Heterocyclic compounds useful as anti-bacterial agents and method for production thereof

10912,780

16/487317

June 08, 2018

The present disclosure relates to compounds of Formula I, or their stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms and pharmaceutically active derivatives thereof, and pharmaceutical compositions containing them as the active ingredient which can be used as medicaments. The aforementioned substances can also be used in the manufacture of medicaments for treatment, prevention or suppression of diseases, and conditions mediated by microbes. The present disclosure also relates to the synthesis and characterization of aforementioned substances. [chemical expression included]

Bugworks Research, Inc. (Wilmington, DE, US)

Bugworks Research, Inc. (Wilmington, DE, US)

1. A compound of Formula I [chemical expression included] or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, wherein R 1 is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, C 1-6 alkylamino, C 1-6 aminoalkylene, and 4-7 membered carbocyclyl or heterocyclyl ring which may be fully saturated or unsaturated or partially unsaturated optionally having up to three heteroatoms independently selected from O, N, and S, each of which is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, amino, hydroxyl, C 1-6 alkoxy, SO 3 H, SO 2 R 9 , COORS, CONHR 9 , and SO 2 NHR 9 , wherein R 9 is selected from H, C 1-6 alkyl, methylsulfone, C 1-6 alkyl, OC 1-6 alkyl, OC 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7 membered heterocyclyl ring which may be fully saturated or unsaturated or partially unsaturated optionally having up to three heteroatoms independently selected from O, N, and S, C 3-6 cycloalkylamino, C 3-6 aminocycloalkyl, C 1-6 alkylamino, and di (C 1-6 alkyl)amino; R 2 and R 3 are independently selected from the group consisting of hydrogen, C 1-6 alkyl, fluorine, OC 1-6 alkyl, hydroxyl, and amino; R is selected from the group consisting of hydrogen, fluorine, cyano, OC 1-6 alkyl, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is CH or C—C 1-6 alkyl when dotted line () represents a bond, wherein R 6 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with hydroxyl, or amino; or X 4 is selected from the group consisting of CH 2 and O; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; n 2 is 0 to 2; Y 2 and Y 3 are independently selected from N and CR 7 ; R 7 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; Z 1 is selected from the group consisting of O, S, and CH 2 ; and R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and fluorine.

2. A compound as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, wherein R 1 is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, C 1-6 alkylamino, C 1-6 aminoalkylene, and 4-7 membered carbocyclyl or heterocyclyl ring which may be fully saturated or unsaturated or partially unsaturated optionally having up to three heteroatoms independently selected from O, N, and S, each of which is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, amino, hydroxyl, C 1-6 alkoxy, SO 3 H, SO 2 R 9 , COORS, CONHR 9 , and SO 2 NHR 9 , wherein R 9 is selected from H, C 1-6 alkyl, methylsulfone, OC 1-6 alkyl, OC 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7 membered heterocyclyl ring which may be fully saturated or unsaturated or partially unsaturated optionally having up to three heteroatoms independently selected from O, N, and S, C 3-6 cycloalkylamino, C 3-6 aminocycloalkyl, C 1-6 alkylamino, and di(C 1-6 alkyl)amino; R 2 and R 3 are selected from the group consisting of hydrogen, fluorine, methoxy, hydroxyl, and amino; provided that at least one of R 2 and R 3 is hydrogen; R is selected from the group consisting of hydrogen, fluorine, methoxy, cyano, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is CH, or C—C 1-6 alkyl wherein dotted line () represents a bond; R 6 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with hydroxyl or amino; X 4 is selected from the group consisting of CH 2 and O; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; n 2 is 0 to 2; Y 2 and Y 3 are independently selected from —N and CR 7 ; R 7 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; Z 1 is selected from the group consisting of O, S, and CH 2 ; and R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and fluorine.

3. A compound as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms and pharmaceutically active derivatives thereof, wherein R 1 is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, C 1-6 alkylamino, C 1-6 aminoalkylene, and 4-7 membered carbocyclyl or heterocyclyl ring which may be fully saturated or unsaturated or partially unsaturated optionally having up to three heteroatoms independently selected from O, N, and S, each of which is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, amino, hydroxyl, C 1-6 alkoxy, SO 3 H, SO 2 R 9 , COORS, CONHR 9 , and SO 2 NHR 9 , wherein R 9 is selected from H, C 1-6 alkyl, methylsulfone, C 1-6 alkyl, OC 1-6 alkyl, OC 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7 membered heterocyclyl ring which may be fully saturated or unsaturated or partially unsaturated optionally having up to three heteroatoms independently selected from O, N, and S, C 3-6 cycloalkylamino, C 3-6 aminocycloalkyl, C 1-6 alkylamino, and di(C 1-6 alkyl)amino; R 2 and R 3 are independently selected from the group consisting of hydrogen, hydroxyl, fluorine, methyl, methoxy, and amino; provided that at least one of R 2 and R 3 is hydrogen; R is selected from the group consisting of hydrogen, fluorine, methoxy, cyano, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is selected from the group consisting of CH and C—CH 3 wherein dotted line () represents a bond; R 6 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl, wherein C 1-3 alkyl is optionally substituted with hydroxyl or amino; X 4 is selected from the group consisting of CH 2 and O; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; n 2 is 0 to 2; Y 2 and Y 3 are independently selected from —N and CR 7 ; R 7 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; Z 1 is selected from the group consisting of O, S, and CH 2 ; and R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and fluorine.

4. A compound as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, wherein R 1 is selected from the group consisting of CH 3 , CH 2 CH 3 , CH(CH 3) 2 , cyclopropyl, cyclobutyl, CH 2 CF 3 , CH 2 CHFCH 3 , CH 2 CF 2 CH 3 , CH 2 CH(OH)CH 3 , CH 2 CH 2 OH, CH 2 CH 2 OCH 3 , CH 2 CH(OCH 3)CH 3 , CH 2 CH 2 NH 2 , CH 2 CH 2 NHCH 3 , CH 2 CH(NH 2)CH 3 , CH 2 CH 2 N(CH 3) 2 , CH 2 CHFCH 2 NH 2 , CH 2 CF 2 CH 2 NH 2 , CH 2 CH 2 SO 2 CH 3 , [chemical expression included] R 2 and R 3 are independently selected from the group consisting of hydrogen, fluorine, C 1-6 alkyl, OC 1-6 alkyl, hydroxyl, and amino; provided that at least one of R 2 and R 3 is hydrogen; R is selected from the group consisting of hydrogen, fluorine, cyano, OC 1-6 alkyl, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, OC 1-6 haloalkyl, and C 1-6 alkyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, OC 1-6 haloalkyl, and C 1-6 alkyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is selected from the group consisting of CH and C—C 1-6 alkyl wherein dotted line () represents a bond; R 6 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-3 alkyl, and C 1-3 alkyl, wherein C 1-3 alkyl is optionally substituted with hydroxyl or amino; X 4 is selected from the group consisting of CH 2 and O; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; n 2 is 0 to 2; Y 2 and Y 3 are independently selected from N and CR 7 ; R 7 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; Z 1 is selected from the group consisting of O, S, and CH 2 ; and R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and fluorine.

5. A compound as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms and pharmaceutically active derivatives thereof, wherein R 1 is independently selected from the group consisting of CH 3 , CH 2 CH 3 , CH(CH 3) 2 , cyclopropyl, cyclobutyl, CH 2 CF 3 , CH 2 CHFCH 3 , CH 2 CF 2 CH 3 , CH 2 CH(OH)CH 3 , CH 2 CH 2 OH, CH 2 CH 2 OCH 3 , CH 2 CH(OCH 3)CH 3 , CH 2 CH 2 NH 2 , CH 2 CH 2 NHCH 3 , CH 2 CH(NH 2)CH 3 , CH 2 CH 2 N(CH 3) 2 , CH 2 CHFCH 2 NH 2 , CH 2 CH 2 SO 2 CH 3 , [chemical expression included] R 2 and R 3 are is independently selected from the group consisting of hydrogen, hydroxyl, methoxy, fluorine, and amino; provided that at least one of R 2 and R 3 is hydrogen; R is selected from the group consisting of hydrogen, fluorine, methoxy, cyano, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, OC 1-6 haloalkyl, and C 1-6 alkyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, OC 1-6 haloalkyl, and C 1-6 alkyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is selected from the group consisting of CH and C—CH 3 wherein dotted line () represents a bond; R 6 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with hydroxyl or amino; X 4 is selected from the group consisting of CH 2 and O; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; n 2 is 0 to 2; Y 2 and Y 3 are independently selected from —N and CR 7 ; R 7 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, OC 1-6 haloalkyl, and C 1-6 alkyl; Z 1 is selected from the group consisting of 0, S, and CH 2 ; and R 8 is selected from the group consisting of hydrogen, methyl, and fluorine.

6. A compound as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, wherein R 1 is selected from the group consisting of CH 3 , CH 2 CH 3 , CH(CH 3) 2 , cyclopropyl, cyclobutyl, CH 2 CF 3 , CH 2 CHFCH 3 , CH 2 CF 2 CH 3 , CH 2 CH(OH)CH 3 , CH 2 CH 2 OH, CH 2 CH 2 OCH 3 , CH 2 CH(OCH 3)CH 3 , CH 2 CH 2 NH 2 , CH 2 CH 2 NHCH 3 , CH 2 CH(NH 2)CH 3 , CH 2 CH 2 N(CH 3) 2 , CH 2 CHFCH 2 NH 2 , CH 2 CF 2 CH 2 NH 2 , CH 2 CH 2 SO 2 CH 3 , [chemical expression included] R 2 and R 3 are independently selected from the group consisting of hydrogen, hydroxyl, methyl, methoxy, and amino; provided that at least one of R 2 and R 3 is hydrogen; R is selected from the group consisting of hydrogen, F, CN, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is selected from the group consisting of CH and C—CH 3 wherein dotted line () represents a bond; R 6 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl, wherein C 1-3 alkyl is optionally substituted with hydroxyl or amino; X 4 is selected from the group consisting of CH 2 and O; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; n 2 is 0 to 2; Y 2 and Y 3 are independently selected from —N and CR 7 ; R 7 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; Z 1 is selected from the group consisting of O, S, and CH 2 ; and R 8 is selected from the group consisting of hydrogen, methyl, and fluorine.

7. A compound as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, wherein R 1 is selected from the group consisting of CH 3 , CH 2 CH 3 , CH(CH 3) 2 , cyclopropyl, cyclobutyl, CH 2 CF 3 , CH 2 CHFCH 3 , CH 2 CF 2 CH 3 , CH 2 CH(OH)CH 3 , CH 2 CH 2 OH, CH 2 CH 2 OCH 3 , CH 2 CH(OCH 3)CH 3 , CH 2 CH 2 NH 2 , CH 2 CH 2 NHCH 3 , CH 2 CH(NH 2)CH 3 , CH 2 CH 2 N(CH 3) 2 , CH 2 CHFCH 2 NH 2 , CH 2 CF 2 CH 2 NH 2 , CH 2 CH 2 SO 2 CH 3 , [chemical expression included] R 2 and R 3 are independently selected from the group consisting of hydrogen, methoxy, fluorine, and hydroxyl; provided that at least one of R 2 and R 3 is hydrogen; R is selected from the group consisting of hydrogen, fluorine, methoxy, cyano, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is selected from the group consisting of CH and C—CH 3 wherein dotted line () represents a bond; R 6 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl, wherein C 1-3 alkyl is optionally substituted with hydroxyl or amino; X 4 is selected from the group consisting of CH 2 and O; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; n 2 is 0 to 2; Y 2 and Y 3 are independently selected from —N and CR 7 ; R 7 is selected from the group consisting of hydrogen, fluorine, cyano, —OC 1-3 alkyl, and C 1-3 alkyl; Z 1 is selected from the group consisting of O, S, and CH 2 ; and R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and fluorine.

8. A compound as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, wherein R 1 is selected from the group consisting of CH 3 , CH 2 CH 3 , CH(CH 3) 2 , cyclopropyl, cyclobutyl, CH 2 CF 3 , CH 2 CHFCH 3 , CH 2 CF 2 CH 3 , CH 2 CH(OH)CH 3 , CH 2 CH 2 OH, CH 2 CH 2 OCH 3 , CH 2 CH(OCH 3)CH 3 , CH 2 CH 2 NH 2 , CH 2 CH 2 NHCH 3 , CH 2 CH(NH 2)CH 3 , CH 2 CH 2 N(CH 3) 2 , CH 2 CHFCH 2 NH 2 , CH 2 CF 2 CH 2 NH 2 , CH 2 CH 2 SO 2 CH 3 , [chemical expression included] R 2 and R 3 are independently selected from the group consisting of hydrogen, fluorine, methoxy, amino, and hydroxyl; R is selected from the group consisting of hydrogen, fluorine, cyano methoxy, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, fluorine, cyano, methoxy, and methyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, fluorine, cyano, methoxy, and methyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is selected from the group consisting of CH and C—CH 3 wherein dotted line () represents a bond; R 6 is selected from the group consisting of hydrogen, fluorine, cyano, methoxy, methyl, CH 2 OH, and CH 2 NH 2 ; X 4 is selected from the group consisting of CH 2 and 0; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; n 2 is 0 to 2; Y 2 and Y 3 are independently selected from —N and CR 7 ; R 7 is selected from the group consisting of hydrogen, fluorine, cyano, methoxy, and methyl; Z 1 is 0; and R 8 is selected from the group consisting of hydrogen, methyl, and fluorine.

9. The compound of Formula I as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, which is selected from a group consisting of: 6-(5-(((3-(3-fluoro-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridin-4-yl)propyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 1) [chemical expression included] S)-6-(5-(((2-(7-fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 2) [chemical expression included] (R)-6-(5-(((2-(7-fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 3) [chemical expression included] (S)-6-(5-(((2-(6-fluoro-4-methyl-3-oxo-3,4-dihydroquinoxalin-5-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 4) [chemical expression included] (R)-6-(5-(((2-(6-fluoro-4-methyl-3-oxo-3,4-dihydroquinoxalin-5-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 5) [chemical expression included] (S)-6-(5-(((2-(6-fluoro-2,4-dimethyl-3-oxo-3,4-dihydroquinoxalin-5-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 6) [chemical expression included] (R)-6-(5-(((2-(6-fluoro-2,4-dimethyl-3-oxo-3,4-dihydroquinoxalin-5-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 7) [chemical expression included] (S)-6-(5-(((2-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 8) [chemical expression included] (S)-6-(5-(((2-(6-fluoro-4-(2-hydroxyethyl)-3-oxo-3,4-dihydroquinoxalin-5-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 9) [chemical expression included] (S)-6-(5-(((2-(7-fluoro-1-(2-hydroxyethyl)-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 10) [chemical expression included] (S)-6-(5-(((2-(7-fluoro-1-(2-(methylsulfonyl)ethyl)-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 11) [chemical expression included] (S)-6-(5-(((2-(7-fluoro-4-(hydroxymethyl)-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b] [1,4] oxazin-3 (4H)-one (Example 12) [chemical expression included] S)-6-(5-(((2-(4-(aminomethyl)-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 13) [chemical expression included] (R)-6-(5-(((2-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 14) [chemical expression included] (S)-6-(5-(((2-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 15) [chemical expression included] (S)-2-(5-(((2-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-one (Example 16) [chemical expression included] (S)-2-(5-(((2-(6-fluoro-4-methyl-3-oxo-3,4-dihydroquinoxalin-5-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-one (Example 17) [chemical expression included] 6-(((S)-5-((((S)-3-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)-2-hydroxypropyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 18) [chemical expression included] 6-((S)-5-((((R)-3-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)-2-hydroxypropyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Example 19) [chemical expression included] (S)-6-(5-(((2-(7-fluoro-1-(2-hydroxyethyl)-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 20) [chemical expression included] (S)-6-(5-(((2-(7-fluoro-1-(2-methoxyethyl)-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b] [1,4] oxazin-3 (4H)-one (Example 21) [chemical expression included] (S)-6-(5-(((3-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)propyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 22) [chemical expression included] (R)-6-(5-(((3-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)propyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 23) [chemical expression included] (S)-6-(5-(2-(((2-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 24) [chemical expression included] (R)-6-(5-(2-((2-(7-fluoro-1-methyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 25) [chemical expression included] (S)-6-(5-(((2-(1-ethyl-7-fluoro-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 26) [chemical expression included] (S)-6-(5-(2-(((2-(1-ethyl-7-fluoro-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 27) [chemical expression included] (S)-6-(5-(((2-(7-fluoro-1,4-dimethyl-2-oxo-1,2-dihydroquinolin-8-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 28) [chemical expression included] (S)-6-(5-(((2-(3-fluoro-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridin-4-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 29) [chemical expression included] and (S)-6-(5-(((2-(6-fluoro-4-methyl-3-oxo-3,4-dihydroquinoxalin-5-yl)ethyl)amino)methyl)-2-oxooxazolidin-3-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (Example 30) [chemical expression included]

10. A process for preparation of a compound of Formula I as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, said process comprises reacting Formula (A), and Formula (B) [chemical expression included] in presence of at least one reducing agent and an adsorbent to obtain the compounds of Formula I.

11. The process as claimed in claim 10 , wherein R 1 of Formula (A) is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, C 1-6 alkylamino, C 1-6 aminoalkylene, and 4-7 membered carbocyclyl or heterocyclyl ring which may be fully saturated or unsaturated or partially unsaturated optionally having up to three heteroatoms independently selected from O, N, and S, each of which is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, amino, hydroxyl, C 1-6 alkoxy, SO 3 H, SO 2 R 9 , COORS, CONHR 9 , and SO 2 NHR 9 , wherein R 9 is selected from H, C 1-6 alkyl, methylsulfone, C 1-6 alkyl, OC 1-6 alkyl, OC 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7 membered heterocyclyl ring which may be fully saturated or unsaturated or partially unsaturated optionally having up to three heteroatoms independently selected from O, N, or S, C 3-6 cycloalkylamino, C 3-6 aminocycloalkyl, C 1-6 alkylamino, and di (C 1-6 alkyl)amino; R 2 and R 3 are independently selected from the group consisting of hydrogen, C 1-6 alkyl, fluorine, OC 1-6 alkyl, hydroxyl, and amino; R is selected from the group consisting of hydrogen, fluorine, cyano, OC 1-6 alkyl, and hydroxyl; X 1 is selected from the group consisting of N and CR 4 ; R 4 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; X 2 is selected from the group consisting of N and CR 5 ; R 5 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; X 3 is selected from the group consisting of N and CR 6 ; and X 4 is selected from the group consisting of CH and C—C 1-6 alkyl when dotted line () represents a bond, wherein R 6 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with hydroxyl or amino; X 4 is selected from the group consisting of CH 2 and O; and X 3 is CH 2 when dotted line () represents no bond; n 1 is 0 or 1; Y 2 and Y 3 of Formula (B) are independently selected from —N and CR 7 ; R 7 is selected from the group consisting of hydrogen, halogen, cyano, —OC 1-6 alkyl, C 1-6 haloalkyl, —OC 1-6 haloalkyl, and C 1-6 alkyl; Z 1 is selected from the group consisting of O, S, and CH 2 ; n 2 is 0 to 2; and R 8 is selected from the group consisting of hydrogen, C 1-6 alkyl, and fluorine.

12. The process as claimed in claim 10 , wherein the at least one reducing agent is selected from the group consisting of sodium borohydride, sodium cyano borohydride, sodium triacetoxy borohydride, and combinations thereof.

13. The process as claimed in claim 10 , wherein the adsorbent is selected from the group consisting of molecular sieves, silica gel, zeolites, anhydrous sodium sulphate, anhydrous magnesium sulphate, activated charcoal, and combinations thereof.

14. A method for killing or inhibiting the growth of a microorganism in a sample, by administering the compound as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof to the sample, wherein the microorganism is selected from the group consisting of bacteria, virus, fungi, and protozoa.

15. A method for treatment of bacterial infection in a subject comprising: administering to the subject an effective amount of the compound as claimed in claim 1 .

16. The method as claimed in claim 15 , wherein the bacterial infection is caused by a Gram-positive or a Gram-negative pathogen.

17. The method as claimed in claim 15 , wherein the bacterial infection is caused by E. coli, P. aeruginosa, K. pneumonia, A. baumannii, S. aureus, E. faecalis , or E. faecium.

18. A method of treating a disease or condition in a patient comprising administering a compound as claimed in claim 1 , its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof, wherein said disease or condition is caused by a microorganism selected from the group consisting of Gram-positive and Gram-negative pathogens.

19. A pharmaceutical composition comprising a compound of Formula I as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives thereof together with a pharmaceutically acceptable carrier.

20. A pharmaceutical composition comprising a compound of Formula I as claimed in claim 1 , or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms and pharmaceutically active derivatives thereof together with a pharmaceutically acceptable carrier, and in combination with at least one antibiotic.

WO 2008/126024 October 2008
WO 2010/041194 April 2010
WO 2010/055348 May 2010
WO 2013/068948 May 2013

Hubschwerlen et al., 2013, caplus an 2013:237515. cited by examiner

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