Neurokinin antagonists for use as medicaments

A compound having the formula

• 158
• wherein:
• R1a is H, NR9R10, —OR10, Cl, Br,
• 159
• R1b and R1c are independently H or —OR9, or R1b and R1c together are ═O, ═CH2 or —OCH2CH2O—;
• R2 is H, oxo, —OR9 or —CH3;
• R3, R4, R5, R6, R7 and R8 are each independently selected from H, cyano, nitro, trifluoromethoxy, trifluoromethyl, C1-6alkylsulfonyl, halo, —OR9, —OCH2O—, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, —C(═O)OR9, —C(═O)NR9R10, —OC(═O)R9, —NR9C(═O)R10, aminosulfonyl and C1-6alkyl substituted by any of the hereinabove substituents;
• wherein at least two of R3, R4, R5, R6, R7 and R8 are H;
• R9 is independently selected from H, C1-6alkyl, C1-4alkoxy, and —OCH2(CH2)nphenyl;
• R10 is independently H or C1-6alkyl, hydroxyC1-6alkyl, (NR9R9)C1-6alkyl, (NR9R9)C(═O)C1-6alkyl, —(CH2)oR15;
• R11 is phenyl, substituted in at least the ortho position by C1-6alkylthio, C1-6alkylsulfinyl, C1-6alkylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl, C1-6alkanesulfonamido, C1-6alkanoyl, C1-6alkoxy-carbonyl, succinamido, carbamoyl, C1-6alkylcarbamoyl, di-C1-6alkylcarbamoyl, C1-6alkoxy-C1-6alkylcarbamoyl, N-methylcarbamoyl, C1-6alkanoylamino, ureido, C1-6ureido, di-C1-6alkylureido, amino, C1-6alkylamino, or di-C1-6alkylamino;
• R12 is selected from hydrogen, hydroxy, C1-6alkoxy, C1-6alkanoyloxy, C1-6alkanoyl, C1-6alkoxycarbonyl, C1-6alkanoylamino, C1-6alkyl, carbamoyl, C1-6alkylcarbamoyl and bis(C1-6alkyl)carbamoyl;
• R13 is —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—;
• R14 is hydrogen, hydroxy, C1-6alkoxy, C1-6alkanoyloxy, C1-6alkanoyl, C1-6alkoxycarbonyl, C1-6alkanoylamino, C1-6alkyl, carbamoyl, C1-6alkylcarbamoyl or di-C1-6alkylcarbamoyl;
• R15 is a 5- or 6-membered saturated or unsaturated heterocycle containing 1 or 2 heteroatoms selected from nitrogen, oxygen and sulfur and additionally subsituted with 0 or 1 oxo groups;
• or R15 is phenyl substituted by 0, 1, or 2 substitutents selected from halogen, C1-4alkoxy, vicinal-methylenedioxy, —S(═O)nC1-4alkyl, —S(═O)2NH2 and C1-4alkyl;
• M is —C(═O)— or —S(═O)2—;
• L is —NH— or —CH2—;
• X1 and X2 are independently H or halogen, wherein at least one of X1 and X2 are halogen;
• Y and Z are independently selected from CH2, O, S, S═O and S(═O)2, wherein at least one of Y and Z is CH2;
• n is independently, at each instance, 0 or 1;
• o is independently, at each instance, 1, 2 or 3;
• and
• any pharmaceutically-acceptable salt thereof.