Novel Vanilloid Receptor Ligands and Use Thereof for the Production of Pharmaceutical Preparations

Substituted compounds of the general formula A,

• in which
• X denotes O, S or N—CN;
• Y denotes —NH2;
• —NHR30;
• —NR31R32 or denote a linear or branched, saturated or unsaturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• n denotes 0, 1, 2, 3 or 4;
• R1, R2, R3 and R4, mutually independently, in each case denote H;
• F;
• Cl;
• Br;
• I;
• —SF5;
• —NO2;
• —CF3;
• —CN;
• —NH2;
• —OH;
• —SH;
• —C(═O)—NH2;
• —S(═O)2—NH2;
• —C(═O)—NH—OH;
• —C(═O)—OH;
• —C(═O)—H;
• —S(═O)2—OH;
• —NHR11;
• —NR12R13;
• —OR14;
• —SR15;
• —C(═O)—NHR16;
• —C(═O)—NR17R18;
• —S(═O)2—NHR19;
• —S(═O)2—NR2OR21;
• —C(═O)—OR22;
• —C(═O)—R23;
• —S(═O)—R24;
• —S(═O)2—R24 or denote a linear or branched, saturated or unsaturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• R5 denotes H;
• F;
• Cl;
• Br;
• I;
• —SF5;
• —NO2;
• —CF3;
• —CF2Cl;
• —CN;
• —NH2;
• —OH;
• —SH;
• —C(═O)—NH2;
• —S(═O)2—NH2;
• —C(═O)—NH—OH;
• —C(═O)—OH;
• —C(═O)—H;
• —S(═O)2—OH;
• —NHR11;
• —NR12R13;
• —OR14;
• —SR15;
• —C(═O)—NHR16;
• —C(═O)—NR17R18;
• —S(═O)2—NHR19;
• —S(═O)2—NR2OR21;
• —C(═O)—OR22;
• —C(═O)—R23, —S(═O)2—R24;
• —S(═O)—R24;
• denotes a linear or branched, unsaturated or saturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• or denotes an unsaturated or saturated, unsubstituted or at least monosubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-membered cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, which residue is in each case attached to the parent structure via a carbon atom in the ring of the cycloaliphatic residue;
• T denotes C—R6 and U denotes C—R7 and V denotes N and W denotes C—R8 or
• T denotes C—R6 and U denotes N and V denotes C—R9 and W denotes C—R8 or
• T denotes N and U denotes C—R7 and V denotes C—R9 and W denotes C—R8 or
• T denotes N and U denotes N and V denotes C—R9 and W denotes C—R8 or
• T denotes N and U denotes C—R7 and V denotes N and W denotes C—R8 or
• T denotes C—R6 and U denotes N and V denotes N and W denotes C—R8 or
• T denotes C—R6 and U denotes C—R7 and V denotes C—R9 and W denotes C—R10;
• R6 and R7, mutually independently, in each case denote H;
• F;
• Cl;
• Br;
• I;
• —SFS;
• —NO2;
• —CF3;
• —CF2C1;
• —CN;
• —NH2;
• —OH;
• —SH;
• —C(═O)—NH2;
• —S(═O)2—NH2;
• —C(═O)—NH—OH;
• —C(═O)—OH;
• —C(═O)—H;
• —S(═O)2—OH;
• —NHR11;
• —NR12R13;
• —OR14;
• —SR15;
• —C(═O)—NHR16;
• —C(═O)—NR17R18;
• —S(═O)2—NHR19;
• —S(═O)2—NR20R21;
• —C(═O)—OR22;
• —C(═O)—R23, —S(═O)—R24;
• —S(═O)2—R24;
• or denote a linear or branched, saturated or unsaturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• or denote an unsubstituted or at least monosubstituted 6- or 10-membered aryl residue, which may be attached via a linear or branched, substituted or at least monosubstituted C1-6 alkylene group or C2-6 alkenylene group or C2-6 alkynylene group;
• R8 denotes H;
• F;
• Cl;
• Br;
• I;
• —SF5;
• —NO2;
• —CF3;
• —CF2Cl;
• —CN;
• —NH2;
• —OH;
• —SH;
• —C(═O)—NH2;
• —S(═O)2—NH2;
• —C(═O)—NH—OH;
• —C(═O)—OH;
• —C(═O)—H;
• —S(═O)2—OH;
• —NHR11;
• —NR12R13;
• —OR14;
• —SR15;
• —C(═O)—NHR16;
• —C(═O)—NR17R18;
• —S(═O)2—NHR19;
• —S(═O)2—NR20R21;
• —C(═O)—OR22;
• —C(═O)—R23;
• —S(═O)—R24;
• —S(═O)2—R24;
• —C(═NH)—NH2;
• —C(═NH)—NH—R27;
• —N═C(NH2)2;
• —N═C(NHR28)(NHR29);
• denotes a linear or branched, saturated or unsaturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• denotes an unsaturated or saturated, unsubstituted or at least monosubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-membered cycloaliphatic residue optionally comprising at least one heteroatom as a ring member, which residue is in each case attached to the parent structure via a carbon atom in the ring of the cycloaliphatic residue and may be fused with a saturated or unsaturated, unsubstituted or at least monosubstituted mono- or polycyclic ring system and/or be attached via a linear or branched, unsubstituted or at least monosubstituted C1-6 alkylene group or C2-6 alkenylene group or C2-6 alkynylene group;
• or denotes an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, which may be fused with a saturated or unsaturated, unsubstituted or at least monosubstituted mono- or polycyclic ring system and/or be attached via a linear or branched, unsubstituted or at least monosubstituted C1-6 alkylene group or C2-6 alkenylene group or C2-6 alkynylene group;
• R9 denotes H;
• F;
• Cl;
• Br;
• I;
• —SF5;
• —NO2;
• —CF3;
• —CF2Cl;
• —CN;
• —NH2;
• —OH;
• —SH;
• —C(═O)—NH2;
• —S(═O)2—NH2;
• —C(═O)—NH—OH;
• —C(═O)—OH;
• —C(═O)—H;
• —S(═O)2—OH;
• —NHR11;
• —NR12R13;
• —OR14;
• —SR15;
• —C(═O)—NHR16;
• —C(═O)—NR17R18;
• —S(═O)2—NHR19;
• —S(═O)2—NR2OR21;
• —C(═O)—OR22;
• —C(═O)—R23;
• —S(═O)—R24;
• —S(═O)2—R24 or denotes a linear or branched, saturated or unsaturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• R10 denotes —SF5;
• —NO2;
• —CF3;
• —CF2C1;
• —CN;
• —NH2;
• —OH;
• —SH;
• —C(═O)—NH2;
• —S(═O)2—NH2;
• —C(═O)—NH—OH;
• —C(═O)—OH;
• —C(═O)—H;
• —S(═O)2—OH;
• —NHR11;
• —NR12R13;
• —OR14;
• —SR15;
• —C(═O)—NHR16;
• —C(═O)—NR17R18;
• —S(═O)2—NHR19;
• —S(═O)2—NR2OR21;
• —C(═O)—OR22;
• —C(═O)—R23;
• —S(═O)—R24;
• —S(═O)2—R24;
• —C(═NH)—NH2;
• —C(═NH)—NH—R27;
• —N═C(NH2)2;
• —N═C(NH R28)(NHR29);
• denotes a linear or branched, saturated or unsaturated aliphatic C1-10 residue, which is in each case substituted with optionally 1, 2, 3, 4, 5, 6, 7, 8 or 9 substituents mutually independently selected from the group consisting of —CN, —NO2, —OH, —NH2, —SH, —O(C1-5 alkyl), —S(C1-5 alkyl), —NH(C1-5 alkyl), —N(C1-5 alkyl)(C1-5 alkyl), —OCF3 and —SCF3;
• denotes an unsubstituted C2-10 alkenyle residue or an unsubstituted C2-10 alkynyle residue;
• denotes an unsaturated or saturated, unsubstituted or at least monosubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-membered cycloaliphatic residue optionally comprising at least one heteroatom as a ring member, which residue is in each case attached to the parent structure via a carbon atom in the ring of the cycloaliphatic residue and may be fused with a saturated or unsaturated, unsubstituted or at least monosubstituted mono- or polycyclic ring system and/or be attached via a linear or branched, unsubstituted or at least monosubstituted C1-6 alkylene group;
• or denotes an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, which may be fused with a saturated or unsaturated, unsubstituted or at least monosubstituted mono- or polycyclic ring system and/or be attached via a linear or branched, unsubstituted or at least monosubstituted C1-6 alkylene group;
• R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R27, R28 and R29, mutually independently, in each case denote a linear or branched, saturated or unsaturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• denote an unsaturated or saturated, unsubstituted or at least monosubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-membered cycloaliphatic residue optionally comprising at least one heteroatom as a ring member, which residue may be fused with a saturated or unsaturated, unsubstituted or at least monosubstituted mono- or polycyclic ring system and/or be attached via a linear or branched, unsubstituted or at least monosubstituted C1-6 alkylene group or 2- to 6-membered heteroalkylene group;
• or denote an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, which may be fused with a saturated or unsaturated, unsubstituted or at least monosubstituted mono- or polycyclic ring system and/or be attached via a linear or branched, unsubstituted or at least monosubstituted C1-6 alkylene group or 2- to 6-membered heteroalkylene group;
• or
• R12 and R13, in each case together with the nitrogen atom joining them together as a ring member, form a saturated or unsaturated, unsubstituted or at least monosubstituted 4-, 5-, 6-, 7-, 8- or 9-membered heterocycloaliphatic residue optionally comprising at least one further heteroatom as ring member, which may be fused with a saturated or unsaturated, unsubstituted or at least monosubstituted mono- or polycyclic ring system;
• and
• R25 and R26, mutually independently, in each case denote a hydrogen residue;
• denote a linear or branched, saturated or unsaturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• or denote an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, which may be fused with a saturated or unsaturated, unsubstituted or at least monosubstituted mono- or polycyclic ring system and/or be attached via a linear or branched, unsubstituted or at least monosubstituted C1-6 alkylene group or C2-6 alkenylene group or C2-6 alkynylene group;
• or denote an unsaturated or saturated, unsubstituted or at least monosubstituted, 3-, 4-, 5-, 6-, 7-, 8- or 9-membered cycloaliphatic residue optionally comprising at least one heteroatom as a ring member;
• providing that R25 and R26 do not in each case denote a hydrogen residue;
• or
• R25 and R26, together with the carbon atom joining them together as a ring member, form a saturated or unsaturated, unsubstituted or at least monosubstituted 3-, 4-, 5- or 6-membered cycloaliphatic residue;
• and R30, R31 and R32, mutually independently, in each case
• denote a linear or branched, saturated or unsaturated, unsubstituted or at least monosubstituted aliphatic C1-10 residue;
• in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts or in each case in the form of corresponding solvates.