Fused tricyclic Γ-amino acid derivative, preparation method therefor, and medical use thereof

A pharmaceutical composition, comprising:

• a compound corresponding to general formula (I) or stereoisomers, solvates, pharmaceutically acceptable salts, or prodrugs thereof;
• and one or more pharmaceutically acceptable carriers and/or excipients;
• thereof,
• wherein R1 and R4 bond each other to form —(CR9R9′)n- or —CR9=CR9′—;
• R1′, R2, R3, R3′, R4′, R5, R5′, R6, R9 or R9′ is each independently selected from H, F, Cl, Br, I, hydroxyl, amino, carboxy, carboxylate, amide group, cyano, a C1-6 alkyl, a C1-6 alkoxy, a C1-6 sulfanyl, a C2-6 alkenyl, a C2-6 alkynyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, wherein the alkyl, alkoxy, sulfanyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, carboxy, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, and the heterocyclyl contains 1 to 2 heteroatoms selected from N, O or S;
• n is selected from 1, 2 or 3;
• alternatively, any pair of R3 and R3′, R5 and R5′, and R9 and R9′ forms
• together with the carbon atom to which they are attached, and the
• is optionally further substituted with 0 to 2 substituents selected from F, Cl, Br, I, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, wherein the alkyl, 3- to 6-membered carbocyclyl or 3- to 6-membered heterocyclyl is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, carboxy, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl;
• alternatively, any pair of R3 and R3′, R5 and R5′, and R9 and R9′ forms a 3- to 6-membered carbocycle together with the carbon atom to which they are attached, and the carbocycle is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, a C1-6 alkyl, a C1-6 alkoxy, or a C1-6 sulfanyl;
• R7 is selected from H, a C1-6 alkyl, or an amino-protecting group;
• and
• R8 is selected from H, a C1-6 alkyl, or a carboxy-protecting group.

A method for treating and/or preventing pain comprising administering the pharmaceutical composition, which comprises one or more pharmaceutically acceptable carriers and/or excipients;

• and
• an effective amount of a compound corresponding to general formula (I) or stereoisomers, solvates, pharmaceutically acceptable salts, or prodrugs thereof;
• wherein R1 and R4 bond each other to form —(CR9R9′)n- or —CR9=CR9′—;
• R1′, R2, R3, R3′, R4′, R5, R5′, R6, R9 or R9′ is each independently selected from H, F, Cl, Br, I, hydroxyl, amino, carboxy, carboxylate, amide group, cyano, a C1-6 alkyl, a C1-6 alkoxy, a C1-6 sulfanyl, a C2-6 alkenyl, a C2-6 alkynyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, wherein the alkyl, alkoxy, sulfanyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, carboxy, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, and the heterocyclyl contains 1 to 2 heteroatoms selected from N, O or S;
• n is selected from 1, 2 or 3;
• alternatively, any pair of R3 and R3′, R5 and R5′, and R9 and R9′ forms
• together with the carbon atom to which they are attached, and the
• is optionally further substituted with 0 to 2 substituents selected from F, Cl, Br, I, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, wherein the alkyl, 3- to 6-membered carbocyclyl or 3- to 6-membered heterocyclyl is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, carboxy, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl;
• alternatively, any pair of R3 and R3′, R5 and R5′, and R9 and R9′ forms a 3- to 6-membered carbocycle together with the carbon atom to which they are attached, and the carbocycle is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, a C1-6 alkyl, a C1-6 alkoxy, or a C1-6 sulfanyl;
• R7 is selected from H, a C1-6 alkyl, or an amino-protecting group;
• and
• R8 is selected from H, a C1-6 alkyl, or a carboxy-protecting group.

A compound of general formula (Z), or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

• R1 and R4 bond each other to form —(CR9R9′)n- or —CR9=CR9′—;
• R1′, R2, R3, R3′, R4′, R5, R5′, R6, R9 or R9′ is each independently selected from H, F, Cl, Br, I, hydroxyl, amino, carboxy, carboxylate, amide group, cyano, a C1-6 alkyl, a C1-6 alkoxy, a C1-6 sulfanyl, a C2-6 alkenyl, a C2-6 alkynyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, wherein the alkyl, alkoxy, sulfanyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, carboxy, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, and the heterocyclyl contains 1 to 2 heteroatoms selected from N, O or S;
• n is selected from 2 or 3;
• alternatively, any pair of R3 and R3′, R5 and R5′, and R9 and R9′ forms
• together with the carbon atom to which they are attached, and the
• is optionally further substituted with 0 to 2 substituents selected from F, Cl, Br, I, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl, wherein the alkyl, 3- to 6-membered carbocyclyl or 3- to 6-membered heterocyclyl is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, carboxy, a C1-6 alkyl, a 3- to 6-membered carbocyclyl or a 3- to 6-membered heterocyclyl;
• alternatively, any pair of R3 and R3′, R5 and R5′, and R9 and R9′ forms a 3- to 6-membered carbocycle together with the carbon atom to which they are attached, and the carbocycle is optionally further substituted with 0 to 6 substituents selected from F, Cl, Br, I, hydroxyl, amino, a C1-6 alkyl, a C1-6 alkoxy, or a C1-6 sulfanyl;
• alternatively, n is 1, R3 and R3′ are F, Cl, Br or I, or R3 and R3′ form
• together with the carbon atom to which they are attached, or R3 and R3′ form a 3- to 6-membered carbocycle together with the carbon atom to which they are attached.