkumar Kantibhai Patel, Stevenage (GB)
Assigned to GlaxoSmithKline Intellectual Property Development Limited, (GB)
Filed by GlaxoSmithKline Intellectual Property Development Limited, Brentford (GB)
Filed on Jul. 29, 2019, as Appl. No. 16/524,238.
Application 16/524,238 is a continuation of application No. 16/143,788, filed on Sep. 27, 2018, granted, now 10,428,078.
Application 16/143,788 is a continuation of application No. 15/327,706, granted, now 10,125,141, previously published as PCT/CN2015/084606, filed on Jul. 21, 2015.
Claims priority of application No. PCT/CN2014/000695 (WO), filed on Jul. 22, 2014.
Prior Publication US 2020/0055863 A1, Feb. 20, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 487/14 (2006.01); C07D 471/14 (2006.01); C07D 471/20 (2006.01); C07D 487/04 (2006.01); C07D 491/20 (2006.01); C07D 498/14 (2006.01); C07D 513/14 (2006.01)
CPC C07D 487/14 (2013.01) [C07D 471/14 (2013.01); C07D 471/20 (2013.01); C07D 487/04 (2013.01); C07D 491/20 (2013.01); C07D 498/14 (2013.01); C07D 513/14 (2013.01); H05K 999/99 (2013.01)] 14 Claims
 
1. A compound or a pharmaceutically acceptable salt thereof having the structure of Formula (I-4)

OG Complex Work Unit Chemistry
wherein
R1 is selected from the group consisting of H, C1-3alkyl, and —C(O)—C1-3alkyl; and
R2 and R3 together with the carbon to which they are attached form a 4-, 5- or 6-membered saturated ring, which ring
optionally contains one heteroatom ring member selected from N or O, and
is optionally substituted with one substituent of -L-K, wherein
L is selected from the group consisting of C(O), CH2, and S(O)2, and
K is selected from the group consisting of C1-3alkyl, phenyl, and C3-6cycloalkyl;
or R1 and R2 together with the nitrogen and carbon to which they are attached form a 6-membered saturated ring, which ring
optionally contains one or two additional heteroatom ring members independently selected from the group consisting of N, O, C(O), S, S(O), and S(O)2, and
is optionally substituted with one or more substituents independently selected from the group consisting of OH, halo, NR1aR1b, COOH, and —Y—Rc, wherein
Y is absent or is selected from the group consisting of C(O), S(O)2, —C(O)—C(O)—, and CH2, and
Rc is selected from the group consisting of
 C1-5alkyl optionally substituted with one or more substituents independently selected from the group consisting of NR2aR2b, C3-6 cycloalkyl, and —COOH,
 C1-3haloalkyl,
 C1-3alkoxyl,
 NR3aR3b,
 —(CH2)p—C(O)—O—C1-3alkyl, wherein p is 1, 2, or 3 and the —(CH2)p— is optionally substituted by one or more methyl,
 —(CH2)q—C3-6 cycloalkyl, wherein q is 1, 2, or 3, the cycloalkyl is optionally substituted with NR4aR4b, and the —(CH2)q— is optionally substituted by one or more methyl, and
 heterocyclyl optionally substituted with one or more substituents independently selected from the group consisting of halo and NR5aR5b,
wherein R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5a, and R5b are independently H or C1-3alkyl; and
R3 is H;
each occurrence of R4 is independently H or D;
X is absent or is selected from the group consisting of
—O—,
—NH—, and
—N(C1-3 alkyl)-,
n is 1 or 2; or
X is —O—CH2-bicyclo[1.1.1]pentanyl-CH2—O— and n is 0; and
A is unsubstituted thiophenyl, or
A is

OG Complex Work Unit Chemistry
wherein
R5 and R9 are independently H or halo,
Z′ is N or CR6,
Z is N or CR8,
wherein R6 and R8 are independently selected from the group consisting of H, CN, halo, C1-3alkyl, C1-3haloalkyl, —S(O)2—C1-3alkyl and —S(O)—C1-3alkyl, and
V is CR7, wherein R7 is -Q-(CH2)m—W, wherein
Q is O, N, or CH2,
m is 0 or 1, and
W is pyridyl, and
wherein said pyridyl is optionally substituted with one or more substituents independently selected from the group consisting of C1-3haloalkyl, CN, halo, and C1-5 alkyl.