Indoline sulfonamide inhibitors of dape and ndm-1 and use of the same
AssigneesLoyola University of Chicago, Board of Regents, The University of Texas System
InventorsDaniel Paul Becker, Tahirah K. Heath, Cory Reidl, Walter Fast
Life of this patent
Estimating the term…
Abstract
Indoline sulfonamide compounds that can inhibit DapE and/or bacterial metallo-β-lactamases (MBLs), such as NDM-1, are disclosed. Also disclosed are methods of treating an individual suffering from a bacterial infection using the indoline sulfonamide compounds disclosed herein.
Claims69
A method of inhibiting DapE, bacterial metallo-β-lactamase (MBL), or both in a cell comprising contacting the cell with a compound of Formula (III):
- wherein
- the dashed lines indicate that the sulfonamide moiety can be attached to either the 6-position or the 7-position of the indoline sulfonamide compound;
- R1 is H, C1-8alkyl, OC1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-6alkyleneR6, (C═O)C1-6alkyl, aryl, or heteroaryl;
- R2 is C1-6 alkyl or O—C1-4alkyleneR6;
- R5 is H, C1-8alkyl, C1-6alkyleneR6, or C3-8cycloalkyl,
- or R1 and R5 are taken together with the nitrogen to which they are attached to form a 5- to 7-membered ring;
- R6 is H aryl, (C═O)OH, (C═O)OC1-3alkyl, OC1-3alkyl, SC1-3alkyl, O(C═O)C1-3alkyl;
- and
- X is I, Br, Cl, F, or H.
A method of treating a disease or condition wherein inhibition of DapE and/or MBL provides a benefit, comprising administering a therapeutically effective amount of a compound of Formula (III), or a pharmaceutically acceptable salt thereof:
- wherein
- the dashed lines indicate that the sulfonamide moiety can be attached to either the 6-position or the 7-position of the indoline sulfonamide compound;
- R1 is H, C1-8alkyl, OC1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C1-6alkyleneR6, (C═O)C1-6alkyl, aryl, or heteroaryl;
- R2 is C1-6 alkyl or O—C1-4alkyleneR6;
- R5 is H, C1-8alkyl, C1-6alkyleneR6, or C3-8cycloalkyl,
- or R1 and R5 are taken together with the nitrogen to which they are attached to form a 5- to 7-membered ring;
- R6 is H aryl, (C═O)OH, (C═O)OC1-3alkyl, OC1-3alkyl, SC1-3alkyl, O(C═O)C1-3alkyl;
- and
- X is I, Br, Cl, F, or H.
A compound having a structure of Formula (IIIA), or a pharmaceutically acceptable salt thereof.
- wherein
- R1 is H, C1-8alkyl, C1-6alkyleneR6, aryl, or heteroaryl;
- R2 is C1-6 alkyl or O—C1-4alkyleneR6;
- R5 is H, C1-8alkyl, C1-6alkyleneR6, or C3-8cycloalkyl,
- or R1 and R5 are taken together with the nitrogen to which they are attached to form a 5- to 7-membered ring;
- R6 is aryl, (C═O)OC1-3alkyl, OC1-3alkyl, O(C═O)C1-3alkyl;
- and
- X is Br or Cl.
A compound selected from the group consisting of
A compound selected from the group consisting of
Dependencies are inferred from the claim text.