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

BR112021023770B1Active Publication Date: 2026-09-15CHONG KUN DANG PHARMACEUTICAL CORP

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Patent Information

Application Number: BR112021023770
Authority / Receiving Office: BR · BR
Patent Type: Patents
Current Assignee / Owner
Publication Date: 2026-09-15

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Abstract

1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitors and the pharmaceutical composition comprising the same. The present invention relates to 1,3,4-oxadiazole derivative compounds with histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, a use thereof in the preparation of a medicament, a pharmaceutical composition comprising the same, a therapeutic method using the composition, and a method for preparing the same, and the 1,3,4-oxadiazole derivative compounds are represented by the following chemical formula i.

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Claims

1. Compounds represented by the following chemical formula I or pharmaceutically acceptable salts thereof: [Chemical Formula I] characterized in that Z1 to Z4 are each independently N or CRa, wherein Ra is H, X, C1-C4 alkyl or O-(C1-C4 alkyl) and Ra may differ from each other when CRa is 2 or more; K is O or S; R1 is CX3 or CX2H; AA is C6-C12 arylene or C2-C10 heteroarylene; R2 and R3 are each independently H, X, C1-C4 alkyl, C1-C4 haloalkyl, C6-C12 aryl, C2-C10 heteroaryl, C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, C2-C10 heterocycloalkenyl, N(Rb)(Rc), NH-(C1-C4 alkyl)-N(Rb)(Rc), NH-O-(C1-C4 alkyl) or NHC(=O)-R5, wherein at least one H of C1-C4 alkyl, C6-C12 aryl, C2-C10 heteroaryl, C2-C10 heterocycloalkenyl or C2-C10 heterocycloalkyl may each be independently substituted with X, C1-C4 alkyl, C1-C4 haloalkyl, C3-C10 870260052856, dated 01 / 06 / 2026, page 56 / 102 2 / 47 cycloalkyl, C6-C12 aryl, C2-C10 heteroaryl,C2-C10 heterocycloalkyl, (C1-C4 alkyl)-(C2-C10 heteroaryl), (C1-C4 alkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl), (C2-C10 heterocycloalkyl)-(C1-C4 haloalkyl), (C2-C10 heterocycloalkyl)-(C3-C10 cycloalkyl), (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl)-(C3-C10 halocycloalkyl), (C1-C4 alkyl)-(C3-C10 cycloalkyl), S(O2)-(C1-C4 alkyl), C(=O)-N(Rb)(Rc), C(=O)-R6, -N(Rb)(Rc), (C1-C4 alkyl)-N(Rb)(Rc), O-(C1-C4 alkyl), (C1-C4 alkyl)-O-(C1-C4 alkyl), C(=O)O-(C2C10 heterocycloalkyl), (C1-C4 alkyl)-C(=O)-R7 or (C2-C10 heterocycloalkyl)-C(=O)-Rs; Y é CH, N, O ou S {em que R4 é null when Y é O ou S}; R4 is H, C1-C4 alkyl, C3-C7 cycloalkyl, C2-C10 heterocycloalkyl, (C1-C4 alkyl)-(C2-C10 heterocycloalkyl), C6-C12 aryl, C2-C10 heteroaryl or C(=O) -R9, in which at least one H of C1-C4 alkyl, C2-C10 heterocycloalkyl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl) can be, each one,independently substituted with (C1-C4 alkyl)-O-(C1-C4 alkyl), C6-C12 aryl, C2-C10 heteroaryl, (C1-C4 alkyl)-(C2C10 heteroaryl), (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl) or C(=O)-(C1-C4 alkyl)-O-(C1-C4 alkyl); R5, R6, R7, R8, R9, R10 and R11 are each independently H, C1-C4 alkyl, (C1-C4 alkyl)-OH, (C1-C4 alkyl)-O-(C1-C4 alkyl), C2-C10 heterocycloalkyl, C6-C12 aryl, C2-C10 Petition 870260052856, dated 01 / 06 / 2026, page 57 / 102 3 / 47 heteroaryl, O-(C1-C4 alkyl), C3-C7 cycloalkyl or (C1-C4 alkyl)-N(Rb)(Rc), wherein at least one H of C6-C12 aryl or C2-C10 heteroaryl may each be independently substituted with C1-C4 alkyl, X or C1-C4 haloalkyl; Rb and Rc are each independently H, C1-C4 alkyl, C6-C12 aryl, C2-C10 heteroaryl, C3-C10 cycloalkyl,C2-C10 heterocycloalkyl, (C1-C4 alkyl)NH(C1-C4 alkyl), (C1-C4 alkyl)N(C1-C4 alkyl)2, (C1-C4 alkyl)-O-(C1-C4 alkyl), C(=O)-(C1-C4 alkyl), C(=O)-(C2-C10 heteroaryl), C(=O)-(C2-C10 heterocycloalkyl) or C(=O)-(C3-C10 cycloalkyl); X is a halogen atom; en is any integer selected from 0, 1, 2, and 3.

2. Compounds represented by chemical formula I or pharmaceutically acceptable salts thereof, according to claim 1, characterized in that, in the above chemical formula I, Zi to Z4 are each independently N or CRa, wherein Ra is H, X is C1-C4 alkyl or O-(C1-C4 alkyl) and Ra may differ from each other when CRa is 2 or more; or S; R1 is CX3 or CX2H; is C6-C12 arylene or C2-C10 heteroarylene, wherein C2-C10 heteroarylene may comprise at least one N;R2 and R3 are each independently H, X, C1-C4 haloalkyl, C6-C12 aryl, C2-C10 heterocycloalkyl, C2-C10 heterocycloalkenyl, N(Rb)(Rc) or C2-C10 heteroaryl, Petition 870260052856, dated 01 / 06 / 2026, page. 58 / 102 4 / 47 wherein at least one H of C6-C12 aryl, C2-C10 heteroaryl, C2-C10 heterocycloalkenyl or C2-C10 heterocycloalkyl can each be independently substituted with (C1-C4 alkyl)-(C2-C10 heteroaryl), (C1C4 alkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl), (C2-C10 heterocycloalkyl)-(C1-C4 haloalkyl), (C2-C10 heterocycloalkyl)-(C3-C10 cycloalkyl), (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl)-(C3-C10 halocycloalkyl), S(O2)-(C1-C4 alkyl), C(=O)-R6, O-(C1-C4 alkyl) or (C2-C10 heterocycloalkyl)-C(=O)-Rs; Y is CH, N, O or S {where R4 is zero when Y is O or S};R4 is C1-C4 alkyl, C2-C10 heterocycloalkyl, C2-C10 heteroaryl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl), in which at least one H of C1-C4 alkyl, C2-C10 heterocycloalkyl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl) can be, each one, independently substituted with C1-C4 alkyl, C1-C4 haloalkyl, O-(C1-C4 alkyl), -N(Rb)(Rc), C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, (C2-C10 heterocycloalkyl)-C(=O)-R10, S(O2)-(C1-C4 alkyl), C(=O)-R11, (C1-C4 alkyl)-O-(C1-C4 alkyl), C6-C12 aryl, (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl) or (C1-C4 alkyl)-(C2-C10 heteroaryl);R6, R8, R10 and R11 are each independently C1-C4 alkyl, (C1-C4 alkyl)-OH, (C1-C4 alkyl)-O-(C1-C4 alkyl), C2-C10 heterocycloalkyl, C6-C12 aryl, C2-C10 heteroaryl or O-(C1-C4 alkyl), wherein at least one H of C6-C12 aryl or C2-C10 heteroaryl may each be independently substituted with C1-C4 alkyl or C1-C4 haloalkyl; Rb and Rc are each independently H, C1-C4 alkyl or C(=O)-(C1-C4 alkyl); X is a halogen atom; en is any integer selected from 0, 1, 2, and 3.

3. Compounds represented by chemical formula I or pharmaceutically acceptable salts thereof, according to claim 1, characterized in that, in the above chemical formula I, C2-C10 heterocycloalkyl is w5 or wherein W1 to W6 are each independently N, NH, O, S or SO2, and each is independently an integer number of 1, 2 or 3.

4. Compounds represented by chemical formula I or pharmaceutically acceptable salts thereof, according to claim 1, the compounds represented by chemical formula I above being characterized by comprising compounds represented by the following chemical formula II: [Chemical Formula II] Petition 870260052856, dated 01 / 06 / 2026, page 60 / 102 6 / 47 r4 where, Z1 to Z4 are each independently N or CRa, where Ra is H, X, C1-C4 alkyl or O-(C1-C4 alkyl) and Ra may differ from each other when CRa is 2 or more; Z5 to Z8 are each independently CR2, CR3, CH or N, where Z5 to Z8 comprise CR2, CR3, CH and N, comprise CR2, CR3 and two Ns, or comprise CR2, CR3 and two CHs; K is O or S; R1 is CX3 or CX2H; R2 and R3 are each independently H, X, C1-C4 alkyl, C1-C4 haloalkyl, C6-C12 aryl, C2-C10 heteroaryl, C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, C2-C10 heterocycloalkenyl, N(Rb)(Rc), NH-(C1-C4 alkyl)-N(Rb)(Rc),NH-O-(C1-C4 alkyl) or NHC(=O)-R5, in which at least one H of C1-C4 alkyl, C6-C12 aryl, C2-C10 heteroaryl, C2-C10 heterocycloalkenyl or C2-C10 heterocycloalkyl can be, each one, independently substituted with X, C1-C4 alkyl, C1-C4 haloalkyl, C3-C10 cycloalkyl, C6-C12 aryl, C2-C10 heteroaryl, C2-C10 heterocycloalkyl, (C1-C4 alkyl)-(C2-C10 heteroaryl), (C1C4 alkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl), (C2-C10 heterocycloalkyl)-(C1-C4 haloalkyl), (C2-C10 Petition 870260052856, dated 01 / 06 / 2026, page 61 / 102 7 / 47 heterocycloalkyl)-(C3-C10 cycloalkyl), (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl)-(C3-C10 halocycloalkyl), (C1-C4 alkyl)-(C3-C10 cycloalkyl), S(O2)-(C1-C4 alkyl), C(=O)-N(Rb)(Rc), C(=O)-R6, -N(Rb)(Rc), (C1-C4 alkyl)-N(Rb)(Rc), O-(C1-C4 alkyl), (C1-C4 alkyl)-O-(C1-C4 alkyl), C(=O)O-(C2C10 heterocycloalkyl),(C1-C4 alkyl)-C(=O)-R7 or (C2-C10 heterocycloalkyl)-C(=O)-Rs; Y é CH, N, O ou S {em que R4 é null when Y é O ou S}; R4 is H, C1-C4 alkyl, C3-C7 cycloalkyl, C2-C10 heterocycloalkyl, (C1-C4 alkyl)-(C2-C10 heterocycloalkyl), C6-C12 aryl, C2-C10 heteroaryl or C(=O) -R9, in which at least one H of C1-C4 alkyl, C2-C10 heterocycloalkyl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl) can be, each one, independently substituted with X, C1-C4 alkyl, C1-C4 haloalkyl, O-(C1-C4 alkyl), -N(Rb)(Rc), C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, (C2-C10 heterocycloalkyl)-C(=O)-R10, S(O2)-(C1-C4 alkyl), C(=O)-R11, (C1-C4 alkyl)-O-(C1-C4 alkyl), C6-C12 aryl, C2-C10 heteroaryl, (C1-C4 alkyl)-(C2C10 heteroaryl), (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl) or C(=O)-(C1-C4 alkyl)-O-(C1-C4 alkyl); R5, R6, R7, Rs, R9, R10 and R11 são, each um, independently H, C1-C4 alkyl, (C1-C4 alkyl)-OH, (C1-C4 alkyl)-O-(C1-C4 alkyl), C2-C10 heterocycloalkyl,C6-C12 aryl, C2-C10 heteroaryl, O-(C1-C4 alkyl), C3-C7 cycloalkyl or (C1-C4 alkyl)-N(Rb)(Rc), wherein at least one H of C6-C12 aryl or C2-C10 heteroaryl may each be independently substituted with C1-C4 alkyl, X or C1-C4 haloalkyl; Petition 870260052856, dated 01 / 06 / 2026, p. 62 / 102 8 / 47 Rb and Rc are each independently H, C1-C4 alkyl, C6-C12 aryl, C2-C10 heteroaryl, C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, (C1-C4 alkyl)NH(C1-C4 alkyl), (C1-C4 alkyl)N(C1-C4 alkyl), (C1-C4 alkyl)-O-(C1-C4 alkyl), C(=O)-(C1-C4 alkyl), C(=O)-(C2-C10 heteroaryl), C(=O)-(C2-C10 heterocycloalkyl) or C(=O)-(C3-C10 cycloalkyl); X is a halogen atom; en is any integer selected from 0, 1, 2 and 3.

5. Compounds represented by chemical formula I or pharmaceutically acceptable salts thereof, according to claim 4, characterized in that Z1 to Z4 are each independently N or CRa, wherein Ra is H, X, C1-C4 alkyl or O-(C1-C4 alkyl) and Ra may differ from each other when CRa is 2 or more; Z5 to Z8 are each independently CR2, CR3, CH or N, wherein Z5 to Z8 comprise CR2, CR3, CH and N or comprise CR2, CR3 and two CHs (however, Ze is N when Z5 to Z8 comprise CR2, CR3, CH and N); K is O or S; R1 is CX3 or CX2H;R2 and R3 are each independently H, X, C1-C4 haloalkyl, C6-C12 aryl, C2-C10 heterocycloalkyl, C2-C10 heterocycloalkenyl, N(Rb)(Rc) or C2-C10 heteroaryl, wherein at least one H of C6-C12 aryl, C2-C10 heteroaryl, C2-C10 heterocycloalkenyl or C2-C10 heterocycloalkyl may each independently be substituted with X, C1-C4 alkyl, C1-C4 haloalkyl, C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, (C1-C4 alkyl)-(C2-C10 heteroaryl), (C1C4 alkyl)-(C2-C10 heterocycloalkyl), (C2-C10 Petition 870260052856, of 01 / 06 / 2026, p. 63 / 102 9 / 47 heterocycloalkyl)-(C1-C4 alkyl), (C2-C10 heterocycloalkyl)-(C1-C4 haloalkyl), (C2-C10 heterocycloalkyl)-(C3-C10 cycloalkyl), (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl)-(C3-C10 halocycloalkyl), S(O2)-(C1-C4 alkyl), C(=O)-R6, O-(C1-C4 alkyl) or (C2-C10 heterocycloalkyl)-C(=O)-Rs; Y is CH, N, O or S {where R4 is zero when Y is O or S};R4 is C1-C4 alkyl, C2-C10 heterocycloalkyl, C2-C10 heteroaryl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl), wherein at least one H of C1-C4 alkyl, C2-C10 heterocycloalkyl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl) may each be independently substituted with C1-C4 alkyl, C1-C4 haloalkyl, O-(C1-C4 alkyl), -N(Rb)(Rc), C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, (C2-C10 heterocycloalkyl)-C(=O)-R10, S(O2)-(C1-C4 alkyl), C(=O)-R11, (C1-C4 alkyl)-O-(C1-C4 alkyl), C6-C12 aryl, (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl) or (C1-C4 alkyl)-(C2-C10 heteroaryl); R6, R8, R10 and R11 are each independently C1-C4 alkyl, (C1-C4 alkyl)-OH, (C1-C4 alkyl)-O-(C1-C4 alkyl), C2-C10 heterocycloalkyl, C6-C12 aryl, C2-C10 heteroaryl or O-(C1-C4 alkyl), wherein at least one H of C6-C12 aryl or C2-C10 heteroaryl may each be independently substituted with C1-C4 alkyl or C1-C4 haloalkyl;Rb and Rc are each independently H, C1-C4 alkyl or C(=O)-(C1-C4 alkyl); X is a halogen atom; en is any integer selected from Petition 870260052856, dated 01 / 06 / 2026, page 64 / 102 10 / 47 0, 1, 2 and 3.; 6. Compounds represented by chemical formula I or pharmaceutically acceptable salts thereof, according to claim 4, characterized in that, in the above chemical formula II, Z1 to Z4 are each independently N or CRa, wherein Ra is H, X, C1-C4 alkyl or O-(C1-C4 alkyl) and Ra may differ from each other when CRa is 2 or more; Z5 to Z8 are each independently CR2, CR3, CH or N, wherein Z5 to Z8 comprise CR2, CR3, CH and N or comprise CR2, CR3 and two CHs (however, Z6 is N when Z5 to Z8 comprise CR2, CR3, CH and N); K is O or S; R1 is CX3 or CX2H;R2 and R3 are each independently H, X, C1-C4 haloalkyl, C6-C12 aryl, C2-C10 heterocycloalkyl, C2-C10 heterocycloalkenyl, N(Rb)(Rc) or C2-C10 heteroaryl, wherein at least one H of C6-C12 aryl, C2-C10 heteroaryl, C2-C10 heterocycloalkenyl or C2-C10 heterocycloalkyl may each be independently substituted with X, C1-C4 alkyl, C1-C4 haloalkyl, C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, (C1-C4 alkyl)-(C2-C10 heteroaryl), (C1C4 alkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl), (C2-C10 heterocycloalkyl)-(C1-C4 haloalkyl), (C2-C10 heterocycloalkyl)-(C3-C10 cycloalkyl), (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl)-(C3-C10 halocycloalkyl), S(O2)-(C1-C4 alkyl), C(=O)-R6, O-(C1-C4 alkyl) or (C2-C10 heterocycloalkyl)-C(=O)-R8; Petition 870260052856, of 06 / 01 / 2026, p. 65 / 102 11 / 47 Y is N, O or S {where R4 is null when Y is O or S};R4 is C1-C4 alkyl, C2-C10 heterocycloalkyl, C2-C10 heteroaryl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl), wherein at least one H of C1-C4 alkyl, C2-C10 heterocycloalkyl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl) may each be independently substituted with C1-C4 alkyl, C1-C4 haloalkyl, O-(C1-C4 alkyl), -N(Rb)(Rc), C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, (C2-C10 heterocycloalkyl)-C(=O)-R10, S(O2)-(C1-C4 alkyl), C(=O)-R11, (C1-C4 alkyl)-O-(C1-C4 alkyl), C6-C12 aryl, (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl) or (C1-C4 alkyl)-(C2-C10 heteroaryl); R6, Rs, R10 and R11 are each independently C1-C4 alkyl, (C1-C4 alkyl)-OH, (C1-C4 alkyl)-O-(C1-C4 alkyl), C2-C10 heterocycloalkyl, C6-C12 aryl, C2-C10 heteroaryl or O-(C1-C4 alkyl), wherein at least one H of C6-C12 aryl or C2-C10 heteroaryl may each be independently substituted with C1-C4 alkyl or C1-C4 haloalkyl;Rb and Rc are each independently H, C1-C4 alkyl, or C(=O)-(C1-C4 alkyl); X is a halogen atom; en is any integer selected from 0, 1, 2, and 3.

7. Compounds represented by chemical formula I or pharmaceutically acceptable salts thereof, according to claim 1, characterized in that, in the above chemical formula I, Z1 to Z4 are each independently N or CRa, wherein Ra is H or X, and Ra may differ from each other when CRa is 2 or more; K is O; Ri is CF3 or CF2H;phenylene or pyridinylene R2 and R3 only, each um, independently H, aryl, C2-C10 heteroaryl, C2-C10 heterocycloalkenyl or C2-C10 heterocycloalkyl may be, each, independently substituted with (C1C4 alkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl), (C2-C10 heterocycloalkyl)-(C1-C4 haloalkyl), (C2-C10 heterocycloalkyl)-(C3-C10 cycloalkyl), (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl), (C2-C10 heterocycloalkyl)-(C1-C4 alkyl)-(C3-C10 halocycloalkyl), S(O2)-(C1-C4 alkyl), C(=O)-Re, O-(C1-C4 alkyl) or (C2-C10 heterocycloalkyl)-C(=O)-Rs; Y is N, O or S {where R4 is null when Y is O or S};R4 is C1-C4 alkyl, C2-C10 heterocycloalkyl, C2-C10 heteroaryl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl), in which case except um H of C1-C4 alkyl, C2-C10 heterocycloalkyl or (C1-C4 alkyl)-(C2-C10 heterocycloalkyl) can be, each um, independently substituted with C1-C4 alkyl, C1-C4 haloalkyl, O-(C1-C4 alkyl), -N(Rb)(Rc), C3-C10 cycloalkyl, C2-C10 Petition 870260052856, dated 06 / 01 / 2026, p. 67 / 102 13 / 47 heterocycloalkyl, (C2-C10 heterocycloalkyl)-C(=O)-Rio, S(O2)-(C1-C4 alkyl), C(=O)-R11, (C1-C4 alkyl)-O-(C1-C4 alkyl), C6-C12 aryl, (C2-C10 heterocycloalkyl)-(C2-C10 heterocycloalkyl) or (C1-C4 alkyl)-(C2-C10 heteroaryl); R6 is C1-C4 alkyl, O-(C1-C4 alkyl) or (C1-C4 alkyl)OH; R8 is O-(C1-C4 alkyl); R10 is C1-C4 alkyl;R11 is C1-C4 alkyl, (C1-C4 alkyl)-OH, (C1-C4 alkyl)-O(C1-C4 alkyl), C2-C10 heterocycloalkyl, C6-C12 aryl, C2-C10 heteroaryl or O-(C1-C4 alkyl), wherein at least one H of C6-C12 aryl or C2-C10 heteroaryl may each be independently substituted with C1-C4 alkyl or C1-C4 haloalkyl; Rb and Rc are each independently H, C1-C4 alkyl or C(=O)-(C1-C4 alkyl); X is F, Cl or Br; en is 0 or 1.

8. Compounds represented by chemical formula I or pharmaceutically acceptable salts thereof, according to claim 1, the compounds being characterized by being selected from the group consisting of Petition 870260052856, dated 01 / 06 / 2026, page 68 / 102 14 / 47 Compound Structure 3 ATI A ° T ZCF2H -ZN~N \ 5 r CXI o °s / z Z— cix?.. 7 I / ο γ \ \ n'N N / 9 | T VCF2H Λ n'n N 1 11 nV a “ y-cF2H A nV CT Compound Structure 4 XXp A~z ° ) wz=< ^Ύ° o ΊΊ N> I 6 / Z~z ° ) z Λ / / z^° o ΙΌ I 8 A, 1 ü T ZCF2H X ... N 1 10 fy A ( ° Ύ Vcf2h / \ n'n \—N\ 12 I CM LL O / z Z. h / A ómi Petition 870260052856, of 01 / 06 / 2026, page 69 / 102 15 / 47 Compound Structure 13 T CN LL O 0¼ / zo O 15 AAv 0 IrCF^ N—' 17 ONN—' O 19 H 0 ,__, ιΑ ^znh 21 Q-çó.,..,, A 0 Ύ ACF?H nO n'n OJ Compound Structure 14 Atu / 0 Y 3—CF2H n~n 16 AÁv ya cf2h / \ n'N 0^ 18 XÁ. <a 20 ,£>N'N 22 %Av J. ° T ACF2H A nn / Petition 870260052856, of 06 / 01 / 2026, p. 70 / 102 16 / 47 Compound Structure 23 nn N 25 / θ II λ>—CF2H nn <N cr 27 QxX*YV 7 0 ll 4A-cf2h 29 ΞΕ CM O \ o &Va 31 Xxlo 0 J J / l-CFaH / A / N-N Composto Estrutura 24 W N'N <N cr 26 Qyyi nA / 0 Π Z>—CF2H nn rN o-^ 28 ζ^ΝΧίΝΊ νΑλ Uv°k J 0 Ύ / >-cf2h 30 z0Y Nn 32 A nn N 1 Petition 870260052856, of 06 / 01 / 2026, p. 71 / 102 17 / 47 Petition 870260052856, of 06 / 01 / 2026, p. 72 / 102 18 / 47 Compound Structure Compound Structure 43 J ° Y Ycf2h O N'N 47 °u.4 Az o ) OZ=\ ¥ O "Π ΓΌ _ 51 X CM OX / z zQ \ ,o Z~T jy Ογ 52 τ CM Ο 01 / 06 / 2026, p.74 / 102 20 / 47 Compound Structure Compound Structure 61 nA- __ / ° Ύ / Ycf2h o N—' O=( N—\ Q 62 F ΛΑ o _ / o Y YCF2H ΛΑ nY O cf3 63 I CN LL O \= oz O zr. À-Z ° ) wz=\ Ζγ° o NI 65 I CN O / z zfj Axi / c· o 6 6 F ΑΐΎΧ o nA, ΑΑ,ο _ / ο η Acf2H ΛΑ nn hA 0=( O- 67 Ô r OX\ ZO 6 ^ \ \ \ I CM LL O / z zQ ~f° Ay o Petição 870260052856, of 01 / 06 / 2026, pág 75 / 102 21 / 47 Compound Structure 69 OrX o γ o / )-CF2H n~n N—' / 71 Ay N- N' 07 N' N'... 75 XXl 0 A Ay,,, N~7O=í\ Compound Structure 70 A ZrA,, N—7 72 γρΛ o nA0 Χγ ^CF2Hn~n 74 X, ΛΛ nn 76 / Z z ° ) dz Ά / / z=\ z^ ti h^ ΊQ IQ 870260052856, of 01 / 06 / 2026, p. 76 / 102 22 / 47 Petition 870260052856, of 01 / 06 / 2026, p. 77 / 102 23 / 47 Compound Structure 87 Cl XX ΑΑγ 2H ΛΆ nn nA / 89 f3c Xy nA — / 0 Y ACF2H O N'N N—' / 91 F3C J 0 Y ACF2H / \ nn N—7 / 93 Y ACF2H / \ nn N—7 / 93 Y ACF2H N'N N—' / Compound Structure 88 Cl Ύί. fr· Alt-.· ύ 90 f3c Xxco J ° Y >- CF2H / \ n~NN—7 cr^ 92 f3c vÇÓUv __( θ II —cf2h Q Nn N—7 94 FX;úTo 4 ° Y ACF2H O N'N N—7 0^ Petition 870260052856, dated 01 / 06 / 2026, page 78 / 102 24 / 47 Petition 870260052856, dated 01 / 06 / 2026, page 79 / 102 25 / 47 Petition 870260052856, dated 01 / 06 / 2026, page Q N'N / 117 o < o >-CF,HQ N'N N—' / 119 Br QyAl o nA0 ΧΑγ ^CF2H ΛΑ nn N—' / 121 / VF νΑ'Ν'γρΧ. nA AzX-0 J 0 Ύ / >cf2h O N'N N—7 / Compound Structure 116 J ° Ύ Ycf2h o N'N / 118 7 '0 ^Srz>-CF2H o "'N / 120 N'N N—7 / 124 ° 0 ΟγΛ o \Ζ\Λ _ / o Y Vcf2h / \ n~n nA / Petition 870260052856, of 06 / 01 / 2026, p.82 / 102 28 / 47 Compost Structure Compost Structure 135 y' . \ Ί1 νΛο / —\ NY N— / 136 Yfy N—-- Υγ-Ν Y 71 / N Td YCF2H oA nY iZ / 137 YvAv» Y nY nY / 138 rY / 139 iY / 140 Ογν Y i ril \,YN^8O ycf2h r~\ nY hY / . 141 Br knx j 0 Y Ycf2h / \ n~n N—' / 142 F Y......-Q o nA. \Υ\γχ / ° T Ycf2h nY 143 Qnr\ 0 nAo ^_CFzHn'N 144 F ΜΥΎΥ o NÓ YaY / O, / ° Y Ycf2h nY 145 X CM O / zo Y° qZXi 146 ογ λΎ^ΤΝχ NÁ. AY\^OX J θ Υ Ycf2h Υ \ ν~ν νΥ / Petition 870260052856, dated 01 / 06 / 2026, p. 83 / 102 29 / 47 Petition 870260052856, dated 01 / 06 / 2026, p. 84 / 102 30 / 47 Petition 870260052856, dated 01 / 06 / 2026, p. 85 / 102 31 / 47 Composite Structure 171 o Υ X) Yz O ) z= / o ΓΌ x 173 X CM o O'S / zo \ .0 iL o 175 txçl· Λ-Ζ o ) o Z=< ΖγΟ O ΊΊ ΙΌ X 177 F ΓΑ / \ x VyVcf2H N^O NN 179 HCU ° \ 1 N—SsA.N-ζ LJ? ο < ) |L>~CF2H N / Compound Structure 172 Yz ° ) ^Ύ° o ΙΌ X 174 ΫΥ / OT Ycf2h / \ n'N l\Y °^\ 176 f3c %Xl , n-ϒ Yv°\ j-70 N= Y=N Y'\cf2 F\ rV nA„ XAx-a / 0 Y YCF2H n~n 180 f3c ° YY N— °y Petition 870260052856, dated 01 / 06 / 2026, p. 86 / 102 ) N) I 182 XnL / NY Ycf2h / Λ n~nz l\A °X 183 Ά.4 À^z ο ) Z=X zyb O Nd I 184 7=N Yc.. nA, \Av°.. _ / ο Y Acf2h °Ο ' \ γ n'N' ''^Ύ ^CFZH Ο N'N N—' O=^\ 186 OA / '-z^yz ° ) o Nd I 187 O Λ·α.ρ Xz O ) OZ=A Ζψ3 Ο Nd I 188 I CM o / z zQ A \ .9° O All ω 18- Petition 870260052856, dated 01 / 06 / 2026, p. <N LL O / z zQ \ O / / o 192 F xTXX o ΝΧχ Ύχ°, / 0 Y Ycf2h Γ\ nY o=sr 193 J 0 Y / Vcf2h / \ N-N N—' °Y 194 »+ο.Υ Yz ° ) ζ=λ ΖγΟ ο ΙΌ 195 X CM O í ο„Αό^ 11? UO 196 FSC vQÓÇo _J θ Υ cf2h Γ\ n~n Ν-7 0=s- 197 o YYo z U / Λ V Αι A Ίι «A Α / νΛ N^o ycF2H Ó N nA / 198 7 Ο Μ X 199 / z Xi X Cz Z=\ o N> T 200 τ CM Ο <0 / ζ ο \ ο Petition 870260052856, of 01 / 06 / 2026, pág. 88 / 102 34 / 47 Petition 870260052856, of 01 / 06 / 2026, pág. 89 / 102 35 / 47 Composite Structure Composite Structure 213 Cl CnX o / o γ / Ycf2h LA n~n rA / 214 Cl Cá o vUX / θ, __ / o γ >^cf2h / \ n~n 215 T CM O / z zQ .Ãxo o 216 Cl ΕρΧν Y Aí.5» N—7 O=s' O'' 217 EN—' / 218 X CM O °C Â <·Ύ cc L ° 219 X CM O °C / zo \ .0 Z —V ^Z^ Cr ^co 220 z CM O °C r 0 ^-ω=o II o 221 X CM O °cr ^Z^ Cr Ai ^z 222 X CM O / zo \ .oz~vi—4< ^z^ Cr \ ^ZZ 223 E r~Õ~\ir Yi / γA f vv γ ° N—' / 224 F aYiY'-i / ° U Á-CFzH nn Petition 870260052856, of 01 / 06 / 2026, pág. 90 / 102 36 / 47 Compound Structure 225 O II _ O=ω^ ^Ύ° ο ΤΊ ro I 227 nAo ^Y°y-CF2H n'N 229 X LL* o / z 20 \ .0 z\ Ã γγ Õ 231 A—CW ^A^A°A0I=2H— SA nn 233 Cl 0YY1 nA„ -- / 0 II ^—cf2H ON N-7 Composto Estrutura 226 F AWi nA„ AA. / ° u ACFzHn~n 228 Br AVa o oA ~Ά\ / Ο o Y Acf2h nn 230 Br A=an / ^AAa\°aCF2H S^A) NN 232 X CM o / z zQ Α .Ay 234 Cl A.....Λ o α\λ _ / ο γ Acf2h 0\ nA 0 Petição 870260052856, de 01 / 06 / 2026, pág. 91 / 102 37 / 47 Composto Estrutura Composto Estrutura 235 Cl o _ / o γ Acf2h A nY nA ( F / F FU, F 236 Cl Ya . nA, May _ / 0 Y Acf2h / \ nN ν—7 ( CF3 237 B0C'nYY_ íAo nn 238 Bo° МЖЫ / ХЪЪ o s-Λ \Y\,o, 0 Y Acf2h Nn 239 X Z. . АХЪ X / " AzA / :^Ύ° ο KJ ' X 240 F\ (z nY- Mv°xj ° Y Acf2h ΛΛ n'N nA < cf3 241 Ε ? Ο ^Υθ^-ΟΡ,Η Ο Ν F Ν-7 FA—JF—\ F 242 F\ f YA ο nA AAA a 0 Y / Acf2h O N-NffY F 243 ο Αχρ· Ο ) Ο ζ^\ ^Ύ° ο μ* I 244 aOya MeO2C <An‘ H A A / 0 Ύ ACFzH N-n Petição 870260052856, de 01 / 06 / 2026, pág. 92 / 102 38 / 47 Composto Estrutura Composto Estrutura 245 Xa / ÓLo.° Y Z-CFjH n'N 246 0 μ CF2H n'N 247 N=\ A / naa nA0 F2H NN 248 N^> F\ hn' / ΝΧ f2h r\ A N-, / 249 z^ —z \ O Ζγ ^Ύ° o N) I 250 X CM O € r-^4< ^Z^ d?zCa 251 Boc Aa o N s2',0 _ / OA / ZCF2H () N~N / 252 Boc ----, N \ íMa AAAAn-yY N—tm 0 Aí / · / 253 F\ CrkA Boc AA ° Ύ / >-cf2h O N'N N—'' / 254 Cl ç5 f Βοο'ΝΧ~γΑΝ / χ^Ν νΫ_ \A\<-o A, 0 Aí / · / 255 X CM O JX CCCa o'Z'z / o CO 256 __ F HN—f'AÁi nA„ Mv° Vof· ΓΛ nn N / 258 Oz a Xj NI Petition 870260052856, dated 01 / 06 / 2026, p. 94 / 102 40 / 47 Compost Structure Composite Structure 273 E NV X..O \ 274 0 oA / ' ..-OOA Acf2h nn 279 ΗΝΎχ 1 / F Υγλ o oA no OV / ^cf2h nn 280 , / Ύ° O nz 281 , / onz 282 ^=== / \ VN |f ,νΎ ^Y°>-cf2h Ó ύ 283 z N u °s . . . .284 F HNCJ -QrYA / o Y Ycf2h Nn 285 H nA VC» ! ° N ÁCF2H 286 IQ or fl Petition 870260052856, dated 01 / 06 / 2026, p. 95 / 102 41 / 47 Compound Structure Compound Structure 287 F nA„ sAx i 0 Ύ >-CF2H ΓΆ nn ^.NV oJ 288 - c J' OI 289 F HNY m ? Ύ jl n / 0 V n >-λ2 H X- N d 291 F nA, \ΑνΌχ < 1 >bd 292 F n=\ H,i^~€yN^b N-t0 b X— N u 293 F γΎ, aY N~N ογ-\_ / 294 F ^ΥΐH CF-γο / ο0 nA 295 2 y 2S A> I z^P o X 296 F ην-λ »A0 Yj-yCFiH z\ / \ nn oC^Nv__ / 297 Z IL Ü °s b° 298 Nx F\ θ^Γύυ^29 N-\bbY» N-\bbA0 A. Petition 870260052856, dated 01 / 06 / 2026, p. QrYi o nA, J ° Ύ >-CF2H C NN kA ύ 303 FV AVYb o / 0 Ύ >-cf2h nn 304 ν^ι / νΑν^ oA ° Ύ a-cf=h Nn 305 n~ob^τθ^ ΄ A^A^C) 0 Ύ / >-cf2h n~n 307 CO oo 3 oz 308 hnÀ / 5^ O-Λ A^A^C) 0 Ύ acf^h Nn 309 οΛ a^ac\ 0 H y-CFsH Nn 310 F hn n JA.75 ,-O / 0 Ύ Acf2h ONN 0 311 z IL* O 312 F n=\ V- ,Nb bb°^-CF2H bn~N 313 o ° 0 ^iT >-cf2h nn 314 ^^ΐΎι ob N—Αc3κ^- 316 F Mouth. N-Will vrt\. or 0 Ύ >-CF2H Nn Petition 870260052856, dated 01 / 06 / 2026, p. 97 / 102 43 / 47 Compound Structure Compound Structure 317 1 Φ oXj' 0 Z'V° o X 318 a ? Ύ 1 ο γ >-cf2h nn 319 O ___Λ IL---C / VO 0 / 320 YY, N-^. / OY cf2h ύ N'N 321 AY, N-^. / 0 Y y-CF2H ύ N'N 322 °A / τ' Y o *1 323 YÜÂ N λ 1 II Ί HA Yv-O A YF'H 0 324 F x=m~Nv NY N \ A \ Y / ΥN Άύ ί^Υ1-Ί A ° Y Y-cf2h 0 N~ 325 F z--N ' z--. 0=3 \ '--- / \ X vfl 1 A Ύ YCF2H \ \ nN CT 326 F O-Jy νΑλ AAx^O / 0 Y Ycf2h ) nn —N \ 327 AZ. o >^v Λ—zo ) wz=\ ^Ύ° o N) X 328 F OyS / =0^° ^Y°Ycf2h O ~N 329 0 aXr .0 ^Ύ° o Ni 1 330 νΛλ x^x^Ov / 0 Nn\0 z=ε32h YCF2H Nn 332 0 Y YCF2H Nn Petition 870260052856, dated 01 / 06 / 2026, p.98 / 102 44 / 47 Compound Structure Compound Structure 333 ΑχΥ ο γ Mcf2h N'N 334 F ~~n / A_2A, oA„ AXa OY Mcf2h Nn 335 \ F\ Z^N o MCA2° NV / Ύ = ΞΕ 337 b°c~OaaJA °A ^y0>-CF2H nn 338 nOnyn~vX ΝΑγΝ^Ν ok 0 Y >-cf2h nn 339 N~s F\ ”_ / NY )=- n=ALAny% ot z—ο3 / ο 2. u-Hf) 7ZX° zi O Oo 341 bkO j\ A --' N—Z \ V / \.N. IJ-k ,NA> Ύ y-CF2H Me nn 342 ΜθγΑι-γ / ΝΑ V, X ü O ,Ν^Ο Ύ >-CF2H Me nn 343 2 0 ' ηύ o I 344 Boc-0 _·_AN_—, F Ύ >-cf2h Nn 345 I 0 zA / / J oV V o η I 346 —NZ F\ ^Χχϊΐ o ° 0 ^ιΓ Mcf2h Nn 347 ^Qr~A o U y-cf2h nn 348 CF—49 / Ο N2 fa ε ΑΛ-γ ok, Uvi o Y >-cf2h Nn 350 °0>- / 5 Ns F\ _ / N~Y V-zA °A> ^Y°>-CF2H nn Petition 870260052856, dated 01 / 06 / 2026, p. 99 / 102 45 / 47 Compound Structure Compound Structure 351 Z~-NZ~~\, N—-.F\ CF3 \__yt—à· ° 0 ^^ιΓ°Χ-ορ2η nn 352 CO on Hu / ° o N ' z 353 N=\ __ J 1 T Ί s-Ά \A / o, 0 ΰ / >-CF2Hn-N 354 N=a XN \ । || 1 T sA ' 0 Ύ / >-CF'Hn-N 355 ' 0 uH 356 cf'X'n3t o Y >-CF2H Nn 357 xuArp„ SÁ \A\ / O ο AXu. '-sX—s.-O 0 « >-CF2H Nn 364 F \ ) °A_ Av°.

9. Pharmaceutical composition characterized by comprising compounds represented by chemical formula I as defined in any one of claims 1 to 8 or pharmaceutically acceptable salts thereof as an effective component.

10. Pharmaceutical composition, according to claim 9, said pharmaceutical composition being characterized in that it is used to prevent or treat diseases related to histone deacetylase 6 activity, wherein said diseases related to histone deacetylase 6 activity are at least one selected from the group consisting of infectious diseases, neoplasms, endocrinopathy, nutritional and metabolic diseases, mental and behavioral disorders, neurological diseases, ocular and adnexal diseases, respiratory diseases, digestive diseases, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue diseases or teratosis, deformities and chromosomal aberration.

11. Use of the pharmaceutical composition, according to claim 9, said pharmaceutical composition being characterized by being used in the preparation of a medicament to prevent or treat diseases related to histone deacetylase 6 activity, wherein said diseases related to histone deacetylase 6 activity are at least one selected from the group consisting of infectious diseases, neoplasms, endocrinopathy, nutritional and metabolic diseases, mental and behavioral disorders, neurological diseases, ocular and adnexal diseases, respiratory diseases, digestive diseases, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue diseases or teratosis, deformities and chromosomal aberration.

12. Use of the compounds represented by chemical formula I as defined in any one of claims 1 to 8 or pharmaceutically acceptable salts thereof, characterized in that they are in the preparation of a medicament for preventing or treating diseases related to histone deacetylase 6 activity, wherein said diseases related to histone deacetylase 6 activity are at least one selected from the group consisting of infectious diseases, neoplasms, endocrinopathy, nutritional and metabolic diseases, mental and behavioral disorders, neurological diseases, ocular and adnexal diseases, respiratory diseases, digestive diseases, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue diseases or teratosis, deformities and chromosomal aberration.