Claims for Patent: 8,853,197

Summary for Patent: 8,853,197

Title:	Nitrogen containing compounds
Abstract:	Compounds of Formula (I), their preparation and use in preventing or treating bacterial infection is disclosed.
Inventor(s):	Mahesh Vithalbhai Patel, Prasad Keshav Deshpande, Satish Bhawasar, Sachin Bhagwat, Mohammad Alam Jafri, Amit MISHRA, Laxmikant Pavase, Sunil Gupta, Rajesh Kale, Sanjeev Joshi
Assignee:	Wockhardt Ltd
Application Number:	US14/294,364
Patent Claims:	1. A compound of Formula (I) or a stereoisomer or a pharmaceutically acceptable salt thereof; wherein: R1 is: (a) hydrogen, (b) (CO)n—R3, or (c) COOR4. n is 0, 1 or 2; R2 is: (a) SO3M, (b) SO2NH2, (c) PO3M, (d) CH2COOM, (e) CF2COOM, (f) CHFCOOM, or (g) CF3; M is hydrogen or a cation; R3 is: (a) hydrogen, (b) C1-C6 alkyl optionally substituted with one or more substituents independently selected from halogen, OR5, CN, COOR5, CONR6R7, NR6R7, NR5COR8, NR5CONR6R7, heterocyclyl, heteroaryl, cycloalkyl or aryl, (c) CN, (d) NR6R7, (e) CONR6R7, (f) NHCONR6R7, (g) aryl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR6R7, halogen, CN, CONR6R7, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR6R7, (h) heterocyclyl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR6R7, halogen, CN, CONR6R7, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR6R7, (i) heteroaryl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR6R7, halogen, CN, CONR6R7, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR6R7, (j) cycloalkyl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR6R7, halogen, CN, CONR6R7, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR6R7, (k) cycloalkyl substituted with C1-C6 alkyl wherein C1-C6 alkyl is further substituted with one or more substituents independently selected from OR5, NR6R7, halogen, CN, or CONR6R7, or (l) ORB; R4 is: (a) hydrogen, (b) C1-C6 alkyl optionally substituted with one or more substituents independently selected from halogen, OR5, CN, COOR5, CONR6R7, NR6R7, NR5COR8, heterocyclyl, heteroaryl, cycloalkyl or aryl, (c) aryl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR6R7, halogen, CN, CONR6R7, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR6R7, (d) heterocyclyl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR6R7, halogen, CN, CONR6R7, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR6R7, (e) heteroaryl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR6R7, halogen, CN, CONR6R7, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR6R7, or (f) cycloalkyl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR6R7, halogen, CN, CONR6R7, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR6R7; R5 and R8 are each independently: (a) hydrogen, or (b) C1-C6 alkyl optionally substituted with one or more substituents independently selected from halogen, CN, CONR6R7, NR6R7, heterocyclyl, heteroaryl, cycloalkyl or aryl; R6 and R7 are each independently: (a) hydrogen, (b) C1-C6 alkyl optionally substituted with one or more substituents independently selected from halogen, OR5, CN, COOR5, CONR5R8, NR5R8, NR5COR8, heterocyclyl, heteroaryl, cycloalkyl or aryl, (c) aryl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR5R8, halogen, CN, CONR5R8, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR5R8, (d) heterocyclyl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR5R8, halogen, CN, CONR5R8, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR5R8, (e) heteroaryl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR5R8, halogen, CN, CONR5R8, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR5R8, (f) cycloalkyl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, OR5, NR5R8, halogen, CN, CONR5R8, SO2-alkyl, SO2-aryl, OSO2-alkyl, OSO2-aryl, or NHCONR5R8, or (g) R6 and R7 are joined together to form a four to seven member ring. 2. A compound according to claim 1, selected from: trans-sulfuric acid mono-[2-(N′-[(S)-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((R)-piperidin-3-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-hydrazinocarbonyl-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(amino-acetyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(3-amino-propioyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(4-amino-butanoyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-((2S)-2-amino-3-hydroxy-propioyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[(2S,4S)-4-fluoro-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[(2S,4R)-4-methoxy-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(piperidin-4-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((RS)-piperidin-3-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((S)-piperidin-3-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((RS)-piperidin-2-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((S)-piperidin-2-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((R)-piperidin-2-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(piperazin-4-yl-acetyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((RS)-1-amino-1-phenyl-acetyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(3-amino-2,2-dimethyl-propioyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(1-aminomethyl-cyclopropan-1-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(5-amino-pentanoyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[(R)-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(2-amino-thiazol-4-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; or a stereoisomer or a pharmaceutically acceptable salt thereof. 3. A compound according to claim 1, selected from: trans-sulfuric acid mono-[2-(N′-[(R)-pyrrolidin-3-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-{7-oxo-2-[N′—((R)-piperidin-3-carbonyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-oct-6-yloxy}-acetic acid; trans-difluoro-{7-oxo-2-[N′—((R)-piperidin-3-carbonyl)-hydrazinocarbonyl]-1,6-diaza-bicyclo[3.2.1]-oct-6-yloxy}-acetic acid; trans-sulfuric acid mono-[2-(N′—((RS)-3-amino-butanoyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-(2-amino-4-carboxamido-butanoyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-((2S)-2,6-diamino-hexanoyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-((2-aminoethoxy)-acetyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[azetidin-3-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[pyrrolidin-1-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[((S)-3-pyrrolidin-2-yl)-propionyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[(RS)-pyrrolidin-3-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[(S)-pyrrolidin-3-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[(2S,4R)-4-hydroxy-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[(2S,4S)-4-amino-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′-[(RS)-3-piperidin-2-yl-propionyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((RS)-piperazin-2-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((S)-morpholin-3-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; trans-sulfuric acid mono-[2-(N′—((RS)-1-amino-1-pyridin-2-yl-acetyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; or a stereoisomer or a pharmaceutically acceptable salt thereof. 4. A compound according to claim 1, selected from: Sodium salt of trans-sulfuric acid mono-[2-(N′-(cyano-acetyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; Sodium salt of trans-N′-(7-oxo-6-sulfooxy-1,6-diaza-bicyclo[3.2.1]octane-2-carboxylic acid)-hydrazinecarboxylic acid tert-butyl ester; Sodium salt of trans-sulfuric acid mono-[2-(N′-(morpholin-4-yl-acetyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; Sodium salt of trans-sulfuric acid mono-[2-(N′-(6-carboxamido-pyridin-2-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; Sodium salt of trans-sulfuric acid mono-[2-(N′-(morpholin-4-oxo-carbonyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; Sodium salt of trans-sulfuric acid mono-[2-(N′-[(S)-1-carbamoyl-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; Sodium salt of trans-sulfuric acid mono-[2-(N′-[(2S,4S)-1-carbamoyl-4-fluoro-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; Sodium salt of trans-sulfuric acid mono-[2-(N′-[(S)-1-methanesulfonyl-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; Sodium salt of trans-sulfuric acid mono-[2-(N′-(cyano-dimethyl-acetyl)-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; Sodium salt of trans-sulfuric acid mono-[2-(N′-[(S)-5-oxo-pyrrolidin-2-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester; or a stereoisomer thereof. 5. A compound which is trans-sulfuric acid mono-[2-(N′-[(R)-piperidin-3-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester or a stereoisomer or a pharmaceutically acceptable salt thereof. 6. A compound which is trans-sulfuric acid mono-[2-(N′-[(R)-pyrrolidin-3-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester or a stereoisomer or a pharmaceutically acceptable salt thereof. 7. A pharmaceutical composition comprising a compound according to claim 1. 8. A pharmaceutical composition comprising a compound according to claim 2. 9. A pharmaceutical composition comprising a compound according to claim 3. 10. A pharmaceutical composition comprising a compound according to claim 4. 11. A pharmaceutical composition comprising a compound according to claim 5. 12. A pharmaceutical composition comprising a compound according to claim 6. 13. A pharmaceutical composition according to claim 7, comprising trans-sulfuric acid mono-[2-(N′-[(R)-piperidin-3-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester or a stereoisomer or a pharmaceutically acceptable salt thereof. 14. A pharmaceutical composition according to claim 7, comprising trans-sulfuric acid mono-[2-(N′-[(R)-pyrrolidin-3-carbonyl]-hydrazinocarbonyl)-7-oxo-1,6-diaza-bicyclo[3.2.1]oct-6-yl]ester or a stereoisomer or a pharmaceutically acceptable salt thereof.