Pyrrolidine and thiazole derivatives with metallo-beta-lactamase inhibitory properties
AssigneeSmithKline Beecham Corporation
InventorsJohn Hargreaves Bateson, Desmond John Best
Life of this patent
Estimating the term…
Abstract
A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a β-lactam antibiotic, a therapeutically effective amount of an amino acid derivative or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof.
Claims15
A compound of formula (ID) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof:
- wherein
- R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group;
- R1A is unsubstituted or substituted aryl or heteroaryl;
- R2A is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl;
- R3 and R5 together complete a carbocyclic ring having 4 to 8 ring atoms, which may be saturated, unsaturated or aromatic, optionally fused to a phenyl ring, and optionally substituted by 1-3 halo, phenyl, (C1-6)alkoxy optionally substituted by 1-3 halo, hydroxy(C1-6)alkyl, mercapto(C1-6)alkyl, hydroxy, CO2R7, N(R7)2 or CON(R7)2 where each R7 is independently hydrogen or (C1-6)alkyl, OCONH2, nitro, (C1-6) alkylcarbonyloxy, (C1-6)alkoxycarbonyl(C1-6)alkyl, formyl, or (C1-6) alkylcarbonyl groups;
- and
- R4 is hydrogen, or an in vivo hydrolysable acyl group.
A compound which is:
- N-[2-(R,S)- mercapto-1-(R,S)-cyclopentanoyl]-D-phenylglycine;
- N-[1-(R,S)- mercapto-2-(R,S)-indanecarbonyl]-D-phenylglycine;
- N-[1-(R,S)- mercapto-2-(R,S)-tetralincarbonyl]-D-phenylglycine;
- or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester of any of the foregoing compounds.
A method of treating bacterial infections in humans or animals which comprises administering, in combination with a β-lactam antibiotic, a therapeutically effective amount of a compound of Formula ID or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof to a subject in need thereof:
- wherein
- R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group;
- R1A is unsubstituted or substituted aryl or heteroaryl;
- R2A is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl;
- R3 and R5 together complete a carbocyclic ring having 4 to 8 ring atoms, which may be saturated, unsaturated or aromatic, optionally fused to a phenyl ring, and optionally substituted by 1-3 halo, phenyl, (C1-6)alkoxy optionally substituted by 1-3 halo, hydroxy(C1-6)alkyl, mercapto(C1-6)alkyl, hydroxy, CO2R7, N(R7)2 or CON(R7)2 where each R7 is independently hydrogen or (C1-6) alkyl, OCONH2, nitro, (C1-6) alkylcarbonyloxy, (C1-6)alkoxycarbonyl(C1-6) alkyl, formyl, or (C1-6) alkylcarbonyl groups;
- and
- R4 is hydrogen, or an in vivo hydrolysable acyl group.
Dependencies are inferred from the claim text.