Bos, Michael; Galley, Guido; Godel, Thierry; Hoffmann, Torsten; Hunkeler, Walter; Schnider, Patrick; Stadler, Heinz;

Biphenyl derivatives

The invention relates to compounds of the formula ##STR1## wherein R is hydrogen, lower alkyl, lower alkoxy halogen, amino, --N(R.sup.6).sub.2 or trifluoromethyl; R.sup.1 is hydrogen lower alkoxy or halogen, R and R.sup.1 may be together --CH.dbd.CH--CH.dbd.CH--; R.sup.2 is halogen, lower alkyl or trifluoromethyl; R.sup.3 is hydrogen or lower alkyl; R.sup.4 is hydrogen or a cyclic tertiary amine, optionally substituted by lower alkyl; R.sup.5 is hydrogen, nitro, amino or --N(R.sup.6).sub.2 ; R.sup.6 is hydrogen or lower alkyl, X is --C(O)N(R.sup.6)--, --(CH.sub.2).sub.n O--, (CH.sub.2).sub.n N(R.sup.6)--, --N(R.sup.6)C(O)-- or --N(R.sup.6)(CH.sub.2).sub.n --; and n is 1 or 2; and pharmaceutically acceptable acid addition salts thereof. The compounds of formula I may be used for the treatment of diseases related to the NK-1 receptor.

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What is claimed is:

1. A compound of the formula ##STR67##

wherein

R is hydrogen, lower alkyl, lower alkoxy, halogen, amino, --N(R.sup.6).sub.2 or trifluoromethyl;

R.sup.1 is hydrogen, lower alkoxy or halogen;

R and R.sup.1 may be together --CH.dbd.CH--CH.dbd.CH--;

R.sup.2 is trifluoromethyl;

R.sup.3 is hydrogen or lower alkyl;

R.sup.4 is hydrogen or a cyclic tertiary amine, optionally substituted by lower alkyl;

R.sup.5 is hydrogen, nitro, amino or --N(R.sup.6).sub.2 ;

R.sup.6 is hydrogen or lower alkyl;

X is --C(O)N(R.sup.6)-- or --N(R.sup.6)C(O)--; and

n is 1 or 2;

or pharmaceutically acceptable acid addition salts thereof.

2. A compound according to claim 1, wherein X is --C(O)N(R.sup.6)-- and R.sup.6 is methyl.

3. A compound according to claim 2, 2'-methyl-biphenyl-2-carboxylic acid-(3,5-bis-trifluoromethyl-benzyl)-methyl-amide.

4. A compound according to claim 2, 2'-methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid-(3,5-bis-trifluoromethyl-benzyl)-methyl-amide.

5. A compound according to claim 2, 2'-chloro-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid-(3,5-bis-trifluoromethyl-benzyl)-methyl-amide.

6. A compound according to claim 1, wherein X is --N(R.sup.6)--CO-- and R.sup.6 is methyl.

7. A compound according to claim 6, 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(2'-methyl-4-nitro-biphenyl- 2-yl)-isobutyramide.

8. A compound according to claim 6, N-(4-amino-2'-methyl-biphenyl-2-yl)-2-(3,5-bis-trifluoromethyl-phenyl)-N-m ethyl-isobutyramide.

9. A compound according to claim 6, 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(2'-methyl-4-methylamino-bip henyl-2-yl)-isobutyramide.

10. A compound according to claim 6, 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(2'-methyl-biphenyl-2-yl)-is obutyramide.

11. A compound according to claim 6, N-(2'-amino-biphenyl-2-yl)-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-iso butyramide.

12. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I in accordance with claim 1 and a pharmaceutically acceptable carrier.