IP Library › Granted Patent US 8,193,179

Granted Patent B2

US 8,193,179 · App. 12/664,828 · Granted Jun 5, 2012

3-amino-6-(1-amino-ethyl)-tetrahydropyran derivatives

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Quick Facts

Patent No.: US 8,193,179
App. No.: 12/664,828
Granted: Jun 5, 2012
Kind: B2

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Abstract

Antibacterial compounds including 3-amino-6-(1-amino-ethyl)-tetrahydropyran derivatives are provided, and methods of treatment or prevention of bacterial infection with such compounds are provided.

Claims (108)

1. A compound of formula I

wherein

R 1 represents halogen or alkoxy;

U and W each represent N, V represents CH and R 2 represents H or F, or

U and V each represent CH, W represents N and R 2 represents H or F, or

U represents N, V represents CH, W represents CH or CR a and R 2 represents H, or also,

when W represents CH, may represent F;

R a represents CH 2 OH or alkoxycarbonyl;

A represents the group CH═CH—B, a binuclear heterocyclic system D, a phenyl group which is mono substituted in position 4 by a (C 1 -C 4 )alkyl group, or a phenyl group which is disubstituted in positions 3 and 4, wherein each of the two substituents is independently selected from (C 1 -C 4 )alkyl or halogen;

B represents a mono- or di-substituted phenyl group wherein each substituent is a halogen atom;

D represents the group

wherein

Z represents CH or N, and

Q represents O or S;

or a salt of the compound.

2. The compound of formula I according to claim 1 , wherein if U represents N and V represents CH then W represents CR a and R 2 represents H;

or a salt of the compound.

3. The compound of formula I according to claim 1 ,

wherein

R 1 represents halogen or (C 1 -C 4 )alkoxy;

R a represents CH 2 OH or [(C 1 -C 4 )alkoxy]carbonyl; and

B represents a di-substituted phenyl group wherein each substituent is a halogen atom;

or a salt of the compound.

4. The compound of formula I according to claim 3 , wherein U represents N, V represents CH, W represents CR a and R 2 represents H;

or a salt of the compound.

5. The compound of formula I according to claim 1 , wherein R 1 is (C 1 -C 4 )alkoxy;

or a salt of the compound.

6. The compound of formula I according to claim 1 , wherein A represents the group CH═CH—B;

or a salt of the compound.

7. The compound of formula I according to claim 1 , wherein A represents a binuclear heterocyclic system D;

or a salt of the compound.

8. The compound of formula I according to claim 1 , wherein A represents a phenyl group which is mono substituted in position 4 by a (C 1 -C 4 )alkyl group, or a phenyl group which is disubstituted in positions 3 and 4, wherein each of the two substituents is independently selected from (C 1 -C 4 )alkyl or halogen;

or a salt of the compound.

9. The compound of formula I according to claim 1 , wherein the compound is:

{(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-yl}-[3-(E)-(2,5-difluoro-phenyl)-allyl]amine;

{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-yl}-[3-(E)-(2,5-difluoro-phenyl)-allyl]amine;

{(3R,6S)-6-[(1R)-1-amino-2-(6-fluoro-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-yl}-[(E)-3-(2,5-difluoro-phenyl)-allyl]amine;

{(3R,6S)-6-[(1S)-1-amino-2-(6-fluoro-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-yl}-[(E)-3-(2,5-difluoro-phenyl)-allyl]amine;

6-({(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

{(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy-quinolin-4-yl)-ethyl]tetrahydro-pyran-3-yl}-[3-(E)-(2,5-difluoro-phenyl)-allyl]-amine;

{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-quinolin-4-yl)-ethyl]tetrahydro-pyran-3-yl}-[3-(E)-(2,5-difluoro-phenyl)-allyl]-amine;

6-({(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3R,6S)-6-[(1 S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

8-[(2R)-2-amino-2-{5-[(E)-3-(2,5-difluoro-phenyl)-allylamino]-tetrahydro-pyran-2-yl}-ethyl]-2-methoxy-quinoline-5-carboxylic acid methyl ester;

8-[(2S)-2-amino-2-{5-[(E)-3-(2,5-difluoro-phenyl)-allylamino]-tetrahydro-pyran-2-yl}-ethyl]-2-methoxy-quinoline-5-carboxylic acid methyl ester;

8((S)-2-amino-2-{(2S,5R)-5-[(E)-3-(2,5-difluoro-phenyl)-allylamino]-tetrahydro-pyran-2-yl}-ethyl)-2-methoxy-quinolin-5-yl]-methanol;

8((R)-2-amino-2-{(2S,5R)-5-[(E)-3-(2,5-difluoro-phenyl)-allylamino]-tetrahydro-pyran-2-yl}-ethyl)-2-methoxy-quinolin-5-yl]-methanol;

6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

{3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]tetrahydro-pyran-3-yl}-(4-ethyl-benzyl)-amine;

{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-quinolin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-benzo[1,4]oxazin-3-one;

6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-yl}-(3-fluoro-4-methyl-benzyl)-amine;

{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-benzo[1,4]oxazin-3-one;

6-({(3S,6R)-6-[(1R)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3S,6R)-6-[(1S)-1-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3S,6R)-6-[(1R)-1-amino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-ethyl]tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

6-({(3S,6R)-6-[(1S)-1-amino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-ethyl]tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

6-({(3S,6R)-6-[(1R)-1-amino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-ethyl]tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3S,6R)-6-[(1S)-1-amino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-ethyl]tetrahydro-pyran-3-ylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;

6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-benzo[1,4]oxazin-3-one; or

6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-tetrahydro-pyran-3-ylamino}-methyl)-4H-benzo[1,4]oxazin-3-one;

or a salt of the compound.

10. The compound according to claim 9 , wherein the compound is: