Substituted Phenylureas and Phenylamides as Vanilloid Receptor Ligands

A compound corresponding to formula (Q)

• wherein
• R101, R102 and R103 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, CH2—OH, CH2CH2—OH, CH2—OCH3, CH2CH2—OCH3, OCFH2, OCF2H, OCF3, OH, NH2, a C1-4 alkyl, an O—C1-4 alkyl, a NH—C1-4 alkyl, and a N(C1-4 alkyl)2, wherein the C1-4 alkyl is in each case unsubstituted;
• R2 represents CF3, an unsubstituted C1-4 alkyl or an unsubstituted C3-6 cycloalkyl;
• R7 and R9 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, OH, OCF3, a C1-4 alkyl, and an O—C1-4 alkyl, wherein the C1-4 alkyl is in each case unsubstituted;
• A denotes N, CH or C(CH3);
• p denotes 0 or 1;
• R115 represents H or a C1-6 alkyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of OH and OCH3;
• B denotes C(R116a)(R116b), wherein
• R116a is selected from the group consisting of H, CH3, CH2OH and OH, and
• R116b is selected from the group consisting of H, CH3 and CH2OH,
• with the proviso that R116a is not OH, when R115 represents H;
• or
• R116a and R116b together with the carbon atom connecting them form an unsubstituted C3-6 cycloalkyl or an unsubstituted 3 to 6 membered heterocyclyl, wherein at least one ring member of the heterocyclyl is selected from the group consisting of O, S, N, NH and N(C1-4 alkyl);
• or
• B denotes C(R116c)(R116d)—C(R117a)(R117b), wherein
• R116c is selected from the group consisting of H, CH3, CH2OH and OH, and
• R116d is selected from the group consisting of H, CH3 and CH2OH;
• or
• R116c and R116d together with the carbon atom connecting them form an unsubstituted C3-6 cycloalkyl or an unsubstituted 3 to 6 membered heterocyclyl, wherein at least one ring member of the heterocyclyl is selected from the group consisting of O, S, N, NH and N(C1-4 alkyl);
• R117a is selected from the group consisting of H, CH3, CH2OH and OH, and
• R117b is selected from the group consisting of H, CH3 and CH2OH,
• with the proviso that R117a is not OH, when R115 represents H;
• or
• R117a and R117b together with the carbon atom connecting them form an unsubstituted C3-6 cycloalkyl or an unsubstituted 3 to 6 membered heterocyclyl, wherein at least one ring member of the heterocyclyl is selected from the group consisting of O, S, N, NH and N(C1-4 alkyl);
• in the form of a free compound or a physiologically acceptable salt thereof, and if appropriate, in the form of an individual stereoisomer or a mixture of stereoisomers.

A compound corresponding to formula (R)

• wherein
• R101, R102 and R103 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, CH2—OH, CH2CH2—OH, CH2—OCH3, CH2CH2—OCH3, OCFH2, OCF2H, OCF3, OH, NH2, a C1-4 alkyl, an O—C1-4 alkyl, a NH—C1-4 alkyl, and a N(C1-4 alkyl)2, wherein the C1-4 alkyl is in each case unsubstituted;
• R2 represents CF3, an unsubstituted C1-4 alkyl or an unsubstituted C3-6 cycloalkyl;
• R7 and R9 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, OH, OCF3, a C1-4 alkyl, and an O—C1-4 alkyl, wherein the C1-4 alkyl is in each case unsubstituted;
• A denotes N, CH or C(CH3);
• q denotes 0, 1 or 2;
• R112 represents H or a C1-4 alkyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, OH, ═O and OCH3;
• R113 represents a H, S(═O)2—NH2, a C1-4 alkyl or a S(═O)2—C1-4 alkyl, wherein the C1-4 alkyl is in each case unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, OH, ═O and OCH3;
• or, if q is not 0, then
• R112 and R113 together with the nitrogen atom connecting them form a 3 to 6 membered heterocyclyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, CN, CF3, CH3, CH2CH3, CH(CH3)2, tert.-butyl, cyclopropyl, OH, ═O, OCH3, OCF3, NH2, NH(CH3) and N(CH3)2;
• in the form of a free compound or a physiologically acceptable salt thereof, and if applicable, in the form of an individual stereoisomer or a mixture of stereoisomers.

A compound corresponding to formula (S)

• wherein
• R101, R102 and R103 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, CH2—OH, CH2CH2—OH, CH2—OCH3, CH2CH2—OCH3, OCFH2, OCF2H, OCF3, OH, NH2, C1-4 alkyl, O—C1-4 alkyl, NH—C1-4 alkyl, and a N(C1-4 alkyl)2, wherein the C1-4 alkyl is in each case unsubstituted;
• R2 represents CF3, an unsubstituted C1-4 alkyl or an unsubstituted C3-6 cycloalkyl;
• R7 and R9 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, OH, OCF3, C1-4 alkyl, and O—C1-4 alkyl, wherein the C1-4 alkyl is in each case unsubstituted;
• A denotes N, CH or C(CH3);
• R109 and R110 together with the nitrogen atom connecting them form a 3 to 10 membered heterocyclyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, CN, CF3, CH2OH, CH2CH2OH, CH3, CH2CH3, CH(CH3)2, tert.-butyl, cyclopropyl, OH, ═O, OCH3, OCF3, NH2, NH(CH3) and N(CH3)2;
• in the form of a free compound or a physiologically acceptable salt thereof, and if applicable, in the form of an individual stereoisomer or a mixture of stereoisomers.

A compound corresponding to formula (T)

• wherein
• R101, R102 and R103 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, CH2—OH, CH2CH2—OH, CH2—OCH3, CH2CH2—OCH3, OCFH2, OCF2H, OCF3, OH, NH2, C1-4 alkyl, O—C1-4 alkyl, NH—C1-4 alkyl, and N(C1-4 alkyl)2, wherein the C1-4 alkyl is in each case unsubstituted,
• R2 represents CF3, unsubstituted C1-4 alkyl or unsubstituted C3-6 cycloalkyl;
• R7 and R9 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, OH, OCF3, C1-4 alkyl, and O—C1-4 alkyl, wherein the C1-4 alkyl is in each case unsubstituted;
• A denotes N, CH or C(CH3);
• t denotes 0, 1 or 2;
• and
• R108 represents C1-4 alkyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, OH, ═O and OCH3;
• in the form of a free compound or a physiologically acceptable salt thereof, and if applicable, in the form of an individual stereoisomer or a mixture of stereoisomers.

A compound corresponding to formula (U)

• wherein
• R101, R102 and R103 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, CH2—OH, CH2CH2—OH, CH2—OCH3, CH2CH2—OCH3, OCFH2, OCF2H, OCF3, OH, NH2, C1-4 alkyl, O—C1-4 alkyl, NH—C1-4 alkyl, and N(C1-4 alkyl)2, wherein the C1-4 alkyl is in each case unsubstituted;
• R2 represents CF3, unsubstituted C1-4 alkyl or unsubstituted C3-6 cycloalkyl;
• R7 and R9 are each independently selected from the group consisting of H, F, Cl, Br, CFH2, CF2H, CF3, CN, OH, OCF3, C1-4 alkyl, and O—C1-4 alkyl, wherein the C1-4 alkyl is in each case unsubstituted;
• A denotes N, CH or C(CH3);
• R104 represents
• H, or C1-4 alkyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, NH2, NH(CH3), N(CH3)2, ═O, OH and OCH3;
• OR105, wherein
• R105 represents H or C1-4 alkyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, NH2, NH(CH3), N(CH3)2, ═O, OH and OCH3;
• or
• NR106R107, wherein
• R106 represents H or C1-4 alkyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, NH2, NH(CH3), N(CH3)2, ═O, OH and OCH3, and
• R107 is selected from the group consisting of:
• H, or C1-4 alkyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, NH2, NH(CH3), N(CH3)2, ═O, OH and OCH3;
• C3-6 cycloalkyl or a 3 to 6 membered heterocyclyl, which is in each case unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, CF3, CH3, CH2CH3, CH(CH3)2, tert.-butyl, cyclopropyl, OH, ═O, OCH3, OCF3, NH2, NH(CH3) and N(CH3)2, and wherein at least one ring member of the heterocyclyl is selected from the group consisting of O, S, N, NH and N(C1-4 alkyl);
• phenyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, CN, CF3, CH3, CH2CH3, CH(CH3)2, tert.-butyl, cyclopropyl, NH2, NH(CH3), N(CH3)2, OH, OCF3 and OCH3;
• and
• heteroaryl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, CN, CF3, CH3, CH2CH3, CH(CH3)2, tert.-butyl, cyclopropyl, NH2, NH(CH3), N(CH3)2, OH, OCF3 and OCH3;
• or wherein
• R106 and R107 together with the nitrogen atom connecting them form a 3 to 6 membered heterocyclyl, which is unsubstituted or mono-, di- or trisubstituted with 1, 2 or 3 substituents independently selected from the group consisting of F, Cl, Br, CF3, CH3, CH2CH3, CH(CH3)2, tert.-butyl, cyclopropyl, OH, ═O, OCH3, OCF3, NH2, NH(CH3) and N(CH3)2;
• in the form of a free compound or a physiologically acceptable salt thereof, and if appropriate in the form of an individual stereoisomer or a mixture of stereoisomers.