Inhibitors of β-lactamase
View Patent ↗The intention relates to bacterial antibiotic resistance and, in particular, to compositions and methods for overcoming bacterial antibiotic resistance. The invention provides novel β-lactamase inhibitors, which are structurally unrelated to the natural product and semi-synthetic β-lactamase inhibitors presently available, and which do not require a β-lactam pharmacophore. The invention also provides pharmaceutical compositions and methods for inhibiting bacterial growth.
1. A compound of the following formula:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is optionally substituted phenyl;
L is a covalent bond, —CH 2 O—, —C(O)—, or —C(═N—OCH 3 )—; and
R 5 is -halo or —OR 10 wherein R 10 is phenyl, pyridinyl, or quinolinyl, each optionally substituted,
provided that when L is —CH 2 O—, R 5 is not —F or p-nitrophenyl.
2. The compound according to claim 1 wherein the substituents of the optionally substituted phenyl of R 1 and the optionally substituted phenyl, pyridinyl, and quinolinyl of R 10 are independently selected from —NO 2 , —CO 2 H, and halo.
3. The compound according to claim 1 wherein R 1 is unsubstituted.
4. The compound according to claim 1 wherein R 5 is selected from:
5. The compound according to claim 1 wherein R 1 —L and R 5 are selected from the following combinations:
R 1 —L—
R 5
and
6. A compound of the following formula:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is optionally substituted phenyl;
L is a covalent bond, —CH 2 O—, —C(O)—, or —C(═N—OCH 3 )—; and
R 5 is -halo or —OR 10 wherein R 10 is —H, phenyl, pyridinyl, or quinolinyl, each optionally substituted,
provided that when L is —CH 2 O—, R 5 is not —F or p-nitrophenyl, and when R 1 —L— s benzyloxy, R 5 is not PNP.