US 12,110,287 B2
Heterocyclic derivatives as Nav1.7 and Nav1.8 blockers
Tatsuya Yamagishi, Aichi (JP); Kiyoshi Kawamura, Aichi (JP); Yuji Shishido, Aichi (JP); Ryuichi Yamaguchi, Aichi (JP); Mikio Morita, Aichi (JP); and Norikazu Gaja, Aichi (JP)
Assigned to RaQualia Pharma Inc., Aichi (JP)
Appl. No. 17/417,182
Filed by RaQualia Pharma Inc., Aichi (JP)
PCT Filed Dec. 26, 2019, PCT No. PCT/JP2019/051086
§ 371(c)(1), (2) Date Jun. 22, 2021,
PCT Pub. No. WO2020/138271, PCT Pub. Date Jul. 2, 2020.
Claims priority of provisional application 62/784,881, filed on Dec. 26, 2018.
Prior Publication US 2022/0048892 A1, Feb. 17, 2022
Int. Cl. C07D 401/14 (2006.01); A61K 31/395 (2006.01); A61K 31/435 (2006.01); A61K 45/06 (2006.01); C07D 401/12 (2006.01)
CPC C07D 401/14 (2013.01) [A61K 31/395 (2013.01); A61K 31/435 (2013.01); A61K 45/06 (2013.01); C07D 401/12 (2013.01)] 10 Claims
 
1. A compound of the following formula (I):

OG Complex Work Unit Chemistry
wherein:
A is phenyl, pyridyl, or quinolyl;
R1 is selected from the group consisting of: C1-6 alkyl, —O—C1-6 alkyl, and fluorobenzyloxy; wherein the C1-6 alkyl or the —O—C1-6 alkyl, is substituted with one or more fluorines;
R2 is independently selected from the group consisting of: (1) hydrogen, (2) halogen, (3) hydroxyl, (4) C1-6 alkyl, (5) —OC1-6 alkyl, and (6) —CN; wherein the C1-6 alkyl or the —O—C1-6 alkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of: halogen and hydroxyl;
P is 0, 1, 2, 3, or 4;
when p is two or more, each R2 is the same or different;
R1 and R2 may substitute anywhere on the A ring;
n is 1, 2, or 3;
Z is CH, CR3, or N;
R3 is independently selected from the group consisting of:
(1) hydrogen, (2) halogen, (3) hydroxyl, (4) C1-6 alkyl, and (5) —O—C1-6 alkyl;
q is 0, 1, 2, or 3; when q is two or more, each R3 is the same or different;
R4 is selected from the group consisting of:
(1) C1-6 alkyl and (2) C3-7 cycloalkyl, wherein the C1-6 alkyl or the C3-7 cycloalkyl is unsubstituted or substituted with one or more substituents independently selected form the group consisting of: halogen, hydroxyl, C1-6 alkyl, —O—C1-6 alkyl, and C3-7 cycloalkyl;
R5a and R5b are independently selected from the group consisting of:
(1) hydrogen, (2) halogen, (3) hydroxyl, and (4) C1-6 alkyl, which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of: halogen and hydroxyl;
R5a and R5b may substitute anywhere on the carbon atoms of the heterocyclic ring;
when R5a and R5b substitute at the same position, R5a may form a 3 to 6 membered cycloalkyl ring with R5b; and
R5c, is (1) hydrogen or (2) C1-6 alkyl;
or a pharmaceutically acceptable salt thereof.