Piperazine indazole glucocorticoid receptor antagonists

Abstract

The present disclosure provides piperazine-substituted fused azadecalin compounds of formula J, formula I, formula Ia, formula Ib, formula Ib-1, formula Ib-2, formula Ic, and formula Id for use in pharmaceutical formulations and for modulating the glucocorticoid receptor.

Claims

1. A compound of formula J, 【Chemistry 1】 During the ceremony, R １ is heterocycloalkyl having 3 to 12 ring members and 1 to 4 heteroatoms each being N, O, or S, phenyl, or heteroaryl having 5 to 10 ring members and 1 to 5 heteroatoms each being N, O, or S, each independently comprising 0 to 5 R １ａ is substituted with a group, Each R １ａ became independent and C １－６ Alkyl, C １－６ Alkoxy, C １－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -OH, oxo, -CN, -C(O)N(R １ｂ ) (R １ｃ ), C ３－１０ cycloalkyl or heterocycloalkyl having 3 to 12 ring members and 1 to 4 heteroatoms, each of which is N, O, or S; Each R １ｂ and R １ｃ are independently hydrogen, C １－６ alkyl, or a 3- to 8-membered heterocycloalkyl having 1 to 3 heteroatoms, each independently N, O, or S; A １ , A ２ , A ３ , and A ４ Each independently represents CR ２ - or =N-, Each R ２ are independently hydrogen, C １－６ Alkyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, halogen, C １－６ Haloalkyl, C １－６ haloalkoxy, hydroxy, or -CN; L ２ is -C(O)-, -C(O)O-, -C(O)N(R ３ ) -, -S(O) ２ - or -S(O) ２ N (R ３ ) - and R ３ is hydrogen or C １－６ is alkyl, R ４ But, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, —O—C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl; wherein each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms which are each independently N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms which are each independently N, O, or S; The cycloalkyl, the heterocycloalkyl, the aryl, and the heteroaryl each independently represent 0 to 5 R ４ａ is substituted with a group, Alternatively, R ３ and R ４ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 additional heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ４ａ became independent and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -CN, -OH, oxo, -C(O)R ４ｂ , -C(O)OR ４ｂ , -OC(O)R ４ｂ , -OC(O)OR ４ｂ , -C(O)N(R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) C(O)R ４ｃ , -OC(O)N(R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) C(O)OR ４ｃ , -S(O) ２ R ４ｂ , -S(O) ２ N (R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) S (O) ２ R ４ｃ , C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, —O—C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ４ｂ and R ４ｃ is hydrogen or C １－６ is alkyl, R ５ But, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C １－６ Alkyl-OR ５ａ , -C(O)R ５ａ , C １－６ Alkyl-C(O)R ５ａ , -C(O)OR ５ａ , -C(O)N(R ５ａ ) (R ５ｂ ), -S(O) ２ R ５ａ , -S(O) ２ N (R ５ａ ) (R ５ｂ ), C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl; wherein each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms which are each independently N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms which are each independently N, O, or S; Each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents 0 to 4 R ５ｃ is substituted with a group, Each R ５ａ and R ５ｂ are independently hydrogen, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, hydroxy, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C １－６ Haloalkoxy, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently has 0 to 4 R ５ｄ is substituted with a group, Alternatively, R ５ａ and R ５ｂ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 additional heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｃ became independent and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -CN, oxo, -OH, -C(O)R ５ｃ１ , -C(O)OR ５ｃ１ , -OC(O)R ５ｃ１ , -OC(O)OR ５ｃ１ , -C(O)N(R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) C(O)R ５ｃ２ , -OC(O)N(R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) C(O)OR ５ｃ２ , -S(O) ２ R ５ｃ１ , -S(O) ２ N (R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) S (O) ２ R ５ｃ２ , C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each heterocycloalkyl and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｃ１ and R ５ｃ２ are independently hydrogen, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each heterocycloalkyl and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Alternatively, R ５ｃ１ and R ５ｃ２ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｄ became independent and C １－６ is alkyl or halogen; Each R ６ are independently hydrogen, C １－６ Alkyl, halogen, C １－６ haloalkyl, or oxo; subscript m is 0, 1, 2, 3, 4, or 5; A compound, or a pharma- ceutically acceptable salt thereof, wherein the subscript n is 1 or 2.

2. Formula I 【Chemistry 2】 The structure is R １ is heterocycloalkyl having 3 to 12 ring members and 1 to 4 heteroatoms each being N, O, or S, phenyl, or heteroaryl having 5 to 10 ring members and 1 to 5 heteroatoms each being N, O, or S, each independently comprising 0 to 5 R １ａ is substituted with a group, Each R １ａ became independent and C １－６ Alkyl, C １－６ Alkoxy, C １－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -OH, oxo, -CN, -C(O)N(R １ｂ ) (R １ｃ ), C ３－１０ cycloalkyl or heterocycloalkyl having 3 to 12 ring members and 1 to 4 heteroatoms, each of which is N, O, or S; Each R １ｂ and R １ｃ are independently hydrogen, C １－６ alkyl, or a 3- to 8-membered heterocycloalkyl having 1 to 3 heteroatoms, each independently N, O, or S; A １ , A ２ , A ３ , and A ４ Each independently represents CR ２ - or =N-, Each R ２ are independently hydrogen, C １－６ Alkyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, halogen, C １－６ Haloalkyl, C １－６ haloalkoxy, hydroxy, or -CN; L ２ is -C(O)-, -C(O)O-, -C(O)N(R ３ ) -, -S(O) ２ - or -S(O) ２ N (R ３ ) - and R ３ is hydrogen or C １－６ is alkyl, R ４ But, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, —O—C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl; wherein each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms which are each independently N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms which are each independently N, O, or S; The cycloalkyl, the heterocycloalkyl, the aryl, and the heteroaryl each independently represent 0 to 5 R ４ａ is substituted with a group, Alternatively, R ３ and R ４ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 additional heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ４ａ became independent and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -CN, -OH, oxo, -C(O)R ４ｂ , -C(O)OR ４ｂ , -OC(O)R ４ｂ , -OC(O)OR ４ｂ , -C(O)N(R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) C(O)R ４ｃ , -OC(O)N(R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) C(O)OR ４ｃ , -S(O) ２ R ４ｂ , -S(O) ２ N (R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) S (O) ２ R ４ｃ , C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, —O—C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ４ｂ and R ４ｃ is hydrogen or C １－６ is alkyl, R ５ But, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C １－６ Alkyl-OR ５ａ , -C(O)R ５ａ , C １－６ Alkyl-C(O)R ５ａ , -C(O)OR ５ａ , -C(O)N(R ５ａ ) (R ５ｂ ), -S(O) ２ R ５ａ , -S(O) ２ N (R ５ａ ) (R ５ｂ ), C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl; wherein each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms which are each independently N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms which are each independently N, O, or S; Each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents 0 to 4 R ５ｃ is substituted with a group, Each R ５ａ and R ５ｂ are independently hydrogen, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, hydroxy, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C １－６ Haloalkoxy, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently has 0 to 4 R ５ｄ is substituted with a group, Alternatively, R ５ａ and R ５ｂ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 additional heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｃ became independent and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -CN, oxo, -OH, -C(O)R ５ｃ１ , -C(O)OR ５ｃ１ , -OC(O)R ５ｃ１ , -OC(O)OR ５ｃ１ , -C(O)N(R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) C(O)R ５ｃ２ , -OC(O)N(R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) C(O)OR ５ｃ２ , -S(O) ２ R ５ｃ１ , -S(O) ２ N (R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) S (O) ２ R ５ｃ２ , C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each heterocycloalkyl and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｃ１ and R ５ｃ２ are independently hydrogen, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each heterocycloalkyl and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Alternatively, R ５ｃ１ and R ５ｃ２ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｄ became independent and C １－６ is alkyl or halogen; Each R ６ are independently hydrogen, C １－６ Alkyl, halogen, C １－６ haloalkyl, or oxo; 2. The compound of claim 1, wherein subscript m is 0, 1, 2, 3, 4, or 5, or a pharma- ceutically acceptable salt thereof.

3. R １ is heterocycloalkyl having 3 to 12 ring members and 1 to 4 heteroatoms each being N, O, or S, phenyl, or heteroaryl having 5 to 10 ring members and 1 to 5 heteroatoms each being N, O, or S, each independently comprising 0 to 5 R １ａ is substituted with a group, Each R １ａ became independent and C １－６ Alkyl, C １－６ Alkoxy, C １－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -OH, oxo, -CN, -C(O)N(R １ｂ ) (R １ｃ ), C ３－１０ cycloalkyl or heterocycloalkyl having 3 to 12 ring members and 1 to 4 heteroatoms, each of which is N, O, or S; Each R １ｂ and R １ｃ are independently hydrogen, C １－６ alkyl, or a 3- to 8-membered heterocycloalkyl having 1 to 3 heteroatoms, each independently N, O, or S; A １ , A ２ , A ３ , and A ４ Each independently represents CR ２ - or =N-, Each R ２ are independently hydrogen, C １－６ Alkyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, halogen, C １－６ Haloalkyl, C １－６ haloalkoxy, hydroxy, or -CN; L ２ is -C(O)-, -C(O)O-, -C(O)N(R ３ ) -, -S(O) ２ - or -S(O) ２ N (R ３ ) - and R ３ is hydrogen or C １－６ is alkyl, R ４ But, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, —O—C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl; wherein each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms which are each independently N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms which are each independently N, O, or S; The cycloalkyl, the heterocycloalkyl, the aryl, and the heteroaryl each independently represent 0 to 5 R ４ａ is substituted with a group, Alternatively, R ３ and R ４ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 additional heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ４ａ became independent and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -CN, -OH, oxo, -C(O)R ４ｂ , -C(O)OR ４ｂ , -OC(O)R ４ｂ , -OC(O)OR ４ｂ , -C(O)N(R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) C(O)R ４ｃ , -OC(O)N(R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) C(O)OR ４ｃ , -S(O) ２ R ４ｂ , -S(O) ２ N (R ４ｂ ) (R ４ｃ ), -N(R ４ｂ ) S (O) ２ R ４ｃ , C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, —O—C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ４ｂ and R ４ｃ is hydrogen or C １－６ is alkyl, R ５ But, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C １－６ Alkyl-OR ５ａ , -C(O)R ５ａ , -C(O)OR ５ａ , -C(O)N(R ５ａ ) (R ５ｂ ), -S(O) ２ R ５ａ , -S(O) ２ N (R ５ａ ) (R ５ｂ ), C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl; wherein each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms which are each independently N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms which are each independently N, O, or S; Each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents 0 to 4 R ５ｃ is substituted with a group, Each R ５ａ and R ５ｂ are independently hydrogen, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, hydroxy, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C １－６ Haloalkoxy, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently has 0 to 4 R ５ｄ is substituted with a group, Alternatively, R ５ａ and R ５ｂ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 additional heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｃ became independent and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -CN, oxo, -OH, -C(O)R ５ｃ１ , -C(O)OR ５ｃ１ , -OC(O)R ５ｃ１ , -OC(O)OR ５ｃ１ , -C(O)N(R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) C(O)R ５ｃ２ , -OC(O)N(R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) C(O)OR ５ｃ２ , -S(O) ２ R ５ｃ１ , -S(O) ２ N (R ５ｃ１ ) (R ５ｃ２ ), -N(R ５ｃ１ ) S (O) ２ R ５ｃ２ , C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each heterocycloalkyl and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｃ１ and R ５ｃ２ are independently hydrogen, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 10 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each heterocycloalkyl and heteroaryl independently has 0, 1, or 2 C １－６ substituted with an alkyl group, Alternatively, R ５ｃ１ and R ５ｃ２ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｄ became independent and C １－６ is alkyl or halogen; Each R ６ are independently hydrogen, C １－６ Alkyl, halogen, C １－６ haloalkyl, or oxo; 3. The compound of claim 1 or 2, wherein subscript m is 0, 1, 2, 3, 4, or 5, or a pharma- ceutically acceptable salt thereof.

4. R １ is phenyl or heteroaryl having 5-6 ring members and 1-3 heteroatoms each being N, each independently having 0-3 R １ａ is substituted with a group, Each R １ａ became independent and C １－６ Alkyl, C １－６ Alkoxy, C １－６ Hydroxyalkyl, halogen, C １－６ haloalkyl, -OH, oxo, or -CN; Each R １ｂ and R １ｃ are independently hydrogen or C １－６ The compound according to any one of claims 1 to 3, or a pharma- ceutically acceptable salt thereof, wherein R is an alkyl group.

5. R １ is phenyl, pyrrole, pyrazole, imidazole, pyridine, pyrazine, pyrimdine, or pyridazine, each independently representing 0 to 3 R １ａ is substituted with a group, Each R １ａ are independently methyl, ethyl, n-propyl, isopropyl, -OMe, -CH ２ OH, fluoro, chloro, bromo, -CHF ２ 5. The compound according to claim 1, wherein R is -R, ...

6. R １ but, Each independently is methyl, —CH ２ OH, fluoro, -CHF ２ or 0 to 2 R １ａ phenyl substituted with a group; 0 to 3 R, each independently being methyl, -OMe, F, -OH, or oxo; １ａ pyridyl substituted with a group; 1 to 2 R, each independently being methyl; １ａ pyrazole substituted with a group; 1 to 3 R, each independently being methyl or oxo; １ａ pyridazine substituted with a group, or 1 to 2 R, each of which is methyl １ａ 6. The compound according to any one of claims 1 to 5, which is a pyrazine substituted with a group, or a pharma- ceutically acceptable salt thereof.

7. R １ but, 【Chemistry 3】 7. The compound according to any one of claims 1 to 6, wherein:

8. R １ but, 【Chemistry 4】 7. The compound according to any one of claims 1 to 6, wherein:

9. R １ The compound according to any one of claims 1 to 7, wherein: 【Chemistry 5】

10. A １ , A ２ , A ３ , and A ４ Each of the above is =CR ２ 10. The compound according to any one of claims 1 to 9, wherein:

11. At least one R ２ But, C １－６ Alkyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, halogen, C １－６ Haloalkyl, C １－６ The compound of any one of claims 1 to 10, which is haloalkoxy, hydroxy, or -CN, or a pharma- ceutically acceptable salt thereof.

12. Each R ２ are independently hydrogen, C １－６ Alkyl, C １－６ Alkoxy, halogen, or C １－６ 11. The compound of any one of claims 1 to 10, or a pharma- ceutically acceptable salt thereof, which is haloalkyl.

13. Each R ２ are independently hydrogen, methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, n-propoxy, iso-propoxy, fluoro, chloro, bromo, -CH ２ F, -CHF ２ , -CF ３ , -CH ２ CH ２ F, -CH ２ CHF ２ , or -CH ２ CF ３ 13. The compound according to any one of claims 1 to 12, wherein:

14. Each R ２ are independently hydrogen, methyl, methoxy, fluoro, chloro, or CF ３ 14. The compound according to any one of claims 1 to 13, wherein:

15. Each R ２ The compound according to any one of claims 1 to 14, or a pharma- ceutically acceptable salt thereof, wherein is hydrogen or methyl.

16. A １ , A ２ , and A ４ are each ═CH—, A ３ is ═C(Me)—, ═C(OMe)—, ═C(F)—, ═C(Cl)—, or ═C(CF ３ 15. The compound according to any one of claims 1 to 14, wherein R is -R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19

17. A １ , A ２ , and A ４ are each ═CH—, A ３ The compound according to any one of claims 1 to 16, wherein is =C(Me)-, or a pharma- ceutically acceptable salt thereof.

18. 18. The compound of any one of claims 1 to 17, wherein the subscript n is 1, or a pharma- ceutically acceptable salt thereof.

19. Formula Ia 【Chemistry 6】 19. The compound of any one of claims 1 to 18, having the structure:

20. Formula Ib 【Chemistry 7】 20. The compound of any one of claims 1 to 19, having the structure:

21. Formula Ib-1 【Chemistry 8】 21. The compound according to any one of claims 1 to 20, having the structure:

22. Formula Ib-2 【Chemistry 9】 21. The compound according to any one of claims 1 to 20, having the structure:

23. L ２ But -C(O)-, -S(O) ２ - or -S(O) ２ N (R ３ ) - and R ３ But, C １－６ 23. The compound of any one of claims 1 to 22, or a pharma- ceutically acceptable salt thereof, which is alkyl.

24. L ２ But -C(O)-, -S(O) ２ - or -S(O) ２ 24. The compound according to any one of claims 1 to 23, which is N(Me)-, or a pharma- ceutically acceptable salt thereof.

25. L ２ is -C(O)- or -S(O) ２ 25. The compound according to any one of claims 1 to 24, wherein: -, or a pharma- ceutically acceptable salt thereof.

26. L ２ But -S(O) ２ 26. The compound according to any one of claims 1 to 25, wherein:

27. Formula Ic or Formula Id 【Chemistry 10】 26. The compound of any one of claims 1 to 25, having the structure:

28. Formula Ic 【Chemistry 11】 28. The compound of any one of claims 1 to 27, having the structure:

29. R ４ But, C １－６ Alkyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, wherein each heterocycloalkyl independently has 3 to 6 ring members and 1 to 3 heteroatoms, each of which is independently N, O, or S; each heteroaryl independently has 5 to 6 ring members and 1 to 4 heteroatoms, each of which is independently N, O, or S; and said cycloalkyl, said heterocycloalkyl, said aryl, and said heteroaryl each independently have 0 to 5 R ４ａ is substituted with a group, Alternatively, R ３ and R ４ taken together with the atom to which they are attached to form a heterocycloalkyl having 5 to 6 ring members and one additional heteroatom which is N, O, or S; Each R ４ａ became independent and C １－６ Alkyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ Haloalkoxy, -CN, C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 6 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 6 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently has 0, 1, or 2 C １－６ 29. The compound of any one of claims 1 to 28, or a pharma- ceutically acceptable salt thereof, which is substituted with an alkyl group.

30. R ４ But, C １－６ Alkyl, C ２－３ Alkoxyalkyl, C １－３ Hydroxyalkyl, C １－６ Haloalkyl, C ３－６ Cycloalkyl, C １－２ Alkyl-C ３－６ Cycloalkyl, heterocycloalkyl, C １－２ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－２ Alkyl-aryl, heteroaryl, or C １－２ alkyl-heteroaryl, wherein each heterocycloalkyl independently has 5-6 ring members and 1-3 heteroatoms, each independently being N or O, each heteroaryl independently has 5-6 ring members and 1-3 heteroatoms, each independently being N, O, or S, and said cycloalkyl, said heterocycloalkyl, said aryl, and said heteroaryl each independently have 0-3 R ４ａ is substituted with a group, Each R ４ａ became independent and C １－３ Alkyl, C １－３ Alkoxy, C ２－３ Alkoxyalkyl, halogen, C １－３ 30. The compound of any one of claims 1 to 29, wherein: haloalkyl, -CN, or heterocycloalkyl, where each heterocycloalkyl independently has 5 to 6 ring members and 1 to 2 heteroatoms, each independently being N or O; or a pharma- ceutically acceptable salt thereof.

31. R ４ is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, methoxymethyl, methoxyethyl, isopropoxyethyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, -CH ２ F, -CHF ２ , -CF ３ , -CH ２ CH ２ F, -CH ２ CHF ２ , -CH ２ CF ３ , C ３－６ Cycloalkyl, C １－２ Alkyl-C ３－６ Cycloalkyl, heterocycloalkyl, C １－２ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－２ Alkyl-C ６－１２ aryl or heteroaryl; wherein each cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; each heterocycloalkyl is oxetane, tetrahydrofuran, pyrrolidine, tetrahydropyran, piperidine, or morpholine; each aryl is phenyl; each heteroaryl is pyrrole, pyridine, pyrazole, imidazole, pyridazine, pyrimidine, pyrazine, isoxazole, oxazole, isothiazole, thiazole, or triazole; The cycloalkyl, the heterocycloalkyl, the aryl, and the heteroaryl each independently represent 0 to 3 R ４ａ is substituted with a group, Each R ４ａ are independently methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, isopropoxy, methoxymethyl, methoxyethyl, ethoxymethyl, fluoro, chloro, bromo, -CH ２ F, -CHF ２ , -CF ３ , -CH ２ CH ２ F, -CH ２ CHF ２ , -CH ２ CF ３ 31. The compound according to any one of claims 1 to 30, wherein the aryl group is -CN, -CN, tetrahydrofuran, pyrrolidine, tetrahydropyran, piperidine, or morpholine, or a pharma- ceutically acceptable salt thereof.

32. R ４ is methyl, n-propyl, iso-butyl, -CH(OH)CH ３ , methoxyethyl, isopropoxyethyl, CH ２ CF ３ , C ３－６ Cycloalkyl, C １－２ Alkyl-C ３－６ Cycloalkyl, heterocycloalkyl, C １－２ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－２ Alkyl-C ６－１２ aryl or heteroaryl; where each cycloalkyl is cyclopropyl or cyclobutyl; each heterocycloalkyl is oxetane, tetrahydrofuran, or morpholine; each aryl is phenyl; each heteroaryl is pyridine, pyrazole, pyridazine, isoxazole, thiazole, or triazole, and said heteroaryl is selected from 0 to 2 R ４ａ is substituted with a group, Each R ４ａ are independently methyl, ethyl, n-propyl, iso-propyl, methoxy, methoxyethyl, fluoro, -CHF ２ , -CF ３ , -CH ２ CHF ２ , -CH ２ CF ３ 32. The compound of any one of claims 1 to 31, or a pharma- ceutically acceptable salt thereof, which is -CN, or tetrahydropyran.

33. R ４ Each of these has 0 to 2 R ４ａ a pyridine, pyrazole, thiazole, or triazole substituted with a group; Each R ４ａ are independently methyl, ethyl, n-propyl, iso-propyl, methoxy, methoxyethyl, fluoro, -CHF ２ , -CF ３ , -CH ２ CHF ２ , -CH ２ CF ３ 32. The compound of any one of claims 1 to 31, or a pharma- ceutically acceptable salt thereof, which is -CN, or tetrahydropyran.

34. R ４ is methyl, n-propyl, iso-butyl, -CH(OH)CH ３ , methoxyethyl, isopropoxyethyl, CH ２ CF ３ , 【Chemistry 12-1】 【Chemistry 12-2】 33. The compound according to any one of claims 1 to 32, wherein:

35. L ２ is —C(O)—, R ４ Methyl, -CH(OH)CH ３ or 【Chemistry 13】 33. The compound according to any one of claims 1 to 32, wherein:

36. L ２ But -S(O) ２ - and R ４ Methyl, n-propyl, iso-butyl, -methoxyethyl, isopropoxyethyl, CH ２ CF ３ , 【Chemistry 14-1】 【Chemistry 14-2】 33. The compound according to any one of claims 1 to 32, wherein:

37. L ２ is -S(O)N(Me)-, R ４ Methyl or 【Chemistry 15】 33. The compound according to any one of claims 1 to 32, wherein:

38. R ５ But, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ２－６ Alkoxyalkyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, —C(O)R ５ａ , C １－６ Alkyl-C(O)R ５ａ , -S(O) ２ R ５ａ , C ３－８ Cycloalkyl, C １－６ Alkyl-C ３－８ Cycloalkyl, heterocycloalkyl, C １－６ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－６ Alkyl-C ６－１２ Aryl, heteroaryl, or C １－６ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 6 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; each heteroaryl independently has 5 to 6 ring members and 1 to 4 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently have 0 to 4 R ５ｃ is substituted with a group, Each R ５ａ and R ５ｂ are independently hydrogen or C １－６ is alkyl, Alternatively, R ５ａ and R ５ｂ are combined with the atom to which they are attached to form a heterocycloalkyl having 3 to 12 ring members and 1 to 3 additional heteroatoms, each independently being N, O, or S, where said heterocycloalkyl has 0, 1, or 2 C １－６ substituted with an alkyl group, Each R ５ｃ became independent and C １－６ Alkyl, C １－６ Alkoxy, C ２－６ Alkoxyalkyl, hydroxy, C １－６ Hydroxyalkyl, halogen, C １－６ Haloalkyl, C １－６ 38. The compound of any one of claims 1 to 37, which is haloalkoxy, -CN, oxo, or -OH, or a pharma- ceutically acceptable salt thereof.

39. R ５ But, C １－６ Alkyl, C ２－６ Alkenyl, C １－６ Hydroxyalkyl, C １－６ Haloalkyl, —C(O)R ５ａ , C １－２ Alkyl-C(O)R ５ａ , C ３－６ Cycloalkyl, C １－２ Alkyl-C ３－６ Cycloalkyl, heterocycloalkyl, C １－２ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－２ Alkyl-C ６－１２ Aryl, or C １－２ alkyl-heteroaryl, where each heterocycloalkyl independently has 3 to 6 ring members and 1 to 2 heteroatoms, each independently being N or O; each heteroaryl independently has 5 to 6 ring members and 1 to 3 heteroatoms, each independently being N, O, or S; and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently have 0 to 2 R ５ｃ is substituted with a group, Each R ５ａ became independent and C １－６ is alkyl, Each R ５ｃ became independent and C １－３ Alkyl, C １－３ Alkoxy, halogen, C １－３ 39. The compound of any one of claims 1 to 38, or a pharma- ceutically acceptable salt thereof, which is haloalkyl, -CN, oxo, or -OH.

40. R ５ But, C １－６ Alkyl, C １－６ Haloalkyl, or C １－２ Alkyl-C ３－６ cycloalkyl, where each cycloalkyl independently represents 0 to 2 R ５ｃ is substituted with a group, Each R ５ｃ became independent and C １－３ Alkyl, C １－３ Alkoxy, halogen, C １－３ 39. The compound of any one of claims 1 to 38, or a pharma- ceutically acceptable salt thereof, which is haloalkyl, -CN, oxo, or -OH.

41. R ５ is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, C ４－６ Alkenyl, C ４－６ Hydroxyalkyl, -CH ２ F, -CHF ２ , -CF ３ , -CH ２ CH ２ F, -CH ２ CHF ２ , -CH ２ CF ３ , -CH ２ CHFCH ３ , -CH ２ CF ２ CH ３ , -CH ２ CH ２ CF ３ , -CH ２ CF (CH ３ ) ２ , -CH ２ CH ２ CH ２ CF ３ , -CH ２ CH (CH ３ ) (CF ３ ), -CH ２ C (CH ３ ) ２ (CF ３ ), -C(O)R ５ａ , C １－２ Alkyl-C(O)R ５ａ , C ３－６ Cycloalkyl, C １－２ Alkyl-C ３－６ Cycloalkyl, heterocycloalkyl, C １－２ Alkyl-heterocycloalkyl, C ６－１２ Aryl, C １－２ Alkyl-C ６－１２ Aryl, or C １－２ alkyl-heteroaryl; wherein each cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; each heterocycloalkyl is oxetane, tetrahydrofuran, or tetrahydropyran; each aryl is phenyl; each heteroaryl is pyrrole, pyridine, pyrazole, imidazole, pyridazine, pyrimidine, pyrazine, isoxazole, oxazole, isothiazole, thiazole, or triazole; Each cycloalkyl, aryl, and heteroaryl independently represents 0 to 2 R ５ｃ is substituted with a group, Each R ５ａ is independently methyl, ethyl, n-propyl, or iso-propyl; Each R ５ｃ are independently methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, n-propoxy, iso-propoxy, fluoro, chloro, bromo, -CH ２ F, -CHF ２ , -CF ３ , -CH ２ CF ３ 40. The compound of any one of claims 1 to 39, wherein R is -CN, oxo, or -OH, or a pharma- ceutically acceptable salt thereof.

42. R ５ Ethyl, isopropyl, isobutyl, 【Chemistry 16-1】 【Chemistry 16-2】 42. The compound according to any one of claims 1 to 41, wherein:

43. R ６ is hydrogen, C １－６ alkyl, or oxo; 43. The compound of any one of claims 1 to 42, wherein subscript m is 0, 1, or 2, or a pharma- ceutically acceptable salt thereof.

44. R ６ is hydrogen, methyl, or oxo; 44. The compound of any one of claims 1 to 43, wherein subscript m is 0, 1, or 2, or a pharma- ceutically acceptable salt thereof.

45. 45. The compound of any one of claims 1 to 44, wherein subscript m is 0; or a pharma- ceutically acceptable salt thereof.

46. R １ but, 【Chemistry 17】 and A １ , A ２ , and A ４ are each ═CH—, A ３ is ═C(Me)—, L ２ But -S(O) ２ - and R ４ Each of these has 0 to 2 R ４ａ a pyridine, pyrazole, thiazole, or triazole substituted with a group; Each R ４ａ are independently methyl, ethyl, n-propyl, iso-propyl, methoxy, methoxyethyl, fluoro, -CHF ２ , -CF ３ , -CH ２ CHF ２ , -CH ２ CF ３ , —CN, or tetrahydropyran; R ５ But, C １－６ Alkyl, C １－６ Haloalkyl, or C １－２ Alkyl-C ３－６ cycloalkyl, where each cycloalkyl independently represents 0 to 2 R ５ｃ is substituted with a group, Each R ５ｃ became independent and C １－３ Alkyl, C １－３ Alkoxy, halogen, C １－３ haloalkyl, -CN, oxo, or -OH; The subscript m is 0; 45. The compound of any one of claims 1 to 44, wherein the subscript n is 1, or a pharma- ceutically acceptable salt thereof.

47. R １ but, 【Chemistry 18】 and A １ , A ２ , and A ４ are each ═CH—, A ３ is ═C(Me)—, L ２ But -S(O) ２ - and R ４ Each of them has one R ４ａ a pyrazole or triazole substituted with a group, R ４ａ is methyl, ethyl, n-propyl, or iso-propyl; R ５ But, C １－６ is haloalkyl, The subscript m is 0; 45. The compound of any one of claims 1 to 44, wherein the subscript n is 1, or a pharma- ceutically acceptable salt thereof.

48. R １ but, 【Chemistry 19】 and A １ , A ２ , and A ４ are each ═CH—, A ３ is ═C(Me)—, ═C(OMe)—, ═C(F)—, ═C(Cl)—, or ═C(CF ３ ) - and L ２ But -C(O)-, -S(O) ２ - or -S(O) ２ N(Me)-, R ４ is methyl, n-propyl, iso-butyl, -CH(OH)CH ３ , methoxyethyl, isopropoxyethyl, CH ２ CF ３ , 【Chemistry 20-1】 【Chemistry 20-2】 and R ５ Ethyl, isopropyl, isobutyl, 【Chemistry 21-1】 【Chemistry 21-2】 and R ６ is hydrogen, methyl, or oxo; 45. The compound of any one of claims 1 to 44, wherein subscript m is 0, 1, or 2, or a pharma- ceutically acceptable salt thereof.

49. 49. The compound of any one of claims 1 to 48, which is a compound of Table 1A, Table 1B, Table 1C, Table 1D, Table 1E, Table 1F, Table 1G, Table 1H, Table 1I, Table 1J, or Table 1K, or a pharma- ceutically acceptable salt thereof. 【Request 50】 【Chemical 22-1】 【Chemistry 22-2】 【Chemistry 22-3】 【Chemistry 22-4】 50. The compound according to any one of claims 1 to 49, which is a compound having the structure: or a pharma- ceutically acceptable salt thereof.

51. 【Chemical 23】 51. The compound according to any one of claims 1 to 50, which has the structure:

52. 【Catalogue 24】 51. The compound according to any one of claims 1 to 50, which has the structure:

53. 【Chemical 25】 51. The compound according to any one of claims 1 to 50, which has the structure:

54. 【Catalogue 26】 51. The compound according to any one of claims 1 to 50, which has the structure:

55. 【Catalogue 27】 51. The compound according to any one of claims 1 to 50, which has the structure:

56. 【Catalogue 28】 51. The compound according to any one of claims 1 to 50, which has the structure:

57. 【Catalogue 29】 51. The compound according to any one of claims 1 to 50, which has the structure:

58. 【Chemical 30】 51. The compound according to any one of claims 1 to 50, which has the structure:

59. 【Chemical 31】 51. The compound according to any one of claims 1 to 50, which has the structure:

60. 【Catalog 32】 51. The compound according to any one of claims 1 to 50, which has the structure:

61. 【Chemical 33】 51. The compound according to any one of claims 1 to 50, which has the structure:

62. 62. A pharmaceutical composition comprising a compound according to any one of claims 1 to 61 or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable excipient.

63. 63. A method for treating a disorder or condition by modulating the glucocorticoid receptor, comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound according to any one of claims 1 to 61 or a pharma- ceutically acceptable salt thereof, or a pharmaceutical composition according to claim 62, thereby treating said disorder or condition.

64. 63. A method for treating a disorder or condition by antagonizing the glucocorticoid receptor, comprising administering to a subject in need of such treatment an effective amount of a compound according to any one of claims 1 to 61 or a pharma- ceutically acceptable salt thereof, or a pharmaceutical composition according to claim 62.

65. 65. The method of claim 63 or 64, wherein the disorder or condition is selected from the group consisting of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), antipsychotic-induced weight gain, cancer, Cushing's disease, Cushing's syndrome, psychotic major depression, nonalcoholic steatohepatitis, and obesity.

66. A compound according to any one of claims 1 to 61 or a pharma- ceutically acceptable salt thereof, or a pharmaceutical composition according to claim 62, for use in a method for treating a disorder or condition by modulating the glucocorticoid receptor.

67. 63. A compound according to any one of claims 1 to 61 or a pharma- ceutically acceptable salt thereof, or a pharmaceutical composition according to claim 62, for use in a method for treating a disorder or condition by antagonizing the glucocorticoid receptor.

68. 63. Use of a compound according to any one of claims 1 to 61 or a pharma- ceutically acceptable salt thereof, or a pharmaceutical composition according to claim 62, in the manufacture of a medicament for treating a disorder or condition by modulating the glucocorticoid receptor.

69. 63. Use of a compound according to any one of claims 1 to 61 or a pharma- ceutically acceptable salt thereof, or a pharmaceutical composition according to claim 62, in the manufacture of a medicament for treating a disorder or condition by antagonizing the glucocorticoid receptor.

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