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US 11,034,649 B2Granted
Benzoylglycine derivatives and methods of making and using same
AssigneesDuke University, The University of North Carolina at Chapel Hill
InventorsPei Zhou, Eric J. Toone, Robert A. Nicholas, Ramesh Gopalaswamy, Xiaofei Liang, Frank Navas, III
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Abstract
Disclosed are compounds of formulae: and pharmaceutically acceptable salts thereof, wherein the variables, R1, R2, R3, R4, R5, R6, R7, R11, R12, R13, R14, R15, R16, R17, n, and m are defined herein. These compounds are useful for treating Gram-negative bacteria infections. Also disclosed are methods of making these compounds.
Claims20
A compound, which is:
- or a pharmaceutically acceptable salt thereof.
A compound of the formula:
- or a pharmaceutically acceptable salt thereof, wherein
- m is an integer 0, 1, 2, 3, or 4;
- R11 is —C≡C—R10, C1-C6 alkyl, C1-C6 haloalkyl, —CO(C1-C6 alkyl), —C1-C6 alkyl-CO(C1-C6 alkyl), —C1-C6 alkyl-CO2H, C3-C8 cycloalkyl optionally substituted with R18, (C3-C8 cycloalkyl)C1-C6 alkyl- optionally substituted with R18, or heterocyclyl optionally substituted with R18;
- wherein R10 is C1-C6 alkyl, C1-C6 haloalkyl, —CO(C1-C6 alkyl), —C1-C6 alkyl-CO(C1-C6 alkyl), —C1-C6 alkyl-CO2H, C3-C8 cycloalkyl optionally substituted with R19, (C3-C8 cycloalkyl)C1-C6 alkyl- optionally substituted with R19, or heterocyclyl optionally substituted with R19;
- R12 is selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —SH, —S(C1-C6 alkyl), hydroxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), and amino(C1-C6 alkyl);
- R13 is selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —SH, —S(C1-C6 alkyl), hydroxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), amino(C1-C6 alkyl), —NHCO(C1-C6 alkyl), —NHCONH2, —NHCONH(C1-C6 alkyl), —OCO(C1-C6 alkyl), and —NHCO(C1-C6 alkoxy);
- R14 is C1-C6 haloalkyl;
- R15 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —CONH2, —CON(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CONH—OH, —CONH—OCO(C1-C6 alkyl), —CONH—NH2, —CO2H, and —CO2(C1-C6 alkyl);
- R16 is hydrogen or C1-C6 alkyl;
- each R17 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, and C1-C6 haloalkoxy;
- each R18 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —C1-C6 alkyl-OH, —C1-C6 alkyl-(C1-C6 alkoxy), —C1-C6 alkyl-NH2, —C1-C6 alkyl-NH—C1-C6 alkyl), —C1-C6 alkyl-N(C1-C6 alkyl)2, —C1-C6 alkyl-NH(SO2C1-C6 alkyl), —CONH2, —CON(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —NH(SO2C1-C6 alkyl), —CONH—OH, —CONH—OCO(C1-C6 alkyl), —C(NH)NH—OH, —CONH—NH2, —CO(C1-C6 alkyl), —CO2H, —CO2(C1-C6 alkyl), —C1-C6 alkyl-CONH2, —C1-C6 alkyl-CON(C1-C6 alkyl), —C1-C6 alkyl-CON(C1-C6 alkyl)2, —C1-C6 alkyl-CONH—OH, —C1-C6 alkyl-CO(C1-C6 alkyl), —C1-C6 alkyl-CO2H, and —C1-C6 alkyl-CO2(C1-C6 alkyl);
- or two R18 groups when attached to the same carbon atom form ═O;
- and
- each R19 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —C1-C6 alkyl-OH, —C1-C6 alkyl-(C1-C6 alkoxy), —C1-C6 alkyl-NH2, —C1-C6 alkyl-NH—C1-C6 alkyl), —C1-C6 alkyl-N(C1-C6 alkyl)2, —C1-C6 alkyl-NH(SO2C1-C6 alkyl), —CONH2, —CON(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —NH(SO2C1-C6 alkyl),—CONH—OH, —CONH—OCO(C1-C6 alkyl), —C(NH)NH—OH, —CONH—NH2, —CO(C1-C6 alkyl), —CO2H, —CO2(C1-C6 alkyl), —C1-C6 alkyl-CONH2, —C1-C6 alkyl-CON(C1-C6 alkyl), —C1-C6 alkyl-CON(C1-C6 alkyl)2, —C1-C6 alkyl-CONH—OH, —C1-C6 alkyl-CO(C1-C6 alkyl), —C1-C6 alkyl-CO2H, and —C1-C6 alkyl-CO2(C1-C6 alkyl);
- or two R19 groups when attached to the same carbon atom form ═O.
12 more elements
A compound, which is:
- or pharmaceutically acceptable salts thereof.
A method of treating Gram-negative bacterial infections, the method comprising administering to a subject in need of such treatment an effective amount of one or more compounds of formula:
- or a pharmaceutically acceptable salt thereof, wherein
- Y represents aryl optionally substituted with R8, heteroaryl optionally substituted with R8, or heterocyclyl optionally substituted with R8;
- n is an integer 0, 1, 2, 3, or 4;
- R1 is hydrogen, C1-C6 alkyl optionally substituted with R9, aryl optionally substituted with R9, heteroaryl optionally substituted with R9, or heterocyclyl optionally substituted with R9;
- R2 is selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —SH, —S(C1-C6 alkyl), hydroxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), and amino(C1-C6 alkyl);
- R3 is selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —SH, —S(C1-C6 alkyl), hydroxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), amino(C1-C6 alkyl), —NHCO(C1-C6 alkyl), —NHCONH2, —NHCONH(C1-C6 alkyl), —OCO(C1-C6 alkyl), and —NHCO(C1-C6 alkoxy);
- R4 is C1-C6 haloalkyl;
- R5 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —CONH2, —CON(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CONH—OH, —CONH—OCO(C1-C6 alkyl), —CONH—NH2, —CO2H, and —CO2(C1-C6 alkyl);
- R6 is hydrogen or C1-C6 alkyl;
- each R7 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, and C1-C6 haloalkoxy;
- each R8 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —CONH2, —CON(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CONH—OH, —CONH—OCO(C1-C6 alkyl), —C(NH)NH—OH, —CONH—NH2, —CO2H, and —CO2(C1-C6 alkyl);
- or two R8 groups when attached to the same carbon atom form ═O;
- and
- each R9 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, and C1-C6 haloalkoxy;
- or two R9 groups when attached to the same carbon atom form ═O.
12 more elements
Dependencies are inferred from the claim text.