Substituted Benzo[d]isoxazol-3-yl Amine Compounds as Analgesics

A substituted benzo[d]isoxazol-3-yl amine compound corresponding to formula I

• wherein
• R1, R2, R3 and R4 each independently denote H, F, Cl, Br, I, —CN, —NO2, —SF5, —NR7R8, —OR9, —SR10, —C(═O)OR11, —(C═O)NR12R13, —S(═O)2R14, —C(═O)R15, —NR16—S(═O)2R17, C1-10-alkyl, C2-10-alkenyl, or C2-10-alkinyl;
• R5 denotes —C(═S)NR21R22 or (CHR6)n—R25, wherein
• n=1, 2 or 3;
• R6 denotes H, C3-8-cycloalkyl or C1-6-alkyl, and
• R25 denotes aryl or heteroaryl;
• R7 and R8 each independently denote H, —C(═O)R14 or C1-10-alkyl, or
• R7 and R8 together with the nitrogen atom to which they are bound form a morpholine, piperidine or pyrrolidine ring;
• R9, R10, R11 and R16 each independently denote H, C1-10-alkyl, C2-10-alkenyl, C2-10 alkinyl, C3-8-cycloalkyl, —(C1-5-alkylene)-C3-8-cycloalkyl, heterocycloalkyl, —(C1-5-alkylene)-heterocycloalkyl, aryl, heteroaryl, —(C1-5-alkylene)-aryl, or —(C1-5-alkylene)-heteroaryl;
• R12 and R13 each independently denote H or C1-10-alkyl, or
• R12 and R13 together with the nitrogen atom to which they are bound form a morpholine, piperidine or pyrrolidine ring;
• R14 denotes —NR7R8, C1-10-alkyl, C2-10-alkenyl, C2-10-alkinyl, C3-8-cycloalkyl, —(C1-5-alkylene)-C3-8-cycloalkyl, heterocycloalkyl, —(C1-5-alkylene)-heterocycloalkyl, aryl, heteroaryl, —(C1-5-alkylene)-aryl or —(C1-5-alkylene)-heteroaryl;
• R15 and R17 each independently denote C1-10-alkyl, C2-10-alkenyl, C2-10-alkinyl, C3-8-cycloalkyl, —(C1-5-alkylene)-C3-8-cycloalkyl, heterocycloalkyl, —(C1-5-alkylene)-heterocycloalkyl, aryl, heteroaryl, —(C1-5-alkylene)-aryl or —(C1-5-alkylene)-heteroaryl;
• R21 and R22 each independently denote H, C1-10-alkyl, C2-10-alkenyl, C2-10-alkinyl, C3-8-cycloalkyl, —(C1-5-alkylene)-C3-8-cycloalkyl, heterocycloalkyl, —(C1-5-alkylene)-heterocycloalkyl, aryl, heteroaryl, —(C1-5-alkylene)-aryl or —(C1-5-alkylene)-heteroaryl;
• wherein
• the aforementioned C1-10-alkyl, C2-10-alkenyl and C2-10-alkinyl groups may each be linear or branched and may optionally be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, COOH, COOC1-4-alkyl, —CN, —OH, —SH, —O—C1-2-alkyl, —S—C1-2-alkyl and —NH2;
• the aforementioned C3-8-cycloalkyl groups may each optionally be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, —CN, —OH, —SH, —C1-5-alkyl, —O—C1-2-alkyl, —S—C1-2-alkyl and —NH2;
• the aforementioned heterocycloalkyl groups each comprise a 4-, 5-, 6- or 7-membered ring containing 1 or 2 heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen, and may optionally be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, —CN, —OH, —SH, —C1-5-alkyl, —O—C1-2-alkyl, —S—C1-2-alkyl and —NH2;
• the aforementioned aryl groups each independently denote a phenyl, anthracenyl or naphthyl group, which optionally may be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —CF3, —OCF3, —SCF3, C(═O)C1-5-alkyl,
• —NO2, cyclohexyl, —SF5, —CN, —OH, —SH, —C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —O(C═O)C1-2-alkyl, —C(═O)—OC1-5-alkyl, —NH2, —N(H)(C1-5-alkyl), —N(C1-5-alkyl)(C1-5-alkyl), —C(═O)NH2, —C(═O)N(H)(C1-5-alkyl), —C(═O)N(C1-5-alkyl)(C1-5-alkyl), —S(═O)2NH2, —S(═O)2N(H)(C1-5-alkyl), —S(═O)2N(C1-5-alkyl)(C1-5-alkyl), —S(═O)2-phenyl, —S(═O)2—C1-5-alkyl, phenyl, phenoxy, benzyl, benzyloxy, thiophenyl (thienyl), furanyl and pyridinyl;
• and
• the aforementioned heteroaryl groups each independently comprise a 5- or 6-membered ring containing 1, 2 or 3 heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen, and may optionally be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, —CF3, —OCF3, —SCF3, —SF5, —CN, —OH, —SH, —C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —C(═O)—OC1-5-alkyl, —NH2, —N(H)(C1-5-alkyl), —N(C1-5-alkyl)(C1-5-alkyl), —C(═O)NH2, —C(═O)N(H)(C1-5-alkyl), —C(═O)N(C1-5-alkyl)(C1-5-alkyl), —S(═O)2NH2, —S(═O)2N(H)(C1-5-alkyl), —S(═O)2N(C1-5-alkyl)(C1-5-alkyl), —S(═O)2-phenyl, —S(═O)2—C1-5-alkyl, phenyl, phenoxy, benzyl, thiophenyl (thienyl), furanyl and pyridinyl;
• or a pharmaceutically acceptable salt or solvate thereof.