Heterocycle derivatives for treating trpm3 mediated disorders

A method of treating pain comprising administering to a subject in need of such treatment a compound of formula (I), a stereo-isomeric form, a physiologically acceptable salt, solvate and/or polymorph thereof

• wherein
• R1 represents —F, —Cl, —Br, —I, —CN, —RW, —ORW, —OC(═O)RW, —NRWRX, —NRWC(═O)RX, —SRW, —S(═O)RW, —S(═O)2RW, —C(═O)RW, —C(═O)ORW, or —C(═O)NRWRX;
• Q represents —NR3R4;
• R3 represents —OH or —R;
• R4 represents —R or —S(═O)2RY;
• or R3 and R4 together form a 4, 5, 6, 7 or 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, O and S, saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• T represents —O— and U represents —CR5R5′—;
• or T represents —CR5R5′— and U represents —O—;
• R5 and R5′ independently of one another represent —RY;
• R6, R7 and R8 independently of one another represent —F, —Cl, —Br, —I, —CN, —NO2, —SF5, —RW, —ORW, —OC(═O)RW, —NRWRX, —NRWC(═O)RX, —SRW, —S(═O)RW, —S(═O)2RW, —C(═O)RW, —C(═O)ORW, or —C(═O)NRWRX;
• V represents 3-14-membered heterocycloalkyl, saturated or unsaturated;
• or 5-14-membered heteroaryl;
• in each case unsubstituted, mono- or polysubstituted with substituents independently of one another selected from —F, —Cl, —Br, —I, —CN, —NO, —NO2, ═O, ═S, —SF5, —RY, —ORY, —OC(═O)R, —NRYRZ, —NRYC(═O)RZ, —SRY, —S(═O)RY, —S(═O)2RY, —C(═O)RY, —C(═O)ORY, or —C(═O)NRYRZ;
• wherein
• RW and RX independently of one another in each case independently represent
• —H;
• C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;
• 3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• wherein said 3-14-membered cycloalkyl is optionally connected through —C1-C6-alkylene- or —C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• or
• 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• wherein said 3-14-membered heterocycloalkyl is optionally connected through —C1-C6-alkylene- or —C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• RY and RZ independently of one another in each case independently represent
• —H;
• C1-C6-alkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• C1-C6-heteroalkyl, saturated or unsaturated, unsubstituted, mono- or poly substituted;
• 3-14-membered cycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• wherein said 3-14-membered cycloalkyl is optionally connected through —C1-C6-alkylene- or —C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• 3-14-membered heterocycloalkyl, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• wherein said 3-14-membered heterocycloalkyl is optionally connected through —C1-C6-alkylene- or —C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• 6-14-membered aryl, unsubstituted, mono- or polysubstituted;
• wherein said 6-14-membered aryl is optionally connected through —C1-C6-alkylene- or —C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• or
• 5-14-membered heteroaryl, unsubstituted, mono- or polysubstituted;
• wherein said 5-14-membered heteroaryl is optionally connected through —C1-C6-alkylene- or —C1-C6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted;
• or RY and RZ together form a 4, 5, 6, 7 or 8 membered heterocycle containing 1 to 3 heteroatoms selected from N, O and S, saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• and wherein “mono- or polysubstituted” in each case independently means substituted with one or more substituents independently of one another selected from —F, —Cl, —Br, —I, —CN, —C1-6-alkyl, —CF3, —CF2H, —CFH2, —CF2Cl, —CFCl2, —C1-6-alkylene-CF3, —C1-6-alkylene-CF2H, —C1-6-alkylene-CFH2, —C1-6-alkylene-O—CF3, —C1-6-alkylene-O—CF2H, —C1-6-alkylene-O—CFH2, —C1-6-alkylene-NH—C1-6-alkylene-CF3, —C1-6-alkylene-N(C1-6-alkyl)-C1-6-alkylene-CF3, —C(═O)—C1-6-alkyl, —C1-6-alkylene-C(═O)—C1-6-alkyl, —C(═O)OH, —C1-6-alkylene-C(═O)—OH, —C(═O)—OC1-6-alkyl, —C1-6-alkylene-C(═O)—OC1-6-alkyl, —C(═O)O—C1-6-alkylene-CF3, —C(═O)—NH2, —C1-6-alkylene-C(═O)—NH2, —C(═O)—NH(C1-6-alkyl), —C1-6-alkylene-C(═O)—NH(C1-6-alkyl), —C(═O)—N(C1-6-alkyl)2, —C1-6-alkylene-C(═O)—N(C1-6-alkyl)2, —C(═O)—NH(OH), —C1-6-alkylene-C(═O)—NH(OH), —OH, —C1-6-alkylene-OH, ═O, —OCF3, —OCF2H, —OCFH2, —OCF2Cl, —OCFCl2, —O—C1-6-alkyl, —C1-6-alkylene-O—C1-6-alkyl, —O—C1-6-alkylene-O—C1-6-alkyl, —O—C1-6-allylene-NH2, —O—C1-6-alkylene-NH—C1-6-alkyl, —O—C1-6-alkylene-N(C1-6-alkyl)2, —O—C(═O)—C1-6-alkyl, —C1-6-alkylene-O—C(═O)—C1-6-alkyl, —O—C(═O)—O—C1-6-alkyl, —C1-6-alkylene-O—C(═O)—O—C1-6-alkyl, —O—C(═O)—NH(C1-6-alkyl), —C1-6-alkylene-O—C(═O)—NH(C1-6-alkyl), —O—C(═O)—N(C1-6-alkyl)2, —C1-6-alkylene-O—C(═O)—N(C1-6-alkyl)2, —O—S(═O)2—NH2, —C1-6-alkylene-O—S(═O)2—NH2, —O—S(═O)2—NH(C1-6-alkyl), —C1-6-alkylene-O—S(═O)2—NH(C1-6-alkyl), —O—S(═O)2—N(C1-6-alkyl)2, —C1-6-alkylene-O—S(═O)2—N(C1-6-alkyl)2, —NH2, —NO, —NO2, —C1-6-alkylene-NH2, —NH(C1-6-alkyl), —N(3-14-membered cycloalkyl)(C1-6-alkyl), —N(C1-6-alkyl)-C1-6-alkylene-OH, —N(H)—C1-6-alkylene-OH, —C1-6-alkylene-NH(C1-6-alkyl), —N(C1-6-alkyl)2, —C1-6-alkylene-N(C1-6-alkyl)2, —NH—C(═O)—C1-6-alkyl, —C1-6-alkylene-NH—C(═O)—C1-6-alkyl, —NH—C(═O)—O—C1-6-alkyl, —C1-6-alkylene-NH—C(═O)—O—C1-6-alkyl, —NH—C(═O)—NH2, —C1-6-alkylene-NH—C(═O)—NH2, —NH—C(═O)—NH(C1-6-alkyl), —C1-6-alkylene-NH—C(═O)—NH(C1-6-alkyl), —NH—C(═O)—N(C1-6-alkyl)2, —C1-6-alkylene-NH—C(═O)—N(C1-6-alkyl)2, —N(C1-6-alkyl)-C(═O)—C1-6-alkyl, —C1-6-alkylene-N(C1-6-alkyl)-C(═O)—C1-6-alkyl, —N(C1-6-alkyl)-C(═O)—O—C1-6-alkyl, —C1-6-alkylene-N(C1-6-alkyl)-C(═O)—O—C1-6-alkyl, —N(C1-6-alkyl)-C(═O)—NH2, —C1-6-alkylene-N(C1-6-alkyl)-C(═O)—NH2, —N(C1-6-alkyl)-C(═O)—NH(C1-6-alkyl), —C1-6-alkylene-N(C1-6-alkyl)-C(═O)—NH(C1-6-alkyl), —N(C1-6-alkyl)-C(═O)—N(C1-6-alkyl)2, —C1-6-alkylene-N(C1-6-alkyl)-C(═O)—N(C1-6-alkyl)2, —NH—S(═O)20H, —C1-6-alkylene-NH—S(═O)2OH, —NH—S(═O)2—C1-6-alkyl, —C1-6-alkylene-NH—S(═O)2—C1-6-alkyl, —NH—S(═O)2—O—C1-6-alkyl, —C1-6-alkylene-NH—S(═O)2—O—C1-6-alkyl, —NH—S(═O)2—NH2, —C1-6-alkylene-NH—S(═O)2—NH2, —NH—S(═O)2—NH(C1-6-alkyl), —C1-6-alkylene-NH—S(═O)2—NH(C1-6-alkyl), —NH—S(═O)2N(C1-6-alkyl)2, —C1-6-alkylene-NH—S(═O)2N(C1-6-alkyl)2, —N(C1-6-alkyl)-S(═O)2—OH, —C1-6-alkylene-N(C1-6-alkyl)-S(═O)2—OH, —N(C1-6-alkyl)-S(═O)2—C1-6-alkyl, —C1-6-alkylene-N(C1-6-alkyl)-S(═O)2—C1-6-alkyl, —N(C1-6-alkyl)-S(═O)2—O—C1-6-alkyl, —C1-6-alkylene-N(C1-6-alkyl)-S(═O)2—O—C1-6-alkyl, —N(C1-6-alkyl)-S(═O)2—NH2, —C1-6-alkylene-N(C1-6-alkyl)-S(═O)2—NH2, —N(C1-6-alkyl)-S(═O)2—NH(C1-6-alkyl), —C1-6-alkylene-N(C1-6-alkyl)-S(═O)2—NH(C1-6-alkyl), —N(C1-6-alkyl)-S(═O)2—N(C1-6-alkyl)2, —C1-6-alkylene-N(C1-6-alkyl)-S(═O)2—N(C1-6-alkyl)2, —SH, ═S, —SF5, —SCF3, —SCF2H, —SCFH2, —S—C1-6-alkyl, —C1-6-alkylene-S—C1-6-alkyl, —S(═O)—C1-6-alkyl, —C1-6-alkylene-S(═O)—C1-6-alkyl, —S(═O)2—C1-6-alkyl, —C1-6-alkylene-S(═O)2—C1-6-alkyl, —S(═O)2—OH, —C1-6-alkylene-S(═O)2—OH, —S(═O)2—O—C1-6-alkyl, —C1-6-alkylene-S(═O)2—O—C1-6-alkyl, —S(═O)2—NH2, —C1-6-alkylene-S(═O)2—NH2, —S(═O)2—NH(C1-6-alkyl), —C1-6-alkylene-S(═O)2—NH(C1-6-alkyl), —S(═O)2—N(C1-6-alkyl)2, —C1-6-alkylene-S(═O)2—N(C1-6-alkyl)2, 3-14-membered cycloalkyl, —C1-6-alkylene-(3-14-membered cycloalkyl), 3 to 14-membered heterocycloalkyl, —C1-6-alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, —C1-6-alkylene-phenyl, 5 to 14-membered heteroaryl, —C1-6-alkylene-(5 to 14-membered heteroaryl), —O-(3-14-membered cycloalkyl), —O-(3 to 14-membered heterocycloalkyl), —O-phenyl, —O-(5 to 14-membered heteroaryl), —C(═O)-(3-14-membered cycloalkyl), —C(═O)-(3 to 14-membered hetero-cycloalkyl), —C(═O)-phenyl, —C(═O)-(5 to 14-membered heteroaryl), —S(═O)2-(3-14-membered cycloalkyl), —S(═O)2-(3 to 14-membered heterocycloalkyl), —S(═O)2-phenyl, —S(═O)2-(5 to 14-membered heteroaryl);
• with the proviso that the following compounds and their salts are excluded