Seven-membered ring compound and pharmaceutical use therefor

A compound, or a salt or solvate thereof having the formula (I):

• wherein, Ar indicates (1) a C6 to C14 aromatic hydrocarbon group, (2) a 5- to 8-membered aromatic heterocyclic group including 1 to 4 hetero atoms selected from a nitrogen atom, sulfur atom, and oxygen atom, other than a carbon atom, or (3) a bicyclic or tricyclic aromatic group formed by condensation of the above aromatic heterocyclic group and a C6 to C14 aromatic hydrocarbon ring,
• where the above groups (1) to (3) of Ar are unsubstituted or substituted with 1 to 5 groups selected from:
• (i) a halogen atom,
• (ii) nitro,
• (iii) cyano,
• (iv) C1 to C6 alkyl unsubstituted, or substituted with 1 to 3 halogen atoms,
• (v) C2 to C6 alkenyl unsubstituted, or substituted with 1 to 3 halogen atoms,
• (vi) C2 to C6 alkynyl unsubstituted, or substituted with 1 to 3 halogen atoms,
• (vii) C3 to C6 cycloalkyl,
• (viii) hydroxyl,
• (ix) C1 to C6 alkoxy unsubstituted, or substituted with 1 to 3 groups selected from a halogen atom, mono- or di-C1 to C6 alkylamino, C1 to C6 alkoxy, mono- or di-C1 to C6 alkylcarbamoyl, mono- or di-C7 to C16 aralkylcarbamoyl, mono- or di-C1 to C10 heteroaryl-C1 to C6 alkylcarbamoyl, carboxyl, and C1 to C6 alkoxycarbonyl, or substituted with 1 to 13 deuterium atom
• (x) C1 to C5 alkylenedioxy,
• (xi) C1 to C6 alkylthio unsubstituted, or substituted with 1 to 3 groups selected from a halogen atom, mono- or di-C1 to C6 alkylamino, C1 to C6 alkoxy, mono- or di-C1 to C6 alkylcarbamoyl, mono- or di-C7 to C16 aralkylcarbamoyl, mono- or di-C1 to C10 heteroaryl-C1 to C6 alkylcarbamoyl, carboxyl, and C1 to C6 alkoxycarbonyl, or substituted with 1 to 13 deuterium atom
• (xii) amino,
• (xiii) mono-C1 to C6 alkylamino,
• (xiv) di-C1 to C6 alkylamino,
• (xv) 5- to 6-membered cyclic amino,
• (xvi) C1 to C6 alkylcarbonyl,
• (xvii) carboxyl,
• (xviii) C1 to C6 alkoxycarbonyl,
• (xix) carbamoyl,
• (xx) thiocarbamoyl,
• (xxi) mono-C1 to C6 alkylcarbamoyl,
• (xxii) di-C1 to C6 alkylcarbamoyl,
• (xxiii) 5- to 6-membered cyclic aminocarbonyl,
• (xxiv) sulfo,
• (xxv) C1 to C6 alkylsulfonyl,
• (xxvi) C1 to C6 alkoxycarbonylamino,
• (xxvii) C1 to C6 alkylcarbonylamino,
• (xxviii) mono- or di-C1 to C6 alkylaminocarbonylamino,
• (xxix) aminosulfonyl, and
• (xxx) mono- or di-C1 to C6 alkylaminosulfonyl, or
• substituted with (xxxi) 1 to 9 deuterium atoms,
• X indicates (1) a connecting bond, (2) linear or branched C1 to C6 alkylene unsubstituted, or substituted with 1 to 12 deuterium atoms, (3) an oxygen atom, (4) NR3, where R3 indicates a hydrogen atom or a C1 to C6 alkyl group, or (5) —S(O)m—, where m indicates an integer of 0 to 2, Z indicates (1) a connecting bond or (2) CR4R5, where R4 and R5 are, independently,
• (A) a hydrogen atom,
• (B) a deuterium atom,
• (C) C1 to C6 alkyl unsubstituted, or substituted with 1 to 5 groups selected from the group consisting of (i) carboxyl, (ii) C1 to C6 alkoxycarbonyl, (iii) phenyl, (iv) hydroxyl, (v) C1 to C6 alkoxy, (vi) a halogen atom, and (vii) C3 to C6 cycloalkyl, or substituted with (viii) 1 to 13 deuterium atoms,
• (D) C3 to C6 cycloalkyl unsubstituted, or substituted with 1 to 5 groups selected from the group consisting of (i) a halogen atom and (ii) an alkyl group unsubstituted, or substituted with 1 to 3 halogen atoms or unsubstituted, or substituted, with (iii) 1 to 11 deuterium atoms,
• (E) COOR6 where R6 indicates a hydrogen atom or C1 to C6 alkyl, or
• (F) CONR7R8 where R7 and R8 are, independently,
• (a) hydrogen atom,
• (b) C1 to C6 alkyl unsubstituted, or substituted with 1 to 3 groups selected from the group consisting of (i) a halogen atom, (ii) C3 to C6 cycloalkyl, (iii) carboxyl, (iv) C1 to C6 alkoxycarbonyl, (v) C1 to C6 alkylcarbonyl, (vi) carbamoyl, (vii) mono-C1 to C6 alkylcarbamoyl, (viii) di-C1 to C6 alkylcarbamoyl, (ix) C6 to C12 aryl, and (x) C1 to C10 heteroaryl,
• (c) C6 to C14 aromatic hydrocarbon group,
• (d) a 5- to 8-membered aromatic heterocyclic group including 1 to 4 hetero atoms selected from a nitrogen atom, sulfur atom, and oxygen atom, other than a carbon atom, or
• (e) a bicyclic or tricyclic aromatic group formed by condensation of the above aromatic heterocyclic group and a C6 to C14 aromatic hydrocarbon ring,
• where each of the groups (c) to (e) is unsubstituted, or substituted with 1 to 5 groups selected from the group consisting of (i) a halogen atom, (ii) nitro, (iii) cyano, (iv) C1 to C6 alkyl unsubstituted, or substituted with 1 to 3 halogen atoms, (v) C2 to C6 alkenyl unsubstituted, or substituted with 1 to 3 halogen atoms, (vi) C2 to C6 alkynyl unsubstituted, or substituted with 1 to 3 halogen atoms, (vii) C3 to C6 cycloalkyl, (viii) hydroxyl, (ix) C1 to C6 alkoxy unsubstituted, or substituted with 1 to 3 halogen atoms, (x) C1 to C5 alkylenedioxy, (xi) C1 to C6 alkylthio unsubstituted, or substituted with 1 to 3 halogen atoms, (xii) amino, (xiii) mono-C1 to C6 alkylamino, (xiv) di-C1 to C6 alkylamino, (xv) 5- to 6-membered cyclic amino, (xvi) C1 to C6 alkylcarbonyl, (xvii) carboxyl, (xviii) C1 to C6 alkoxycarbonyl, (xix) carbamoyl, (xx) thiocarbamoyl, (xxi) mono-C1 to C6 alkylcarbamoyl, (xxii) di-C1 to C6 alkylcarbamoyl, (xxiii) C6 to C10 arylcarbamoyl, (xxiv) C1 to C10 heteroarylcarbamoyl, (xxv) sulfo, (xxvi) C1 to C6 alkylsulfonyl, (xxvii) aminosulfonyl, and (xxviii) mono- or di-C1 to C6 alkylaminosulfonylamino, or substituted with (xxix) 1 to 9 deuterium atoms,
• W indicates (1) a hydrogen atom, (2) a C6 to C14 aromatic hydrocarbon group, (3) a 5- to 8-membered aromatic heterocyclic group including 1 to 4 hetero atoms selected from a nitrogen atom, a sulfur atom, and an oxygen atom, other than a carbon atom, (4) a bicyclic or tricyclic aromatic group formed by condensation of the above aromatic heterocyclic group and a C6 to C14 aromatic hydrocarbon ring, or (5) deuterium atom,
• where each of the groups (2) to (4) of the above W is unsubstituted, or substituted with 1 to 5 groups selected from the group consisting of (i) a halogen atom, (ii) nitro, (iii) cyano, (iv) C1 to C6 alkyl unsubstituted, or substituted with 1 to 3 groups selected from a halogen atom, amino, C1 to C6 alkoxycarbonyl, C1 to C6 alkoxycarbonylamino, and carboxyl, (v) C2 to C6 alkenyl unsubstituted, or substituted with 1 to 3 halogen atoms, (vi) C2 to C6 alkynyl unsubstituted, or substituted with 1 to 3 halogen atoms, (vii) C3 to C6 cycloalkyl, (viii) hydroxyl, (ix) C1 to C6 alkoxy unsubstituted, or substituted with 1 to 3 groups selected from a halogen atom, hydroxyl, C1 to C6 alkoxy, amino and mono- or di-C1 to C6 alkylamino, (x) C1 to C5 alkylenedioxy, (xi) C1 to C6 alkylthio unsubstituted, or substituted with 1 to 3 groups selected from a halogen atom, hydroxyl, C1 to C6 alkoxy, amino, and mono- or di-C1 to C6 alkylamino, (xii) amino, (xiii) mono-C1 to C6 alkylamino, (xiv) di-C1 to C6 alkylamino, (xv) 5- to 6-membered cyclic amino, (xvi) C1 to C6 alkyl-carbonyl, (xvii) carboxyl, (xviii) C1 to C6 alkoxycarbonyl unsubstituted, or substituted with a halogen atom, (xix) C7 to C16 arakyloxycarbonyl unsubstituted, or substituted with a halogen atom, (xx) carbamoyl, (xxi) mono-C1 to C6 alkylcarbamoyl unsubstituted, or substituted with 1 to 3 groups which are selected from a halogen atom, hydroxyl, carboxyl, C1 to C6 alkoxy, amino, and mono- or di-C1 to C6 alkylamino, (xxii) di-C1 to C6 alkylcarbamoyl unsubstituted, or substituted with hydroxyl, (xxiii) 5- to 6-membered cyclic aminocarbonyl unsubstituted, or substituted with C1 to C6 alkoxycarbonyl, (xxiv) C6 to C10 arylcarbamoyl, (xxv) C1 to C10 heteroarylcarbamoyl, (xxvi) C7 to C16 aralkylcarbamoyl, (xxvii) C1 to C10 heteroaryl-C1 to C6 alkylcarbamoyl, (xxviii) N—C1 to C6 alkyl-N—C6 to C12 arylcarbamoyl, (xxix) C3 to C6 cycloalkylcarbamoyl, (xxx) sulfo, (xxxi) C1 to C6 alkylsulfonyl, (xxxii) C1 to C6 alkylsulfonylamino, (xxxiii) C6 to C12 arylsulfonylamino unsubstituted, or substituted with C1 to C6 alkyl, (xxxiv) C1 to C10 heteroarylsulfonylamino, (xxxv) C1 to C6 alkoxycarbonylamino, (xxxvi) C1 to C6 alkylcarbonylamino, (xxxvii) mono- or di-C1 to C6 alkylaminocarbonylamino, (xxxviii) C6 to C12 aryl, (xxxix) C1 to C10 heteroaryl, (xl) C6 to C10 aryloxy, (xli) C1 to C10 heteroaryloxy, (xlii) C7 to C16 arakyloxy, (xliii) C1 to C10 heteroaryl-C1 to C6 alkyloxy, (xliv) aminosulfonyl, (xlv) mono- or di-C1 to C6 alkylaminosulfonyl, (xlvi) C7 to C16 aralkyloxycarbamoyl, and (xlvii) C1 to C10 heteroaryl-C1 to C6 alkyloxycarbamoyl, or substituted with (xlviii) 1 to 9 deuterium atoms,
• R1 indicates
• (1) a hydrogen atom,
• (2) C1 to C6 alkyl unsubstituted, or substituted with 1 to 3 of (i) a halogen atom or (ii) C3 to C6 cycloalkyl or substituted with (iii) 1 to 13 deuterium atoms,
• (3) C2 to C6 alkenyl unsubstituted, or substituted with 1 to 3 of (i) a halogen atom or (ii) C3 to C6 cycloalkyl or substituted with (iii) 1 to 11 deuterium atoms,
• (4) C2 to C6 alkynyl unsubstituted, or substituted with 1 to 3 of (i) a halogen atom or (ii) C3 to C6 cycloalkyl, or substituted with (iii) 1 to 9 deuterium atoms, or
• (5) C3 to C6 cycloalkyl unsubstituted, or substituted with 1 to 3 of (i) a halogen atom or (ii) C3 to C6 cycloalkyl, or substituted with (iii) 1 to 11 deuterium atoms,
• R2 indicates (1) OR9 or (2) NR10R11
• where, R9, R10, and R11 independently indicate
• (A) a hydrogen atom,
• (B) C1 to C6 alkyl,
• (C)C2 to C6 alkenyl,
• (D) C2 to C6 alkynyl,
• (E) C3 to C6 cycloalkyl
• (F) C6 to C14 aromatic hydrocarbon group,
• (G) a 5- to 8-membered aromatic heterocyclic group including 1 to 4 hetero atoms selected from a nitrogen atom, sulfur atom, and oxygen atom, other than a carbon atom, or
• (H) a bicyclic or tricyclic aromatic group formed by condensation of the above aromatic heterocyclic group and a C6 to C14 aromatic hydrocarbon ring,
• where each of the groups of the above (B) to (E) is unsubstituted, or substituted with 1 to 3 groups selected from the group consisting of (i) a halogen atom, (ii) C3 to C6 cycloalkyl, (iii) hydroxyl, (iv) C1 to C6 alkoxy unsubstituted, or substituted with 1 to 3 halogen atoms, (v) amino, (vi) mono-C1 to C6 alkylamino, (vii) di-C1 to C6 alkylamino, (viii) 5- to 6-membered cyclic amino, (ix) carboxyl, (x) C1 to C6 alkoxycarbonyl, (xi) C1 to C6 alkylcarbonyl, (xii) carbamoyl, (xiii) mono-C1 to C6 alkylcarbamoyl, (xiv) di-C1 to C6 alkylcarbamoyl, (XV) C6 to C12 aryl, and (xvi) C1 to C10 heteroaryl, or substituted with (xvii) 1 to 13 deuterium atoms,
• further, each of the groups of the above (F) to (H) unsubstituted, or substituted with 1 to 5 groups which are selected from the group consisting of (i) a halogen atom, (ii) nitro, (iii) cyano, (iv) C1 to C6 alkyl unsubstituted, or substituted with 1 to 3 halogen atoms, (v) C3 to C6 cycloalkyl unsubstituted, or substituted with 1 to 3 halogen atoms, (vi) hydroxyl, (vii) C1 to C6 alkoxy unsubstituted, or substituted with 1 to 3 halogen atoms, (viii) amino, (ix) mono-C1 to C6 alkylamino, (x) di-C1 to C6 alkylamino, (xi) 5- to 6-membered cyclic amino, (xii) C1 to C6 alkylcarbonyl, (xiii) carboxyl, (xiv) C1 to C6 alkoxycarbonyl, (xv) carbamoyl, (xvi) mono-C1 to C6 alkylcarbamoyl, (xvii) di-C1 to C6 alkylcarbamoyl, (xviii) C1 to C6 alkylsulfonyl, (xix) aminosulfonyl, and (xx) mono- or di-C1 to C6 alkylaminosulfonyl, or substituted with (xxi) 1 to 9 deuterium atoms, or
• R1 and R2 may form 5- or 6-member heterocyclic ring together with the atoms they are bonded with,
• where the above 5- or 6-member heterocyclic ring is unsubstituted, or substituted with 1 to 3 groups selected from
• (A) a halogen atom
• (B) oxo
• (C) hydroxyl
• (D) C1 to C6 alkyl,
• (E) C2 to C6 alkenyl,
• (F) C2 to C6 alkynyl,
• (G) C3 to C6 cycloalkyl
• (H)C6 to C14 aromatic hydrocarbon group,
• (I) 5- to 8-membered aromatic heterocyclic group including 1 to 4 hetero atoms selected from a nitrogen atom, sulfur atom, and oxygen atom, other than a carbon atom, and
• (J) a bicyclic or tricyclic aromatic group formed by condensation of the above aromatic heterocyclic group and a C6 to C14 aromatic hydrocarbon ring, or substituted with
• (K) 1 to 6 deuterium atoms,
• where each of the groups of the above (D) to (G) is unsubstituted, or substituted with 1 to 3 groups selected from the group consisting of (i) a halogen atom, (ii) C3 to C6 cycloalkyl, (iii) hydroxyl, (iv) C1 to C6 alkoxy unsubstituted, or substituted with 1 to 3 halogen atoms, (v) amino, (vi) mono-C1 to C6 alkylamino, (vii) di-C1 to C6 alkylamino, (viii) 5- to 6-membered cyclic amino, (ix) carboxyl, (x) C1 to C6 alkoxycarbonyl, (xi) C1 to C6 alkyl-carbonyl, (xii) carbamoyl, (xiii) mono-C1 to C6 alkylcarbamoyl, (xiv) di-C1 to C6 alkylcarbamoyl, (xv) C6 to C12 aryl and (xvi) C1 to C10 heteroaryl, or substituted with (xvii) 1 to 13 deuterium atoms,
• each of the groups of the above (H) to (J) is unsubstituted, or substituted with 1 to 5 groups which are selected from the group consisting of (i) a halogen atom, (ii) nitro, (iii) cyano, (iv) C1 to C6 alkyl unsubstituted, or substituted with 1 to 3 halogen atoms, (v) C3 to C6 cycloalkyl unsubstituted, or substituted with 1 to 3 halogen atoms, (vi) hydroxyl, (vii) C1 to C6 alkoxy unsubstituted, or substituted with 1 to 3 halogen atoms, (viii) amino, (ix) mono-C1 to C6 alkylamino, (x) di-C1 to C6 alkylamino, (xi) 5- to 6-membered cyclic amino, (xii) C1 to C6 alkylcarbonyl, (xiii) carboxyl, (xiv) C1 to C6 alkoxycarbonyl, (xv) carbamoyl, (xvi) mono-C1 to C6 alkylcarbamoyl, (xvii) di-C1 to C6 alkylcarbamoyl, (xviii) C1 to C6 alkylsulfonyl, (xix) aminosulfonyl, and (xx) mono- or di-C1 to C6 alkylaminosulfonyl, or substituted with (xxi) 1 to 9 deuterium atoms.