Substituted 2-[2-(phenyl) ethylamino] alkaneamide derivatives and their use as sodium and/or calcium channel modulators

1. A compound of formula (I):

wherein:

X is —O—;

Y is hydrogen, —OH or —O(C 1 -C 4 )alkyl;

Z is ═O or ═S;

R is —(C 3 -C 10 )alkyl; ω-trifluoro(C 3 -C 10 )alkyl;

R 1 and R 2 are, independently, hydrogen, hydroxy, —(C 1 -C 8 )alkoxy, —(C 1 -C 8 ) alkylthio, halo, trifluoromethyl or 2,2,2-trifluorethyl; or one of R 1 and R 2 is ortho to R—X— and, taken together with the same R—X—, represents a

group where R 0 is —(C 2 -C 9 )alkyl;

R 3 and R′ 3 are, independently, hydrogen or —(C 1 -C 4 )alkyl;

R 4 and R 5 are, independently, hydrogen, —(C 1 -C 4 )alkyl; or R 4 is hydrogen and R 5 is

—CH 2 —OH, —CH 2 —O—(C 1 -C 6 )alkyl, —CH(CH 3 )—OH, —(CH 2 ) 2 —S—CH 3 , benzyl or 4-hydroxybenzyl; or R 4 and R 5 , taken together with the adjacent carbon atom, form a —(C 3 -C 6 )cycloalkyl residue;

R 6 and R 7 are independently hydrogen or —(C 1 -C 6 )alkyl; or taken together with the adjacent nitrogen atom form a 5- or 6-membered monocyclic saturated heterocycle, optionally containing —O—, —S— or —NR 8 , wherein R 8 is hydrogen or —(C 1 -C 6 )alkyl;

its pharmaceutically acceptable salts and the isolated optical isomers or mixtures of optical isomers of the compound and their pharmaceutically acceptable salts.

2. The compound of claim 1 wherein:

X is —O—;

Y is hydrogen, —OH or —O(C 1 -C 3 )alkyl;

Z is ═O or ═S;

R is —(C 4 -C 7 )alkyl or ω-trifluoro(C 4 -C 6 )alkyl;

R 1 and R 2 are, independently, hydrogen, —(C 1 -C 4 )alkoxy, halo, trifluoromethyl or 2,2,2-trifluorethyl; or one of R 1 and R 2 is ortho to R—X— and, taken together with the same R—X—, represents a

group where R 0 is —(C 2 -C 5 )alkyl;

R 3 and R′ 3 are, independently, hydrogen or —(C 1 -C 3 )alkyl;

R 4 and R 5 are, independently, hydrogen or —(C 1 -C 4 )alkyl; or R 4 is hydrogen and R 5 is —CH 2 —OH, —CH 2 —O—(C 1 -C 3 )alkyl, —(CH 2 ) 2 —S—CH 3 , benzyl or 4-hydroxybenzyl;

R 6 and R 7 are, independently, hydrogen or —(C 1 -C 4 )alkyl; or taken together with the adjacent nitrogen atom form a 5- or 6-membered monocyclic saturated heterocycle, optionally containing —O— or —NR 8 —, wherein R 8 is hydrogen or —(C 1 -C 3 )alkyl;

its pharmaceutically acceptable salts and the isolated optical isomers or mixtures of optical isomers of the compound and their pharmaceutically acceptable salts.

3. The compound of claim 1 wherein:

X is —O—;

Y is hydrogen, or —O(C 1 -C 3 )alkyl;

Z is ═O or ═S;

R is —(C 4 -C 7 )alkyl or ω-trifluoro(C 4 -C 6 )alkyl;

R 1 and R 2 are, independently, hydrogen, —(C 1 -C 3 )alkoxy, fluoro, chloro, trifluoromethyl or 2,2,2-trifluorethyl; or one of R 1 and R 2 is ortho to R—X— and, taken together with the same R—X—, represents a

group where R 0 is —(C 3 -C 4 )alkyl;

R 3 and R′ 3 are, independently, hydrogen or —(C 1 -C 3 )alkyl;

R 4 and R 5 are, independently, hydrogen or —(C 1 -C 4 )alkyl; or R 4 is hydrogen and R 5 is —CH 2 —OH, —CH 2 —O—(C 1 -C 3 )alkyl, benzyl or 4-hydroxybenzyl;

R 6 and R 7 are, independently, hydrogen or —(C 1 -C 3 )alkyl; or taken together with the adjacent nitrogen atom form a 5- or 6-membered monocyclic saturated heterocycle, optionally containing —O— or —NR 8 —, wherein R 8 is hydrogen or —(C 1 -C 3 )alkyl;

its pharmaceutically acceptable salts and the isolated optical isomers or mixtures of optical isomers of the compound and their pharmaceutically acceptable salts.

4. The compound of claim 1 wherein:

X is —O—;

Y is hydrogen;

Z is ═O;

R is —(C 4 -C 6 )alkyl;

R 1 and R 2 are, independently, hydrogen or halo;

R 3 , R′ 3 , R 4 and R 5 are hydrogen;

R 6 and R 7 are, independently, hydrogen or —(C 1 -C 3 )alkyl;

its pharmaceutically acceptable salts and the isolated optical isomers or mixtures of optical isomers of the compound and their pharmaceutically acceptable salts.

5. The compound of claim 1 wherein said compound is selected from the group consisting of:

2-[2-(3-Butoxyphenyl)-ethylamino]-acetamide;

2-[2-(3-Pentyloxyphenyl)-ethylamino]-acetamide;

2-[2-(3-Hexyloxyphenyl)-ethylamino]-acetamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-N-methylacetamide;

2-[2-(3-Pentyloxyphenyl)-ethylamino]-N-methylacetamide;

2-[2-(3-Hexyloxyphenyl)-ethylamino]-N-methylacetamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxyphenyl)-(N′-hydroxy)ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxyphenyl)-(N′-methoxy)ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxyphenyl)-(N′-propoxy)ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-dimethyl-thioacetamide;

2-[2-(3-Butoxyphenyl)-2-methylpropylamino]-N,N-dimethylacetamide;

2-{2-[3-(4,4,4-Trifluorobutoxyl)phenyl]-ethylamino}-N,N-dimethylacetamide;

2-[2-(3-Butoxy-2-chlorophenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxy-2-fluorophenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxy-4-methoxyphenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-diethylacetamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-dipropylacetamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-dibutylacetamide;

2-[2-(3-Pentyloxyphenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Hexyloxyphenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-1-pyrrolidin-1-yl-ethan-1-one;

2-[2-(3-Pentyloxyphenyl)-ethylamino]-1-pyrrolidin-1-yl-ethan-1-one;

2-[2-(3-Hexyloxyphenyl)-ethylamino]-1-pyrrolidin-1-yl-ethan-1-one;

2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-3-hydroxy-N,N-dimethylpropanamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-3-methoxy-N,N-dimethylpropanamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-3-propoxy-N,N-dimethylpropanamide;

2-[2-(3-Butoxyphenyl)-ethylamino]-2-N,N-trimethylpropanamide;

2-[2-(3-Pentyloxyphenyl)-ethylamino]-2-N,N-trimethylpropanamide;

2-[2-(3-Hexyloxyphenyl)-ethylamino]-2-N,N-trimethylpropanamide;

(S)-2-[2-(3-Butoxyphenyl)-ethylamino]-propanamide;

(S)-2-[2-(3-Butoxyphenyl)-ethylamino]-N-methylpropanamide;

(S)-2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide;

(R)-2-[2-(3-Butoxyphenyl)-ethylamino]-propanamide;

(R)-2-[2-(3-Butoxyphenyl)-ethylamino]-N-methylpropanamide;

(R)-2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide;

2-[2-(3-Butoxy-2-trifluoromethylphenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxy-4-trifluoromethylphenyl)-ethylamino]-N,N-dimethylacetamide; and

2-[2-(3-Butoxy-5-trifluoromethylphenyl)-ethylamino]-N,N-dimethylacetamide;

its pharmaceutically acceptable salts and the isolated optical isomers or mixtures of optical isomers of the compound and their pharmaceutically acceptable salts.

6. The compound of claim 5 , wherein said compound is a hydrochloric or methanesulfonic acid salt thereof.

7. The compound of claim 1 wherein said compound is selected from the group consisting of:

2-[2-(3-Butoxyphenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Butoxy-2,6-difluorophenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-Pentyloxyphenyl)-ethylamino]-N,N-dimethylacetamide;

2-[2-(3-hexyloxyphenyl)-ethylamino]-N,N-dimethylacetamide; and its pharmaceutically acceptable salts.

8. The compound of claim 7 , wherein said compound is a hydrochloric or methanesulfonic acid salt thereof.

9. The compound of claim 1 , wherein said compound is 2-[2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylacetamide or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9 , wherein said compound is a hydrochloric or methanesulfonic acid salt thereof.

11. The compound of claim 1 , wherein

Y is —OH or —O(C 1 -C 4 )alkyl; or

Z is ═S; or

R is —(C 9 -C 10 )alkyl or ω-trifluoro(C 3 -C 10 )alkyl; or

R 1 and/or R 2 are not hydrogen; or

both R 3 and R′ 3 are not hydrogen; or

both R 4 and R 5 are not hydrogen and do not form a —(C 3 -C 6 )cycloalkyl residue when taken together with the adjacent carbon atom; or

R 6 and R 7 taken together with the adjacent nitrogen atom form a monocyclic 5- or 6-membered saturated heterocycle, optionally containing —O—, —S— or NR 8 —, wherein R 8 is hydrogen or —(C 1 -C 6 )alkyl;

its pharmaceutically acceptable salts and the isolated optical isomers or mixtures of optical isomers of the compound and their pharmaceutically acceptable salts.

12. A pharmaceutical composition comprising the compound of claim 1 .

13. The pharmaceutical composition of claim 12 , further comprising pharmaceutically acceptable and therapeutically inert organic or inorganic carrier materials.