4-(1-amino-ethyl)-cyclohexylamine derivatives
View Patent ↗The invention relates to compounds of formula (I) wherein R 0 represents H or OH; R 1 represents alkoxy; U and W represent N, V represents CH and R 2 represents H or F, or U and V represent CH, W represents N and R 2 represents H or F, or U and V represent N, W represents CH and R 2 represents H, or U represents N, V represents CH, W represents CR a and R 2 represents H; R a represents CH 2 OH or alkoxycarbonyl; A represents the group CH═CH—B or a binuclear heterocyclic system D, B representing a mono- or di-substituted phenyl group wherein the substituents are halogen atoms and D representing one of the following groups wherein Z represents CH or N, and Q represents O or S; and to salts of such compounds. These compounds are useful as antibacterial agents.
1. A compound of formula I
wherein
R 0 represents H or OH;
R 1 represents alkoxy;
U and W represent N, V represents CH and R 2 represents H or F
A represents the group CH═CH—B or a binuclear heterocyclic system D;
B represents a mono- or di-substituted phenyl group wherein the substituents are halogen atoms;
D represents either the group
wherein
the sign * designates the point of attachment of the group to the rest of the molecule,
Z represents CH or N, and
Q represents O or S,
or the group
wherein the sign * designates the point of attachment of the group to the rest of the molecule;
or a pharmaceutically acceptable salt of such a compound.
2. A compound of formula I according to claim 1 , which is also a compound of formula I p ;
wherein
R 1 represents alkoxy;
U and W represent N, V represents CH and R 2 represents H or F;
A represents the group CH═CH—B or a binuclear heterocyclic system D;
B represents a mono- or di-substituted phenyl group wherein the substituents are halogen atoms;
D represents the group
wherein
the sign * designates the point of attachment of the group to the rest of the molecule,
Z represents CH or N, and
Q represents O or S;
or a pharmaceutically acceptable salt of such a compound.
3. A compound of formula I according to claim 1 , wherein R 1 represents methoxy;
or a pharmaceutically acceptable salt of such a compound.
4. A compound of formula I according to claim 1 , which is:
6-(trans-{4-[(1R)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-(trans-{4-[(1S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-(trans-{4-[(1R*,2R*)-1-amino-2-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
trans-{4-[1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-cyclohexyl}-[3-(2,5-difluoro-phenyl)-allyl]-amine;
6-(trans-{4-[1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
trans-6-({4-[1-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
cis-6-({-4-[1-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
trans-(1R*,2R*)-2-amino-2-{4-[(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-cyclohexyl}-1-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol;
trans-(1R*,2R*)-2-amino-2-{4-[(E)-3-(2,5-difluoro-phenyl)-allylamino]-cyclohexyl}-1-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol;
or a pharmaceutically acceptable salt of one of these compounds.
5. A pharmaceutical composition comprising a compound of formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.
6. A compound of formula I according to claim 1 , wherein A represents the group CH═CH—B wherein B represents a mono- or di-substituted phenyl group wherein the substituents are halogen atoms;
or a pharmaceutically acceptable salt of such a compound.
7. A compound of formula I according to claim 1 , wherein A represents the group
wherein
the sign “*” designates the point of attachment of the group to the rest of the molecule,
Z represents CH or N, and
Q represents O or S;
or a pharmaceutically acceptable salt of such a compound.
8. A compound of formula I according to claim 1 , wherein A represents the group
wherein the sign “*” designates the point of attachment of the group to the rest of the molecule;
or a pharmaceutically acceptable salt of such a compound.