RU2001126547A

RU2001126547A - Biphenyl derivatives

Info

Publication number: RU2001126547A
Application number: RU2001126547/04A
Authority: RU
Inventors: Мишель БОЭ; Гуидо Галлей; Тирри Годель; Торстен Хоффманн; Вальтер Хункелер; Патрик Шнидер; Хайнц Штадлер
Original assignee: Ф.Хоффманн - Ля Рош АГ
Priority date: 1999-03-09
Filing date: 2000-02-28
Publication date: 2003-09-20

Claims

1. Compounds of the general formula

in which R represents a hydrogen atom, C ₁ -C ₇ alkyl, C ₁ -C ₇ alkoxy, a halogen atom, an amino group, —N (R ⁶ ) ₂ or trifluoromethyl;

R ¹ represents a hydrogen atom, a C ₁ -C ₇ alkoxy or a halogen atom;

R and R ¹ may together form —CH = CH — CH═CH—;

R ² represents a halogen atom, C ₁ -C ₇ alkyl or trifluoromethyl;

R ³ represents a hydrogen atom or C ₁ -C ₇ alkyl;

R ⁴ represents a hydrogen atom or a cyclic tertiary amine optionally substituted with C ₁ -C ₇ alkyl;

R ⁵ represents a hydrogen atom, a nitro, amino group or —N (R ⁶ ) ₂ ;

R ⁶ represents a hydrogen atom or C ₁ -C ₇ alkyl;

X is —C (O) N (R ⁶ ) -, - (CH ₂ ) _n O—, - (CH ₂ ) _n N (R ⁶ ) -, —N (R ⁶ ) C (O) -, or —N (R ⁶ ) (CH ₂ ) _n -;

n is 1 or 2;

and their pharmaceutically acceptable acid addition salts, with the exception of the following compounds:

N - [(4-methylphenyl) methyl] hydrochloride (1,1’-diphenyl) -2-methanamine and

N - {[4- (1,1-dimethylethyl) phenyl] methyl} -N-methylhydrochloride (1,1’-diphenyl) -2-methanamine.

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

3. The compound according to claim 2, which is a

(3,5-bistrifluoromethylbenzyl) 2’-methyldiphenyl-2-carboxylic acid methylamide,

(3,5-bistrifluoromethylbenzyl) methylamide 2’-methyl-5- (4-methylpiperazin-1-yl) diphenyl-2-carboxylic acid or

(3,5-bistrifluoromethylbenzyl) methylamide 2’-chloro-5- (4-methylpiperazin-1-yl) diphenyl-2-carboxylic acid.

4. The compound according to claim 1, wherein X is —N (R ⁶ ) C (O) -, and R ⁶ is methyl.

5. The compound according to claim 4, which is a

2- (3,5-bistrifluoromethyl-phenyl) -N-methyl-N- (2’-methyl-4-nitrodiphenyl-2-yl) isobutyramide,

N- (4-amino-2’-methyldiphenyl-2-yl) -2- (3,5-bistrifluoromethylphenyl) -N-methylisobutyramide,

2- (3,5-bistrifluoromethylphenyl) -N-methyl-N- (2’-methyl-4-methylaminodiphenyl-2-yl) isobutyramide,

2- (3,5-bistrifluoromethylphenyl) -N-methyl-N- (2’-methyldiphenyl-2-yl) iso-butyramide or

N- (2’-aminodiphenyl-2-yl) -2- (3,5-bistrifluoromethylphenyl) -N-methylisobutyramide.

6. A medicament comprising one or more compounds according to any one of claims 1 to 5 and pharmaceutically acceptable excipients.

7. The drug according to claim 6 for the treatment of diseases associated with NK-1 receptor antagonists.

8. The method of obtaining the compounds of formula 1 according to claim 1, which includes a) the reaction of a compound of the formula with a compound of the formula

with a compound of the formula

to obtain a compound of the formula

in which R ¹ -R ⁶ , R and n have the meanings specified in claim 1, or

b) the reaction of the compounds of formula

with a compound of the formula

to obtain a compound of the formula

in which R ¹ -R ⁶ , R and n have the meanings specified in claim 1, or

c) reduction of a compound of the formula

to the compound of the formula

in which the substituents have the meanings indicated in claim 1, or

g) the reaction of the compounds of formula

with a compound of the formula

to obtain a compound of the formula

in which the substituents have the meanings indicated in claim 1, or

d) the reaction of the compounds of formula

with a compound of the formula

to obtain a compound of the formula

in which the substituents have the meanings indicated in claim 1, or

e) reduction of a compound of the formula

to the compound of the formula

in which the substituents have the meanings indicated in claim 1, or

g) the reaction of the compounds of formula

with a compound of the formula

to obtain a compound of the formula

in which the substituents have the meanings indicated above, or

h) methylation of the compounds of formula

to the compound of the formula

in which the substituents have the meanings indicated above, or

i) the reaction of the compounds of formula

with a compound of the formula

to obtain a compound of the formula

in which the substituents have the meanings indicated above, or

k) modifying one or more substituents R ¹ -R ⁶ or R within the above definitions and, if necessary, converting the resulting compound into a pharmaceutically acceptable acid addition salt.

9. The compound according to any one of claims 1 to 5, obtained according to the method according to claim 8 or an equivalent method.

10. The use of a compound according to any one of claims 1 to 5 in the treatment of diseases associated with the NK-1 receptor.

11. The use of the compounds of formula I according to any one of claims 1 to 5 for the preparation of medicines, including one or more compounds of formula 1, in the treatment of diseases associated with the NK-1 receptor.

12. The invention as described above.