US 12,466,827 B2
1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same
Chang Kon Lee, Yongin-si (KR); Moo Sung Ko, Yongin-si (KR); Dal-Yong Gwak, Yongin-si (KR); Seok Hyoun Yun, Yongin-si (KR); Seo Young Lee, Yongin-si (KR); and Hyunjin Michael Kim, Yongin-si (KR)
Assigned to CHONG KUN DANG PHARMACEUTICAL CORP., Seoul (KR)
Appl. No. 17/904,806
Filed by CHONG KUN DANG PHARMACEUTICAL CORP., Seoul (KR)
PCT Filed Feb. 25, 2021, PCT No. PCT/KR2021/002362
§ 371(c)(1), (2) Date Aug. 23, 2022,
PCT Pub. No. WO2021/172886, PCT Pub. Date Sep. 2, 2021.
Claims priority of application No. 10-2020-0023249 (KR), filed on Feb. 25, 2020.
Prior Publication US 2023/0147859 A1, May 11, 2023
Int. Cl. C07D 471/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 519/00 (2013.01)] 12 Claims
 
1. A 1,3,4-oxadiazole derivative compound represented by Chemical Formula I below, an optical isomer thereof, or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
in the Chemical Formula I above,
L1, L2 and L3 are each independently —(C0-C2alkyl)-;
a, b and c are each independently N or CR4 {wherein a, b and c cannot be N at the same time, and R4 is —H, —X or —O(C1-C4alkyl)};
R1 is —CX2H or —CX3;
R2 is —(C1-C4alkyl), —(C1-C4alkyl)-O—(C1-C4alkyl), —NRARB, aryl, heteroaryl,

OG Complex Work Unit Chemistry
Y is —N—, —CH—, —O—or —S(═O)2—;
when Y is —N—or —CH—, R5, R6, R7 and R8 are each independently —H, —X, —OH, —(C1-C4alkyl), —(C1-C4alkyl)-O(C1-C4alkyl), —(C3-C7cycloalkyl), —(C2-C6heterocycloalkyl), —O(C1-C4alkyl), —NRCRD, —CF3, —CF2H, —CN, —C(═O)—(C1-C4alkyl), —C(═O)—(C3-C7cycloalkyl), —C(═O)—(C2-C6heterocycloalkyl), —C(═O)—O(C1-C4alkyl), —(C1-C4alkyl)-C(═O)—O(C1-C4alkyl), —C(═O)—NRCRD, —C(═O)—(C1-C4alkyl)-NRCRD, —S(═O)2—(C1-C4alkyl), -aryl, -heteroaryl, —(C1-C4alkyl)-aryl, —(C1-C4alkyl) heteroaryl, an amine protecting group or

OG Complex Work Unit Chemistry
{wherein at least one H of —(C1-C4alkyl), —(C═O)—(C1-C4alkyl), —(C3-C7cycloalkyl) and —C(═O)—(C3-C7cycloalkyl) may be substituted with —X, —OH, —O(C1-C4alkyl), —C(═O)—(C1-C4alkyl), —C(═O)—O(C1-C4alkyl), —CF3 or —CF2H; at least one H of -aryl, -heteroaryl, —(C1-C4alkyl)-aryl and —(C1-C4alkyl) heteroaryl may be substituted with —X, —OH, —(C1-C4alkyl), —O(C1-C4alkyl), —C(═O)—(C1-C4alkyl), —C(═O)—O(C1-C4alkyl), —CF3 or —CF2H; —(C2-C6heterocycloalkyl), -heteroaryl or —(C1-C4alkyl) heteroaryl may contain N, O or S atom in the ring; and Z is —NH—, —CH2—or —O—};
when Y is —O—or —S(═O)2—, R5, R6, R7 and R8 are nothing (null);
RA to RD are each independently —H, —(C1-C4alkyl), —(C3-C7cycloalkyl), —(C2-C6heterocycloalkyl), —(C1-C4alkyl)-(C2-C6heterocycloalkyl), aryl, heteroaryl or —(C1-C4alkyl)-aryl {wherein at least one H of —(C3-C7cycloalkyl), —(C2-C6heterocycloalkyl), —(C1-C4alkyl)-(C2-C6heterocycloalkyl), aryl, heteroaryl and —(C1-C4alkyl)-aryl may be substituted with —(C1-C4alkyl), —C(═O)—(C1-C4alkyl), —S(═O)2—(C1-C4alkyl) or —(C2-C6heterocycloalkyl)};
m and n are each independently an integer of 1,2 or 3;
Ra to Rd are each independently —H or —(C1-C4alkyl);
R3 is —H, —(C1-C4alkyl), —(C1-C4alkyl)-O(C1-C4alkyl), —(C1-C4alkyl)-C(═O)—O(C1-C4alkyl), —C(═O)—O(C1-C4alkyl), —(C3-C7cycloalkyl), —(C2-C6heterocycloalkyl), -aryl or -heteroaryl {wherein at least one H of —(C1-C4alkyl), —(C3-C7cycloalkyl), —(C2-C6heterocycloalkyl), -aryl and -heteroaryl may each independently be substituted with —X, —OH, —O(C1-C4alkyl), —C(═O)—O(C1-C4alkyl), —C(═O)—(C1-C4alkyl), —CF3, —CF2H, —OCF3, —S(═O)2—(C1-C4alkyl), -aryl, —O-aryl, -heteroaryl or —NRERF, and the RE and RF are each independently —H or —(C1-C4alkyl)}; and
X is F, Cl, Br or I.