Sigma-1 receptor ligands and use thereof

A compound having the following formula (I), an isomer thereof, or a pharmaceutical acceptable solvate thereof,

• wherein
• R1 is
• R2 is
• R1a, R1b, R1c, R1d, R1e, R2a, R2b, R2c, R2d, and R2e are each independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —OH, —OCH3, —CH3, —CF3, —CHF2, —CH2F, —CD3, —CN, and
• R3 and R4 are independently selected from the group consisting of —CH3, —CD3, —CF3, —CHF2, —CH2F, —(CH2)n—O—R5, and —CO—R6, n is 1 or 2, provided that when R1a, R1b, R1c, R1d, R1e, R2a, R2b, R2c, R2d, and R2e are all —H, at least one of R3 and R4 is —CD3, —CF3, —CHF2, —CH2F, —(CH2)n—O—R5, or —CO—R6;
• or R3 and R4 form a 5-membered or 6-membered heterocyclyl group;
• and
• R5 is
• —CO—CH(R5b)—(CH2)m—R5c, or —CH2—R5d;
• R5a is —H or a C1-6 alkyl group;
• R5b is —H, —NH2 or
• m is 0, 1, 2, or 3, R5c is —COOH, —CONH2, —NH2, —NH—CO—CH2—NH2,
• Rx is —OH, —NH2, —F, —Cl, —Br, or —CN;
• R5d is —CH2CH2NH2, —CH2CH2CONH2,
• Ry is —OH, —NH2, —F, —Cl, —Br, or —CN;
• and
• R6 is —CH2CH2NH2, —CH2CH2CONH2,