Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy

1. Phenalkylamine derivatives of the formula (I)

wherein

R is R 1 —W-A 1 -Q-Y-A 2 -X 1 —;

R 1 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 6 -alkyl, tri(C 1 -C 4 -alkyl)-silyl-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylcarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkyloxycarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylaminocarbonylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylaminocarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylsulfonylamino-C 1 -C 4 -alkyl, (optionally substituted C 6 -C 12 -aryl-C 1 -C 6 -alkyl)amino-C 1 -C 4 -alkyl, optionally substituted C 6 -C 12 -aryl-C 1 -C 4 -alkyl, optionally substituted C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkyl, C 3 -C 12 -cycloalkyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, halogenated C 1 -C 6 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, aminocarbonyl, C 1 -C 6 -alkylaminocarbonyl, (halogenated C 1 -C 4 -alkyl)aminocarbonyl, C 6 -C 12 -arylaminocarbonyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkoxy, halogenated C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, amino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylamino-C 1 -C 4 -alkoxy, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylcarbonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -arylcarbonylamino-C 1 -C 4 -alkoxy, C 1 -C 6 -alkoxycarbonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -aryl-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylsulfonylamino-C 1 -C 4 -alkoxy, (halogenated C 1 -C 6 -alkyl)sulfonylamino-C 1 -C 4 -alkoxy, C 6 -C 12 -arylsulfonylamino-C 1 -C 4 -alkoxy, (C 6 -C 12 -aryl-C 1 -C 6 -alkyl)sulfonylamino-C 1 -C 4 -alkoxy, C 3 -C 12 -heterocyclylsulfonylamino-C 1 -C 4 -alkoxy, C 3 -C 12 -heterocyclyl-C 1 -C 4 -alkoxy, C 6 -C 12 -aryloxy, C 3 -C 12 -heterocyclyloxy, C 1 -C 6 -alkylthio, halogenated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylamino, (halogenated C 1 -C 6 -alkyl)amino, di-C 1 -C 6 -alkylamino, di-(halogenated C 1 -C 6 -alkyl)amino, C 1 -C 6 -alkylcarbonylamino, (halogenated C 1 -C 6 -alkyl)carbonylamino, C 6 -C 12 -arylcarbonylamino, C 1 -C 6 -alkylsulfonylamino, (halogenated C 1 -C 6 -alkyl)sulfonylamino, C 6 -C 12 -arylsulfonylamino or optionally substituted C 3 -C 12 -heterocyclyl;

W is —NR 8 — or a bond;

A 1 is optionally substituted C 1 -C 4 -alkylene or a bond;

Q is —S(O) 2 —;

Y is —NR 9 —;

A 2 is optionally substituted C 1 -C 4 -alkylene, C 1 -C 4 -alkylene-CO—, —CO—C 1 -C 4 -alkylene, C 1 -C 4 -alkylene-O—C 1 -C 4 -alkylene, C 1 -C 4 -alkylene-NR 10 —C 1 -C 4 -alkylene, optionally substituted C 2 -C 4 -alkenylene, optionally substituted C 2 -C 4 -alkynylene, optionally substituted C 6 -C 12 -arylene, optionally substituted C 6 -C 12 -heteroarylene or a bond;

X 1 is —O—, —NR 11 —, —S—, optionally substituted C 1 -C 4 -alkylene, optionally substituted C 2 -C 4 -alkenylene, or optionally substituted C 2 -C 4 -alkynylene;

R 2 is hydrogen, halogen, C 1 -C 6 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, —CN, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkoxy, halogenated C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxycarbonyl, C 2 -C 6 -alkenyloxy, C 6 -C 12 -aryl-C 1 -C 4 -alkoxy, C 1 -C 6 -alkylcarbonyloxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, aminosulfonyl, amino, C 1 -C 6 -alkylamino, C 2 -C 6 -alkenylamino, nitro or optionally substituted C 3 -C 12 -heterocyclyl, or two radicals R 2 together with the ring atoms to which they are bound form a 5- or 6 membered ring;

R 3 is hydrogen or C 1 -C 6 -alkyl;

X 2 is —O—, —NR 6 —, —S—, >CR 12a R 12b or a bond;

X 3 is —O—, —NR 7 —, —S—, >CR 13a R 13b or a bond;

R 5 is optionally substituted C 6 -C 12 -aryl, optionally substituted C 3 -C 12 -cycloalkyl or optionally substituted C 3 -C 12 -heterocyclyl;

Y 1 is >CR 14a R 14b or a bond;

Y 2 is >CR 15a R 15b or a bond;

R 4a is hydrogen, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, CH 2 CN, C 6 -C 12 -aryl-C 1 -C 4 -alkyl, C 3 -C 12 -cycloalkyl, —CHO, C 1 -C 4 -alkylcarbonyl, (halogenated C 1 -C 4 -alkyl)carbonyl, C 6 -C 12 -arylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, C 1 -C 6 -alkylaminocarbonyl, C 2 -C 6 -alkenyl, —C(═NH)NH 2 , —C(═NH)NHCN, C 1 -C 6 -alkylsulfonyl, C 6 -C 12 -arylsulfonyl, amino, —NO or C 3 -C 12 -heterocyclyl; or

R 4a , R 3

together are optionally substituted C 1 -C 6 -alkylene; or

R 4a , R 14a

together are optionally substituted C 1 -C 6 -alkylene;

R 4b is hydrogen, C 1 -C 6 -alkyl, halogenated C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, C 3 -C 12 -cycloalkyl, CH 2 CN, —CHO, C 1 -C 4 -alkylcarbonyl, (halogenated C 1 -C 4 -alkyl)carbonyl, C 6 -C 12 -arylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, C 1 -C 6 -alkylaminocarbonyl, C 2 -C 6 -alkenyl, —C(═NH)NH 2 , —C(═NH)NHCN, C 1 -C 6 -alkylsulfonyl, C 6 -C 12 -arylsulfonyl, amino, —NO or C 3 -C 12 -heterocyclyl; or

R 4a , R 4b

together are optionally substituted C 1 -C 6 -alkylene, wherein one —CH 2 — of C 1 -C 6 -alkylene may be replaced by an oxygen atom or —NR 16 ; or

R 6 is hydrogen or C 1 -C 6 -alkyl;

R 7 is hydrogen or C 1 -C 6 -alkyl;

R 8 is hydrogen or C 1 -C 6 -alkyl;

R 9 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl, amino-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl-C 1 -C 4 -alkyl or C 3 -C 12 -heterocyclyl; or

R 9 , R 1

together are C 1 -C 4 -alkylene; or

R 9 is C 1 -C 4 -alkylene that is bound to a carbon atom in A 2 and A 2 is C 1 -C 4 -alkylene or to a carbon atom in X 1 and X 1 is C 1 -C 4 -alkylene;

R 10 is hydrogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkylsulfonyl;

R 11 is hydrogen or C 1 -C 6 -alkyl, or

R 9 , R 11

together are C 1 -C 4 -alkylene,

R 12a is hydrogen, optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, C 3 -C 12 -heterocyclyl-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl or hydroxy;

R 12b is hydrogen or C 1 -C 6 -alkyl, or

R 12a , R 12b

together are carbonyl or optionally substituted C 1 -C 4 -alkylene, wherein one —CH 2 — of C 1 -C 4 -alkylene may be replaced by an oxygen atom or —NR 17 —;

R 13a is hydrogen, optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, C 3 -C 12 -heterocyclyl-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl or hydroxy;

R 13b is hydrogen or C 1 -C 6 -alkyl, or

R 13a , R 13b

together are carbonyl or optionally substituted C 1 -C 4 -alkylene, wherein one —CH 2 — of C 1 -C 4 -alkylene may be replaced by an oxygen atom or —NR 18 —;

R 14a is hydrogen, optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, C 3 -C 12 -heterocyclyl-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl or hydroxy;

R 14b is hydrogen or C 1 -C 6 -alkyl, or

R 14a , R 14b,

together are carbonyl or optionally substituted C 1 -C 4 -alkylene, wherein one or two —CH 2 — of C 1 -C 4 -alkylene may be replaced by an oxygen atom or —NR 19 —;

R 15a is hydrogen, optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, C 3 -C 12 -heterocyclyl-C 1 -C 6 -alkyl, optionally substituted C 6 -C 12 -aryl or hydroxy;

R 15b is hydrogen or C 1 -C 6 -alkyl, or

R 15a , R 15b

together are carbony or optionally substituted C 1 -C 4 -alkylene, wherein one or two —CH 2 — of C 1 -C 4 -alkylene may be replaced by an oxygen atom or —NR 19 —;

R 16 is hydrogen or C 1 -C 6 -alkyl;

R 17 is hydrogen or C 1 -C 6 -alkyl;

R 18 is hydrogen or C 1 -C 6 -alkyl, and

R 19 is hydrogen or C 1 -C 6 -alkyl,

or a physiologically tolerated salt thereof.

2. The compound of claim 1 , wherein —Y-A 2 -X 1 — comprises at least 2, 3 or 4 atoms in the main chain.

3. The compound of claim 1 , wherein R 1 is C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, di-C 1 -C 6 -alkylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkyloxycarbonylamino-C 1 -C 4 -alkyl, C 1 -C 6 -alkylaminocarbonylamino-C 1 -C 4 -alkyl, C 6 -C 12 -aryl-C 1 -C 4 -alkyl, C 3 -C 12 -cycloalkyl, C 2 -C 6 -alkenyl, optionally substituted C 6 -C 12 -aryl, hydroxy, C 1 -C 6 -alkylamino, (halogenated C 1 -C 6 -alkyl)amino, di-C 1 -C 6 -alkylamino or optionally substituted C 3 -C 12 -heterocyclyl.

4. The compound of claim 1 , wherein A 1 is a bond, or A 1 is C 1 -C 4 -alkylene and W is —NR 8 —.

5. The compound of claim 1 , wherein A 2 is C 1 -C 4 -alkylene, or A 2 is C 6 -C 12 -arylene selected from the group consisting of phen-1,4-ylene and phen-1,3-ylene, or C 6 -C 12 -heteroarylene selected from the group consisting of pyrid-2,5-ylene and pyrid-2,4-ylene.

6. The compound of claim 1 , wherein X 1 is —O— or —NR 11 , or X 1 is optionally substituted C 1 -C 4 -alkylene and A 2 is a bond, or X 1 is optionally substituted C 2 -C 4 -alkynylene and A 2 is a bond.

7. The compound of claim 1 , wherein R 1 —W-A 1 -Q-Y-A 2 -X 1 — is R 1 —S(O) 2 —NH-A 2 -X 1 —.

8. The compound of claim 1 , having one of the formulae

wherein R 1 , W, A 1 , Q, Y, A 2 , X 1 , R 2 , R 3 , X 2 , X 3 , R 5 , Y 1 , Y 2 , R 4a , R 4b are as defined in claim 1 .

9. The compound of claim 1 , wherein X 2 is CR 12a R 12b and X 3 is a bond.

10. The compound of claim 1 , wherein R 12a is hydrogen or C 1 -C 6 -alkyl and R 12b is hydrogen or C 1 -C 6 -alkyl, or R 12a , R 12b together are optionally substituted C 1 -C 4 -alkylene.

11. The compound of claim 1 , having the formula

wherein R 20a , R 20b , R 20c , R 20d , R 20e independently are hydrogen, halogen, optionally substituted C 1 -C 6 -alkyl, halogenated C 1 -C 6 -alkyl, CN, hydroxy, C 1 -C 6 -alkoxy, amino, C 1 -C 6 -alkylamino, di-C 1 -C 6 -alkylamino or C 3 -C 12 -heterocyclyl.

12. The compound of claim 1 , wherein Y 1 is a bond and Y 2 is >CR 15a R 15b , or Y 1 is a bond and Y 2 is a bond.

13. The compound of claim 1 , wherein R 4a is hydrogen, C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 4 -alkyl, amino-C 1 -C 4 -alkyl, CH 2 CN, C 6 -C 12 -aryl-C 1 -C 4 -alkyl, C 3 -C 12 -cycloalkyl, —CHO, C 1 -C 4 -alkylcarbonyl, (halogenated C 1 -C 4 -alkyl)carbonyl, C 6 -C 12 -arylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 6 -C 12 -aryloxycarbonyl, —C(═NH)NH 2 , —C(═NH)NHCN, C 1 -C 6 -alkylsulfonyl, amino, —NO or C 3 -C 12 -heterocyclyl, or R 4a , R 3 together are optionally substituted C 1 -C 4 -alkylene, or R 4a , R 14a together are optionally substituted C 1 -C 4 -alkylene.

14. The compound of claim 1 , wherein R 4b is hydrogen or C 1 -C 6 -alkyl.

15. The compound of claim 1 , wherein R 4a , R 4b together are optionally substituted C 1 -C 6 -alkylene, wherein one —CH 2 — of C 1 -C 4 -alkylene may be replaced by an oxygen atom.

16. The compound of claim 1 , wherein

R is R 1 —W-A 1 -Q-Y-A 2 -X 1 —;

R 1 is C 1 -C 6 -alkyl, C 3 -C 12 -cycloalkyl-C 1 -C 4 -alkyl, halogenated C 1 -C 6 -alkyl, or optionally substituted C 3 -C 12 -heterocyclyl;

W is a bond;

A 1 is a bond;

Q is —S(O) 2 —;

Y is —NR 9 —;

A 2 is C 1 -C 4 -alkylene or a bond;

X 1 is —O— or optionally substituted C 1 -C 4 -alkylene;

R 2 is hydrogen or halogen;

R 3 is hydrogen;

Y 1 is a bond;

Y 2 is >CR 15a R 15b or a bond;

R 4a is hydrogen, C 1 -C 6 -alkyl, C 6 -C 12 -aryl-C 1 -C 4 -alkyl, or C 1 -C 4 -alkoxycarbonyl; or

R 4a , R 3

together are optionally substituted C 1 -C 6 -alkylene,

R 4b is hydrogen, C 1 -C 6 -alkyl, halogenated C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, (halogenated C 1 -C 4 -alkyl)carbonyl or C 1 -C 4 -alkoxycarbonyl; or

R 4a , R 4b

together are optionally substituted C 1 -C 6 -alkylene, wherein one —CH 2 — of C 1 -C 6 -alkylene may be replaced by an oxygen atom;

X 2 is CR 12a R 12b ;

X 3 is a bond;

R 5 is optionally substituted phenyl;

R 9 is hydrogen or C 1 -C 6 -alkyl;

R 12a is hydrogen; and

R 12b is hydrogen; or

R 12a , R 12b

together are optionally substituted C 1 -C 4 -alkylene;

R 15a is hydrogen; and

R 15b is hydrogen; or

R 15a , R 15b

together are carbonyl.

17. in the compound of claim 1 , which is:

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(2-amino-1-benzyl-ethyl)-4-fluoro-phenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid (2-{3-[2-amino-1-(3-chloro-benzyl)-ethyl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[5-(2-amino-1-benzyl-ethyl)-2-fluoro-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[5-(2-amino-1-benzyl-ethyl)-2-fluoro-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(2-amino-1-benzyl-ethyl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(2-amino-1-benzyl-ethyl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid (2-{3-[2-amino-1-(3,5-difluoro-benzyl)-ethyl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid (2-{3-[2-amino-1-(4-chloro-benzyl)-ethyl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[2-amino-1-(3-chloro-benzyl)-ethyl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid (2-{3-[2-amino-1-(3-trifluoromethyl-benzyl)-ethyl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[2-amino-1-(3,5-difluoro-benzyl)-ethyl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[2-amino-1-(3-trifluoromethyl-benzyl)-ethyl]-phenoxy}-ethyl)-amide;

2-[3-(Cyclopropylmethanesulfonylamino-methyl)-phenyl]-3-phenyl-propionamide;

N-[3-(2-Amino-1-benzyl-ethyl)-benzyl]-C-cyclopropyl-methanesulfonamide;

2-{3-[(1-Methyl-1H-pyrazole-4-sulfonylamino)-methyl]-phenyl}-3-phenyl-propionamide;

2-{3-[(1-Methyl-1H-imidazole-4-sulfonylamino)-methyl]-phenyl}-3-phenyl-propionamide;

1-Methyl-1H-imidazole-4-sulfonic acid 3-(1-benzyl-2-morpholin-4-yl-2-oxo-ethyl)benzylamide;

1-Methyl-1H-pyrazole-4-sulfonic acid 3-(2-amino-1-benzyl-ethyl)-benzylamide;

1-Methyl-1H-imidazole-4-sulfonic acid 3-(2-amino-1-benzyl-ethyl)-benzylamide;

1-Methyl-1H-imidazole-4-sulfonic acid 3-(1-benzyl-2-morpholin-4-yl-ethyl)-benzylamide;

1-Methyl-1H-pyrazole-4-sulfonic acid 3-(1-benzyl-2-morpholin-4-yl-ethyl)-benzylamide;

N-[3-(1-Benzyl-2-morpholin-4-yl-ethyl)-benzyl]-C-cyclopropyl-methanesulfonamide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(1-benzyl-2-dimethylamino-ethyl)-4-fluorophenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(1-benzyl-2-dimethylamino-ethyl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(1-benzyl-2-dimethylamino-ethyl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid 3-(1-benzyl-2-dimethylamino-ethyl)-benzylamide;

1-Methyl-1H-pyrazole-4-sulfonic acid 3-(1-benzyl-2-dimethylamino-ethyl)-benzylamide;

1-Methyl-1H-pyrazole-4-sulfonic acid (2-{3-[2-dimethylamino-1-(3-trifluoromethyl-benzyl)ethyl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[2-dimethylamino-1-(3-trifluoromethylbenzyl)-ethyl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(1-benzyl-2-dimethylamino-ethyl)-4-chlorophenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[5-(1-benzyl-2-dimethylamino-ethyl)-2-fluorophenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[5-(1-benzyl-2-dimethylamino-ethyl)-2-fluorophenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(1-benzyl-2-dimethylamino-ethyl)-4-fluorophenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(1-benzyl-2-pyrrolidin-1-yl-ethyl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(1-benzyl-2-pyrrolidin-1-yl-ethyl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(2-azetidin-1-yl-1-benzyl-ethyl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid 3-(2-azetidin-1-yl-1-benzyl-ethyl)-benzylamide;

Propane-1-sulfonic acid [2-(3-{benzylamino-[1-(4-chloro-phenyl)-cyclobutyl]-methyl}-phenoxy)-ethyl]-amide;

tert-Butyl {2-[1-(4-chlorophenyl)cyclobutyl]-2-[3-({methyl[(1-methyl-1H-pyrazol-4-yl)sulfonyl]amino}methyl)phenyl]ethyl}carbamate;

tert-Butyl {2-[1-(4-chlorophenyl)cyclobutyl]-2-(3-{[methyl(propylsulfonyl)amino]methyl}phenyl)ethyl}carbamate;

tert-Butyl {2-[1-(4-chlorophenyl)cyclobutyl]-2-[3-({methyl[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}methyl)phenyl]ethyl}carbamate;

N-(3-{2-amino-1-[1-(4-chlorophenyl)cyclobutyl]ethyl}benzyl)-N-methylpropane-1-sulfonamide;

N-(3-{2-amino-1-[1-(4-chlorophenyl)cyclobutyl]ethyl}benzyl)-3-fluoro-N-methylpropane-1-sulfonamide;

N-(3-{2-amino-1-[1-(4-chlorophenyl)cyclobutyl]ethyl}benzyl)-N,1-dimethyl-1H-imidazole-4-sulfonamide;

N-(3-{2-amino-1-[1-(4-chlorophenyl)cyclobutyl]ethyl}benzyl)-N,1-dimethyl-1H-pyrazole-4-sulfonamide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(3-benzyl-azetidin-3-yl)-phenoxy]-ethyl}-amide;

3-Benzyl-3-{3-[2-(1-methyl-1H-imidazole-4-sulfonylamino)-ethoxy]-phenyl}-azetidine-1-carboxylic acid ethyl ester;

3-Benzyl-3-[3-(2-cyclopropylmethanesulfonylamino-ethoxy)-phenyl]-azetidine-1-carboxylic acid ethyl ester;

N-{2-[3-(3-Benzyl-azetidin-3-yl)-phenoxy]-ethyl}-C-cyclopropyl-methane sulfonamide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(3-benzyl-azetidin-3-yl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(3-benzyl-azetidin-3-yl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[5-(3-benzyl-1-methyl-azetidin-3-yl)-2-fluorophenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[5-(3-benzyl-1-methyl-azetidin-3-yl)-2-fluorophenoxy]-ethyl}-methyl-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[3-benzyl-1-(2,2,2-trifluoro-ethyl)-azetidin-3-yl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[3-benzyl-1-(2,2-difluoro-ethyl)-azetidin-3-yl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(3-benzyl-5-oxo-pyrrolidin-3-yl)-phenoxy]-ethyl}-amide;

N-{2-[3-(3-Benzyl-5-oxo-pyrrolidin-3-yl)-phenoxy]-ethyl}-C-cyclopropyl-methanesulfonamide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(3-benzyl-5-oxo-pyrrolidin-3-yl)-phenoxy]-ethyl}-amide;

N-{2-[3-(3-Benzyl-pyrrolidin-3-yl)-phenoxy]-ethyl}-C-cyclopropyl-methanesulfonamide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(3-benzyl-pyrrolidin-3-yl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(3-benzyl-pyrrolidin-3-yl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(3-benzyl-1-methyl-piperidin-3-yl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3-(3-benzyl-1-methyl-piperidin-3-yl)-phenoxy]-ethyl}-amide;

N-{2-[3-(3-Benzyl-1-methyl-piperidin-3-yl)-phenoxy]-ethyl}-C-cyclopropyl-methanesulfonamide;

1-Methyl-1H-imidazole-4-sulfonic acid 3-(3-benzyl-5-oxo-pyrrolidin-3-yl)-benzylamide;

1-Methyl-1H-pyrazole-4-sulfonic acid 3-(3-benzyl-5-oxo-pyrrolidin-3-yl)-benzylamide;

1-Methyl-1H-pyrazole-4-sulfonic acid 3-(3-benzyl-pyrrolidin-3-yl)-benzylamide;

N-[3-(3-Benzyl-pyrrolidin-3-yl)-benzyl]-C-cyclopropyl-methanesulfonamide;

1-Methyl-1H-pyrazole-4-sulfonic acid 3-(3-benzyl-1-methyl-pyrrolidin-3-yl)-benzylamide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(3-benzyl-1-methyl-pyrrolidin-3-yl)-phenoxy]-ethyl}-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[3-benzyl-1-(2,2-difluoro-acetyl)-pyrrolidin-3-yl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[3-benzyl-1-(2-fluoro-ethyl)-azetidin-3-yl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[3-benzyl-1-(2-methoxy-ethyl)-azetidin-3-yl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(3-benzyl-1-methyl-pyrrolidin-3-yl)-phenoxy]-ethyl}-methyl-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[3-benzyl-1-(2-fluoro-ethyl)-pyrrolidin-3-yl]-phenoxy}-ethyl)-amide;

1-Methyl-1H-imidazole-4-sulfonic acid (2-{3-[3-benzyl-1-(2,2-dimethyl-propyl)-pyrrolidin-3-yl]-phenoxy}-ethyl)-amide; or

1-Methyl-1H-imidazole-4-sulfonic acid {2-[3-(3-benzyl-1-isopropyl-pyrrolidin-3-yl)phenoxy]-ethyl}-amide;

or a physiologically tolerated salt thereof.

18. A pharmaceutical composition comprising a carrier and a compound of claim 1 .