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US 11,274,106 B2Granted
Topoisomerase inhibitors with antibacterial and anticancer activity
AssigneeThe Board of Trustees of the University of Illinois
InventorsPaul J. Hergenrother, Andrew P. Riley
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Abstract
Herein is described the conversion of deoxynybomycin (DNM), a natural product and DNA gyrase inhibitor with minimal cytotoxicity, into a compound (Formula I) that has anticancer activity. Detailed in vitro and cell culture experiments demonstrate that these compounds inhibit Top2 and also act upon topoisomerase I. Similar approaches are applicable to other classes of gyrase inhibitors and other antibacterial targets for discovery of new anticancer drugs.
Claims13
A compound of Formula I:
- or a salt or solvate thereof;
- wherein
- G is a direct bond or CH2;
- X is C═O;
- R1 is H, —(C1-C6)alkyl, —ORA, —SRA, —S(═O)2N(RA)2, —N(RA)2, —(C1-C5)alkyl-ORA, —(C1-C5)alkyl-SRA, —(C1-C5)alkyl-S(═O)2N(RA)2, —(C1-C5)—N(RA)2, or —(C1-C5)alkyl-C(═O)RB;
- R2 is H, —(C1-C6)alkyl, or —(C3-C6)cycloalkyl;
- R3 and R4 are each independently H, —(C1-C6)alkyl, or R3 and R4 taken together form a cycloalkyl or an aryl;
- R5 is H;
- R6 is H or —(C1-C6)alkyl;
- RA is H, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, or —C(═O)RB;
- and
- RB is H, —(C1-C6)alkyl, —OH, or —NH2;
- wherein each —(C1-C6)alkyl, —(C3-C6)cycloalkyl and aryl is optionally substituted with one or more substituents and optionally both RA in the moiety N(RA)2 taken together form a 5- or 6-membered heterocycle;
- and
- the compound of Formula I is not the compound:
12 more elements
A compound of Formula II:
- or a salt or solvate thereof,
- wherein
- R1 is H, —(C1-C6)alkyl, —ORA, —SRA, —S(═O)2N(RA)2, —N(RA)2, —(C1-C5)alkyl-ORA, —(C1-C5)alkyl-SRA, —(C1-C5)alkyl-S(═O)2N(RA)2, —(C1-C5)—N(RA)2, or —(C1-C5)alkyl-C(═O)RB;
- R2 is —(C3-C6)cycloalkyl;
- R3 and R4 are each independently H, —(C1-C6)alkyl, or R3 and R4 taken together form a cycloalkyl or an aryl;
- R6 is H, —(C1-C6)alkyl;
- RA is H, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, or —C(═O)RB;
- and
- RB is H, —(C1-C6)alkyl, —OH, or —NH7;
- wherein each —(C1-C6)alkyl, —(C3-C6)cycloalkyl and aryl is optionally substituted with one or more substituents and optionally both RA in the moiety N(RA)2 taken together form a 5- or 6-membered heterocycle.
7 more elements
A compound selected from any one of compounds C1-C20:
Dependencies are inferred from the claim text.