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US 2003/0199541 A1Published application
Azabicyclic compounds, preparation thereof and use as medicines, in particular as antibacterial agents
AssigneeAventis Pharma S.A.
InventorsMaxime Lampilas, Jozsef Aszodi, David Alan Rowlands, Claude Fromentin
Life of this patent
Estimating the term…
Abstract
The invention relates to new heterocyclic compounds of general formula (I), and their salts with a base or an acid: 1 The invention also relates to a process for the preparation of these compounds as well as their use as medicaments, in particular as anti-bacterial agents.
Claims39
Compound of general formula (I), or one of its salts with a base or an acid:
- 13
- in which:
- R1 represents a hydrogen atom, a COOH, CN, COOR, CONR6,R7, (CH2)n′R5 or
- 14
- radical,
- R is selected from the group consisting of an alkyl radical containing from 1 to 6 carbon atoms, optionally substituted by a pyridyl or carbamoyl radical, a
- —CH2-alkenyl radical containing at the most 3 to 9 carbon atoms, aryl containing from 6 to 10 carbon atoms or aralkyl containing from 7 to 11 carbon atoms, the ring of the aryl or aralkyl radical being optionally substituted by an OH, NH2, NO2, alkyl radical containing from 1 to 6 carbon atoms, an alkoxy radical containing from 1 to 6 carbon atoms or by one or more halogen atoms,
- R6 and R7 being identical or different, are selected from the group consisting of a hydrogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms and an aralkyl radical containing from 7 to 11 carbon atoms, optionally substituted by a carbamoyl, ureido or dimethylamino radical, and an alkyl radical containing from 1 to 6 carbon atoms substituted by a pyridyl radical,
- n′ is equal to 1 or 2,
- R5 is selected from the group consisting of a COOH, CN, OH, NH2, CO—NR6R7, COOR, OR, OCOH, OCOR, OCOOR, OCONHR, OCONH2, NHR, NHCOH, NHCOR, NHSO2R, NH—COOR, NH—CO—NHR ou NHCONH2, R, R6 and R7 being as defined above;
- R2 represents a hydrogen atom or a (CH2)n′1R5 group, n′1 being equal to 0, 1 or 2 and R5 being as defined above;
- R3 represents -a hydrogen atom or an alkyl radical containing from 1 to 6 carbon atoms;
- A represents a bond between the two carbon carriers of R1 and R2 or a
- 15
- group, R4 representing a hydrogen atom or a (CH2)n′1R5 group, n′1 and R5 being as defined above, the dotted line representing an optional bond with one or other of the carbon carriers of the substituents R1 and R2;
- n is equal to 1 or 2;
- X represents a divalent —C(O)—B— group attached to the nitrogen atom by the carbon atom,
- B represents a divalent —O—(CH2)n″— group attached to the carbonyl by the oxygen atom, an —NR8—(CH2)n″— or —NR8—O— group attached to the carbonyl by the nitrogen atom, n″ is equal to 0 or 1 and R8 is selected from the group consisting of a hydrogen atom, an OH, R, OR, Y, OY, Y1, OY1, Y2, OY2, Y3, OCH2CH2SOmR, OSiRaRbRc and SiRaRbRc radical, Ra, Rb and Rc individually representing a linear or branched alkyl radical containing from 1 to 6 carbon atoms or an aryl radical containing from 6 to 10 carbon atoms, R being as defined above and m being equal to 0, 1 or 2;
- Y is selected from the group consisting of the COH, COR, COOR, CONH2, CONHR, CONHOH, CONHSO2R, CH2COOH, CH2COOR, CH2CONHOH, CH2CONHCN, CH2tetrazole, protected CH2tetrazole, CH2SO3H, CH2SO2R, CH2PO(OR)2, CH2PO(OR) (OH), CH2PO(R)(OH) and CH2PO(OH)2 radicals,
- Y1 is selected from the group consisting of the SO2R, SO2NHCOH, SO2NHCOR, SO2NHCOOR, SO2NHCONHR, SO2NHCONH2 and SO3H radicals,
- Y2 is selected from the group consisting of the PO(OH)2, PO(OR)2, PO(OH) (OR) and PO(OH) (R) radicals,
- Y3 is selected from the group consisting of the tetrazole radicals, tetrazole substituted by the R radical,squarate, NH or NR tetrazole, NH or NR tetrazole substituted by the R radical, NHSO2R and NRSO2R, R being as defined above;
- it being understood that when n is equal to 1 and A represents a
- 16
- group in which R4 is a hydrogen atom and
- either X represents the —C(O)—O—(CH2)n″ group in which n″ is 0 or 1,
- or X represents the —CO—NR8—(CH2)n″ group in which n″ is 1 and R8 is the isopropyl group,
- or X represents the —CO—NR8—(CH2)n″ group in which n″ is 0 and R8 is hydrogen or phenyl,
- so all three of R1, R2 and R3 cannot represent a hydrogen atom at the same time.
26 more elements
A compound selected from the group consisting of:
- trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and its base salts,
- trans-7-oxo-N-(phenylmethyl)-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and its base salts,
- trans-7-oxo-N-(4-pyridinyl methyl)-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and its base salts,
- trans-7-oxo-N-(3-pyridinyl methyl)-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and its base salts,
- trans-7-oxo-N-(2-amino 2-oxo ethyl)-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and its base salts, and
- phenylmethyl trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxylate.
3 more elements
Compound of general formula (I), or one of its salts with a base or an acid:
- 18
- in which:.
- R, represents a hydrogen atom, a COOH, CN, COOR, CONR6,R7 (CH2)n′R5 or
- 19
- radical,
- R is selected from the group consisting of an alkyl radical containing from 1 to 6 carbon atoms, optionally substituted by a pyridyl or carbamoyl radical, a
- —CH2-alkenyl radical containing at the most 3 to 9 carbon atoms, aryl containing from 6 to 10 carbon atoms or aralkyl containing from 7 to 11 carbon atoms, the ring of the aryl or aralkyl radical being optionally substituted by an OH, NH2, NO2, alkyl radical containing from 1 to 6 carbon atoms, an alkoxy radical containing from 1 to 6 carbon atoms or by one or more halogen atoms,
- R6 and R7 being identical or different, are selected from the group consisting of a hydrogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms and an aralkyl radical containing from 7 to 11 carbon atoms, optionally substituted by a carbamoyl, ureido or dimethylamino radical, and an alkyl radical containing from 1 to 6 carbon atoms substituted by a pyridyl radical,
- n′ is equal to 1 or 2,
- R5 is selected from the group consisting of a COOH, CN, OH, NH2, CO—NR6R7, COOR, OR, OCOH, OCOR, OCOOR, OCONHR, OCONH2, NHR, NHCOH, NHCOR, NHSO2R, NH—COOR, NH—CO—NHR ou NHCONH2, R, R6 and R7 being as defined above;
- R2 represents a hydrogen atom or a (CH2)n′1R5 group, n′1 being equal to 0, 1 or 2 and R5 being as defined above;
- R3 represents a hydrogen atom or an alkyl radical containing from 1 to 6 carbon atoms;
- A represents a
- 20
- group, R4 representing a hydrogen atom, or a (CH2)n′1R5 group, n′1 and R5 being as defined above, the dotted line representing an optional bond with one or other of the carbon carriers of the substituents R1 and R2;
- n is equal to 1;
- X represents a divalent —C(O)—B— group attached to the nitrogen atom by the carbon atom,
- B represents an —NR8—(CH2)n″— attached to the carbonyl by the nitrogen atom, n″ is equal to 0 or 1 and R8 is selected from the group consisting of a hydrogen atom, an OH, R, OR, Y, OY, Y1, OY1, Y2, OY2, Y3, OCH2CH2SOmR, OSiRaRbRc and SiRaRbRc radical, Ra, Rb and Rc individually representing a linear or , branched alkyl radical containing from 1 to 6 carbon atoms or an aryl radical containing from 6 to 10 carbon atoms, R being as defined above and m being equal to 0, 1 or 2;
- Y is selected from the group consisting of the COH, COR, COOR, CONH2, CONHR, CONHOH, CONHSO2R, CH2COOH, CH2COOR, CH2CONHOH, CH2CONHCN, CH2tetrazole, protected CH2tetrazole, CH2SO3H, CH2SO2R, CH2PO(OR)2, CH2PO(OR) (OH), CH2PO(R) (OH) and CH2PO(OH)2 radicals,
- Y1 is selected from the group consisting of the SO2R, SO2NHCOH, SO2NHCOR, SO2NHCOOR, SO2NHCONHR, SO2NHCONH2 and SO3H radicals,
- Y2 is selected from the group consisting of the PO(OH)2, PO(OR)2, PO(OH) (OR) and PO(OH) (R) radicals,
- Y3 is selected from the group consisting of the tetrazole radicals, tetrazole substituted by the R radical, squarate, NH or NR tetrazole, NH or NR tetrazole substituted by the R radical, NHSO2R and NRSO2R, R being as defined above;
- it being understood that when n is equal to 1 and A represents a
- 21
- group in which R4 is a hydrogen atom and
- either X represents the —C(O)—O—(CH2)n″ group in which n″ is 0 or 1,
- or X represents the —CO—NR8—(CH2)n″ group in which n″ is 1 and R8 is the isopropyl group,
- or X represents the —CO—NR8—(CH2)n″ group in which n″ is 0 and R8 is hydrogen or phenyl,
- so all three of R1, R2 and R3 cannot represent a hydrogen atom at the same time.
26 more elements
Compound of general formula (I), or one of its salts with a base or an acid:
- 22
- in which:
- R1 represents CONR6R7;
- R6 and R7 being identical or different, are selected from the group consisting of a hydrogen atom, an alkyl radical containing from 1 to 6 carbon atoms, an aryl radical containing from 6 to 10 carbon atoms and an aralkyl radical containing from 7 to 11 carbon atoms, optionally substituted by a carbamoyl, ureido or dimethylamino radical, and an alkyl radical containing from 1 to 6 carbon atoms substituted by a pyridyl radical,
- R2 represents a hydrogen atom;
- R3 represents a hydrogen atom;
- A represents a
- 23
- group,
- R4 representing a hydrogen atom, or a (CH2)n′1R5 group, n′1 is equal to 1 or 2 and R5 is selected from the group consisting of a COOH, CN, OH, NH2, CO—NR6R7, COOR, OR, OCOH, OCOR, OCOOR, OCONHR, OCONH2, NHR, NHCOH, NHCOR, NHSO2R, NH—COOR, NH—CO—NHR ou NHCONH2;
- R is selected from the group consisting of an alkyl radical containing from 1 to 6 carbon atoms, optionally substituted by a pyridyl or carbamoyl radical, a —CH2-alkenyl radical containing at the most 3 to 9 carbon atoms, aryl containing from 6 to 10 carbon atoms or aralkyl containing from 7 to 11 carbon atoms, the ring of the aryl or aralkyl radical being optionally substituted by an OH, NH2, NO2, alkyl radical containing from 1 to 6 carbon atoms, an alkoxy radical containing from 1 to 6 carbon atoms or by one or more halogen atoms;
- R6 and R7 being as defined above, the dotted line representing an optional bond with one or other of the carbon carriers of the substituents R1 and R2;
- n is equal to 1;
- X represents a divalent —C(O)—B— group attached to the nitrogen atom by the carbon atom,
- B represents an —NR8—(CH2)n″— attached to the carbonyl by the nitrogen atom, n″ is equal to 0 or 1 and R8 is selected from the group consisting of a hydrogen atom, an OH, R, OR, Y, OY, Y1, OY1, Y2, OY2, Y3, OCH2CH2SOmR, OSiRaRbRc and SiRaRbRc radical, Ra, Rb and Rc individually representing a linear or branched alkyl radical containing from 1 to 6 carbon atoms or an aryl radical containing from 6 to 10 carbon atoms, R being as defined above and m being equal to 0, 1 or 2;
- Y is selected from the group consisting of the COH, COR, COOR, CONH2, CONHR, CONHOH, CONHSO2R, CH2COOH, CH2COOR, CH2CONHOH, CH2CONHCN, CH2tetrazole, protected CH2tetrazole, CH2SO3H, CH2SO2R, CH2PO(OR)2, CH2PO(OR) (OH), CH2PO(R) (OH) and CH2PO(OH)2 radicals,
- Y1 is selected from the group consisting of the SO2R, SO2NHCOH, SO2NHCOR, SO2NHCOOR, SO2NHCONHR, SO2NHCONH2 and SO3H radicals,
- Y2 is selected from the group consisting of the PO(OH)2, PO(OR)2, PO(OH) (OR) and PO(OH) (R) radicals,
- Y3 is selected from the group consisting of the tetrazole radicals, tetrazole substituted by the R radical, squarate, NH or NR tetrazole, NH or NR tetrazole substituted by the R radical, NHSO2R and NRSO2R, R being as defined above;
16 more elements
Dependencies are inferred from the claim text.