NK1 antagonists

A compound having the formula (I):

• or the pharmaceutically acceptable salts or solvates thereof, wherein:
• Ar1 and Ar2 are each independently:
• X1 is selected from the group consisting of —O—, —S—, —SO—, —SO2—, —NR20—, —N(COR20)— and —N(SO2R17)—;
• and
• when X1 is selected from the group consisting of —SO—, —SO2—, —N(COR20)— and —N(SO2R17)—, then R1 and R2 are each independently selected from the group consisting of H, C1-C6 alkyl, hydroxy(C1-C3 alkyl)-, C3-C8 cycloalkyl, —CH2F, —CHF2 and —CF3;
• or R1 and R2, together with the carbon atom to which they are both attached, form a C3-C8 cycloalkyl ring;
• and
• when X1 is selected from the group consisting of —O—, —S— and —NR20—, then R1 and R2 are each independently selected from the group consisting of H, C1-C8 alkyl, hydroxy(C1-C3 alkyl)-, C3-C8 cycloalkyl, —CH2F, —CHF2 and —CF3;
• or R1 and R2, together with the carbon atom to which they are both attached, form a C3-C6 cycloalkyl group;
• or R1 and R2, together with the carbon atom to which they are both attached, form a —C(═O) group;
• R3 is selected from the group consisting of H, C1-C6 alkyl, hydroxy(C1-C3 alkyl)-, C3-C8 cycloalkyl, —CH2F, —CHF2 and —CF3;
• R4 and R5 are each independently selected from the group consisting of H, C1-C6 alkyl-, -halogen, —OR20, —O—C(O)NR15R16, —NR15R16, —NR15SO2R17, —NR15C(O)R14, —NR20C(O)NR15R16 and —SR20;
• or R4 and R5, together with the carbon atom to which they are both attached, form a —C(═O)— or —C(═NR13)— group;
• R6 and R7, taken together with the carbon atom to which they are bound, form:
• (a) a 5-membered heterocycloalkyl ring;
• or
• (b) a 5-membered heterocycloalkenyl ring;
• wherein said 5-membered heterocycloalkyl ring or said 5-membered heterocycloalkenyl ring each comprise 3 carbon atoms and 2 heteroatoms independently selected from the group consisting of:
• N═, and —NR20— (wherein R20 is defined below), and said 5-membered heterocycloalkyl ring or said 5-membered heterocycloalkenyl ring are each optionally substituted with from 1 to 4 R45 substituents wherein each R45 substituent is independently selected;
• R8 and R9 are each independently selected from the group consisting of H, C1-C6 alkyl-, halogen, —OR20, —O—C(O)NR15R16, —NR15R16, —NR15SO2R17, —NR15C(O)R14, —NR20C(O)NR15R16 and —SR20;
• or R8 and R9, taken together with the carbon atom to which they are both attached, form a —C(═O)— group;
• R10, R11 and R12 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C8 cycloalkyl, —OR20, halogen, —CN, —NO2, —CF3, —CHF2, —CH2F, —CH2CF3, —OCF3, —OCHF2, —OCH2F, —OCH2CF3, —C(O)OR20, —C(O)NR23R24, —NR23C(O)R20, —NR23CO2R17, —NR23C(O)NR23R24, —NR23SO2R17, —NR23R24, —SO2NR23R24, —S(O)n5R17, aryl, and aryl substituted with (R21)r wherein each R21 substitutent is independently selected;
• each R13 is independently selected from the group consisting of —OH and —O—(C1-C6 alkyl);
• each R14 is independently selected from the group consisting of H, C1-C6 alkyl, C3-C8 cycloalkyl, —C1-C6 alkylNH2 and —C1-C6 alkylNHC(O)OC1-C6 alkyl;
• R15 and R16 are each independently selected from the group consisting of H, benzyl, C1-C6 alkyl, and C3-C8 cycloalkyl;
• each R17 is independently selected from the group consisting of C1-C5 alkyl, C3-C8 cycloalkyl and —CF3;
• each R20 is independently selected from the group consisting of H, C1-C6 alkyl, C3-C8 cycloalkyl, —(C1-C6)alkylNH2, (C1-C6)alkoxy(C2-C6)alkyl, and hydroxy(C2-C6)alkyl;
• each R21 is a substituent on the aryl ring to which it is attached and is independently selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, —OH, -halogen, —CN, —NO2, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —O—(C1-C6 alkyl), —O—(C3-C8 cycloalkyl), —C(O)OR20, —C(O)NR23R24, —NR23R24, —NR23C(O)R20, —NR23CO2R20, —NR23C(O)NR23R24, —NR23SO2R17 and —S(O)n5R17;
• R23 and R24 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C8 cycloalkyl and benzyl;
• R30 and R31 are each independently selected from the group consisting of H, C1-C6 alkyl (e.g., C1-C2 alkyl), —CH2F, —CHF2, —CF3, —OH, and —O(C1 to C3)alkyl;
• or R30 and R31, together with the carbon atom to which they are both attached, form a —C(═O)— group;
• each R45 is independently selected from the group consisting of:
• C1-C6 alkyl (e.g., C1-O2 alkyl), —CH2F, —CHF2, —CF3, —OH, and —O(C1 to C3)alkyl;
• or two R45 substituents, together with the carbon atom to which they are both attached, form a —C(═O)— group;
• r is from 1 to 3;
• n4 is from 0 to 3;
• n5 is from 0 to 2;
• and
• n8 is from 0 to 4.