Promysalin analogues and methods of use thereof
AssigneeTemple University of the Commonwealth System of Higher Education
InventorWilliam M. Wuest
Life of this patent
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Abstract
The present invention includes novel analogs of promysalin useful in preventing or treating a microbial infection. The present invention also includes methods preventing or treating a microbial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of the invention.
Claims20
A compound of formula I, or a salt thereof:
- wherein in formula I:
- R1, R2, R3, R4, and R5 are each independently selected from the group consisting of H, —C1-C6 alkyl, —C1-C6 fluoroalkyl, —C1-C6 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, F, Cl, Br, I, —CN, —NO2, —OH, —OR7, —SR7, —S(═O)R7, —S(═O)2R7, —NHS(═O)2R7, —C(═O)R7, —OC(═O)R7, —CO2R7, —OCO2R7, —CH(R7)2, —N(R7)2, —C(═O)N(R7)2, —OC(═O)N(R7)2, —NHC(═O)NH(R7), —NHC(═O)R7, —NHC(═O)OR7, —C(OH)(R7)2, and —C(NH2)(R7)2, wherein the alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, and C1-C6 heteroalkyl group is optionally substituted;
- R6 is selected from the group consisting of —C1-C6 alkyl, —C1-C6 fluoroalkyl, —C1-C6 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, F, Cl, Br, I, —CN, —NO2, —OH, —OR7, —SR7, —S(═O)R7, —S(═O)2R7, —NHS(═O)2R7, —C(═O)R7, —OC(═O)R7, —CO2R7, —OCO2R7, —CH(R7)2, —N(R7)2, —C(═O)N(R7)2, —OC(═O)N(R7)2, —NHC(═O)NH(R7), —NHC(═O)R7, —NHC(═O)OR7, —C(OH)(R7)2, and —C(NH2)(R7)2, wherein the alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, and C1-C6 heteroalkyl group is optionally substituted;
- each occurrence of R7 is independently selected from the group consisting of H and —C1-C6 alkyl, wherein the alkyl group is optionally substituted;
- the bond between carbons 1 and 2 and the bond between carbons 3 and 4 each independently represents a single or double bond;
- X is O or NR7;
- Y is selected from the group consisting of H, OR7, halogen, and —NHR7;
- n is 1 or 2;
- and
- m is an integer from 0 to 8;
- with the proviso that the compound of formula I is not:
A compound selected from the group consisting of (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-(2-hydroxybenzoyl)piperidine-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S,4R)-4-hydroxy-1-(2-hydroxybenzoyl)pyrrolidine-2-carboxylate, (7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl (S)-4-fluoro-1-(2-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl (S)-1-(2-hydroxybenzoyl)-4-methyl-2,3-dihydro-1H-pyrrole-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-(2-methoxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl (S)-1-(3-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-(4-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-benzoyl-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl (S)-1-(2-hydroxy-6-methoxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-(3,4,5-trimethoxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl (S)-1-(2-nitrobenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-methoxy-14-oxotetradecan-7-yl (S)-1-(2-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (S)—N-((7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl)-1-(2-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxamide, and (7R,13R,E)-14-amino-13-hydroxy-14-oxotetradec-9-en-7-yl (S)-1-(2-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, or a salt thereof.
A method of preventing or treating a Psuedomonas infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a therapeutic composition comprising:
- (a) at least one compound of formula I, or a salt thereof:
- wherein in formula I:
- R1, R2, R3, R4, and R5 are each independently selected from the group consisting of H, —C1-C6 alkyl, —C1-C6 fluoroalkyl, —C1-C6 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, F, Cl, Br, I, —CN, —NO2, —OH, —OR7, —SR7, —S(═O)R7, —S(═O)2R7, —NHS(═O)2R7, —C(═O)R7, —OC(═O)R7, —CO2R7, —OCO2R7, —CH(R7)2, —N(R7)2, —C(═O)N(R7)2, —OC(═O)N(R7)2, —NHC(═O)NH(R7), —NHC(═O)R7, —NHC(═O)OR7, —C(OH)(R7)2, and —C(NH2)(R7)2, wherein the alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, and C1-C6 heteroalkyl group is optionally substituted;
- R6 is selected from the group consisting of —C1-C6 alkyl, —C1-C6 fluoroalkyl, —C1-C6 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, F, Cl, Br, I, —CN, —NO2, —OH, —OR7, —S(═O)R7, —S(═O)2R7, —NHS(═O)2R7, —C(═O)R7, —OC(═O)R7, —CO2R7, —OCO2R7, —CH(R7)2, —N(R7)2, —C(═O)N(R7)2, —OC(═O)N(R7)2, —NHC(═O)NH(R7), —NHC(═O)R7, —NHC(═O)OR7, —C(OH)(R7)2, and —C(NH2)(R7)2, wherein the alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, and C1-C6 heteroalkyl group is optionally substituted;
- each occurrence of R7 is independently selected from the group consisting of H and —C1-C6 alkyl, wherein the alkyl group is optionally substituted;
- the bond between carbons 1 and 2 and the bond between carbons 3 and 4 each independently represents a single or double bond;
- X is O or NR1;
- Y is selected from the group consisting of H, OR7, halogen, and —NHR7;
- n is 1 or 2;
- and
- m is an integer from 0 to 8;
- with the proviso that the compound of formula I is not:
- or
- (b) a compound selected from the group consisting of (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-(2-hydroxybenzoyl)piperidine-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-(2-methoxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl (S)-1-(3-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-(4-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-benzoyl-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl (S)-1-(2-hydroxy-6-methoxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (1R,7R)-1-carbamoyl-1-hydroxytridecan-7-yl (2S)-1-(3,4,5-trimethoxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl (S)-1-(2-nitrobenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (7R,13R)-14-amino-13-methoxy-14-oxotetradecan-7-yl (S)-1-(2-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, (S)—N-((7R,13R)-14-amino-13-hydroxy-14-oxotetradecan-7-yl)-1-(2-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxamide, and (7R,13R,E)-14-amino-13-hydroxy-14-oxotetradec-9-en-7-yl (S)-1-(2-hydroxybenzoyl)-2,3-dihydro-1H-pyrrole-2-carboxylate, or a salt thereof.
Dependencies are inferred from the claim text.