Antibacterial agents
Naphthyridine and related derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof,
wherein:
Z 1 , Z 3 , and Z 4 are independently N or CR 1a ;
Z 2 , Z 5 , and Z 6 are each CR 1a ;
A is CR 2 R 3 ;
R 1 and R 1a are independently at each occurrence hydrogen; cyano; halo; hydroxy; (C 1-6 )alkoxy;
R 2 is hydrogen; halo; hydroxy; or (C 1-6 )alkoxy;
R 3 is hydrogen;
R 8 is hydrogen; halo; hydroxyl; or (C 1-6 )alkyl;
R 11 is hydrogen, (C 1-6 )alkyl, (C 1-6 )alkoxycarbonyl, or (C 1-6 )alkylcarbonyl;
R 12 is UR 13 ;
U is CH 2 ; C(═O); or SO 2 ;
R 13 is a substituted or unsubstituted heterocyclic ring system (A):
X is O or S
R 15 is at each occurrence independently hydrogen; (C 1-4 )alkyl; (C 1-4 )alkoxy; halo or trifluoromethyl.
2. A compound according to claim 1 , wherein:
Z 1 and Z 4 are N; and
Z 3 is CR 1a .
3. A compound according to claim 1 , wherein:
R 1 is OCH 3 .
4. A compound according to claim 1 , wherein:
R 1a is at each occurrence independently hydrogen; halogen; or cyano.
5. A compound according to claim 4 , wherein: R 15 is hydrogen.
6. A compound or a pharmaceutically acceptable salt thereof, wherein the compound is selected from group consisting of
3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-8-oxa-3-azabicyclo[3.2.1]oct-6-yl)amino]methyl}-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one;
6-{[((1R,5R,6R)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-8-oxa-3-azabicyclo[3.2.1]oct-6-yl)amino]methyl}-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one;
6-{[((1R,5R,6S)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-8-oxa-3-azabicyclo[3.2.1]oct-6-yl)amino]methyl}-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one; and
6-{[((1R,5R,6R)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-8-oxa-3-azabicyclo[3.2.1]oct-6-yl)amino]methyl}-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one.
7. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
8. A method of treating bacterial infections due to Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Haemophilus influenzae, Moraxella catarrhalis or Escherichia coil in mammals which comprises administering to a mammal in need thereof an effective amount of a compound of claim 1 .