1,3,4-oxadiazole sulfonamide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same

An 1,3,4-oxadiazole sulfonamide derivative compound represented by formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

• wherein R1 is —CX2H or —CX3;
• R2 is —(C1-C4 alkyl), —(C1-C4 alkyl)-O(C1-C4 alkyl), —(C1-C4)—C(═O)—O(C1-C4 alkyl), —(C1-C4 alkyl)-O—C(═O)—(C1-C4 alkyl), —(C1-C4 alkyl)-NRARB, —(C1-C4 alkyl)-aryl, —(C1-C4 alkyl)-heteroaryl, -aryl, -heteroaryl,
• wherein at least one H of the —(C1-C4 alkyl), —(C1-C4 alkyl)-O(C1-C4 alkyl), —(C1-C4 alkyl)-C(═O)—O(C1-C4 alkyl), —(C1-C4 alkyl)-O—C(═O)—(C1-C4 alkyl) or —(C1-C4 alkyl)-NRARB may be substituted with —X or —OH,
• at least one H of the —(C1-C4 alkyl)-aryl, —(C1-C4 alkyl)heteroaryl, -aryl or heteroaryl may be substituted with —X, —OH, —O(C1-C4 alkyl), —(C1-C4 alkyl), —CF3, —CF2H, —(C1-C4 alkyl)-OH, —C(═O)—(C1-C4 alkyl), —C(═O)—O(C1-C4 alkyl), —(C1-C4 alkyl)-C(═O)—(C1-C4 alkyl), —C(═O)—CF3 or —C(═O)—CF2H, and at least one H of
• may be substituted with —X, —OH, —O(C1-C4 alkyl), —NRARB, —CN, —(C1-C4 alkyl), —CF3, —CF2H, —(C1-C4 alkyl)-OH, —(C1-C4 alkyl)-NRARB, —C(═O)—(C1-C4 alkyl), —C(═O)—CF3, —C(═O)—CF2H, —C(═O)—NRARB, —C(═O)—O(C1-C4 alkyl), —(C1-C4 alkyl)-C(═O)—(C1-C4 alkyl), —(C1-C4 alkyl)-OC(═O)—CF2H, —(C3-C6 heterocycloalkyl), —(C1-C4 alkyl)-aryl, -aryl or -heteroaryl, wherein at least one H of the —(C1-C4 alkyl)-aryl, -aryl or -heteroaryl may be substituted with —X, —OH, —O(C1-C4 alkyl) or —(C1-C4 alkyl);
• R3 is —H, —(C1-C4 alkyl), —(C1-C4 alkyl)-O(C1-C4 alkyl), —(C1-C4 alkyl)-C(═O)—O(C1-C4 alkyl), -aryl, -heteroaryl,
• wherein at least one H of the —(C1-C4 alkyl), —(C1-C4 alkyl)-O(C1-C4 alkyl) or —(C1-C4 alkyl)-C(═O)—O(C1-C4 alkyl) may be substituted with —X or —OH,
• at least one H of the aryl or -heteroaryl may be substituted with —X, —OH, —O(C1-C4 alkyl), —(C1-C4 alkyl), —CF3, —CF2H, —(C1-C4 alkyl)-OH, —C(═O)—(C1-C4 alkyl), —C(═O)—O(C1-C4 alkyl), —(C1-C4 alkyl)-C(═O)—(C1-C4 alkyl), —C(═O)—CF3, —C(═O)—CF2H,
• at least one H of
• may be substituted with —X, —OH, —O(C1-C4 alkyl), —(C1-C4 alkyl), —C(═O)—(C1-C4 alkyl), —C(═O)—O(C1-C4 alkyl) or —(C3-C6 heterocycloalkyl);
• R4 is —CX2H or —CX3;
• L1 to L4 are each independently a bond or —(C1-C2 alkylene)-;
• Z1 to Z8 are each independently N or CRZ, wherein at least three of Z1 to Z4 or Z5 to Z8 may not be simultaneously N, and RZ is —H, —X or —O(C1-C4 alkyl);
• Z9 and Z10 are each independently N or S;
• Y1 to Y3 are each independently —CH2—, —NRC—, —O— or —S(═O)2—;
• Y4 to Y7 are each independently —CH2—, —NRD— or —O—;
• Y8 is —C(═O), —CH2— or —NRE—;
• Y9 and Y10 are each independently —NRF— or —S(═O)2—;
• RA and RB are each independently —H, —(C1-C4 alkyl), —(C1-C4 alkyl)-aryl, —C(═O)—CF2H or —C(═O)—O(C1-C4 alkyl);
• RC to RE are each independently —H, —(C1-C4 alkyl), —(C1-C4 alkyl)-OH, —(C1-C4 alkyl)-O—(C1-C4 alkyl), —C(═O)—(C1-C4 alkyl), —C(═O)—O(C1-C4 alkyl), —C(═O)—(C3-C7 cycloalkyl), —(C1-C4 alkyl)-C(═O)—(C2-C6 heterocycloalkyl), —S(═O)2—(C1-C4 alkyl), —(C1-C4 alkyl)-aryl, —(C2-C4 alkenyl)-aryl, —(C1-C4 alkyl)-heteroaryl, -aryl, -heteroaryl,
• wherein at least one H of the —(C1-C4 alkyl)-aryl, —(C2-C4 alkenyl)-aryl, —(C1-C4 alkyl)-heteroaryl, -aryl, -heteroaryl,
• may be substituted with —X, —OH, —O(C1-C4 alkyl), —(C1-C4 alkyl) or —CF3;
• Y11 is —CH2—, —NRF— or —O—;
• RF is —(C1-C4 alkyl), —C(═O)—(C1-C4 alkyl), —C(═O)—(C1-C4 alkyl)-OH, —C(═O)—(C3-C7 cycloalkyl) or —S(═O)2—(C1-C4 alkyl);
• is a single bond or a double bond, provided that is a double bond, Y1 or Y2 is —CH—;
• a to e are each independently an integer of 0, 1, 2 or 3, provided that a and b may not be simultaneously 0, and c and d may not be simultaneously 0;
• and
• X is F, Cl, Br or I.