ATP SYNTHASE INHIBITORS AND STEROID ALKALOIDS AND USES THEREOF AS ANTIMICROBIAL AGENTS AND AS POTENTIATORS FOR AMINOGLYCOSIDES AGAINST PATHOGENIC BACTERIA

摘要

The present invention provides bacterial ATP synthase inhibitors such as a compound of formula (I): (Formula (I)) (A) in combination with an aminoglycoside antibiotic for preventing or treating a bacterial infection in a subject; or (B) (a) for preventing or treating an infection caused by an electron transport-deficient bacteria in a subject; or (b) for the disinfection, sterilization and/or antisepsis of an object contaminated with an electron transport-deficient bacteria. There are provided compositions and kits using such compounds and inhibitors.;

主权项

1. A method of using a compound of formula (I): wherein: R1 is H; and R2 is —OH or —NR5R6; or R1 is —OH or —NR5R6; and R2 is H;
wherein R5 and R6 are identical or different and are selected from the group consisting of H; substituted or unsubstituted alkyl; substituted or unsubstituted aryl; substituted or unsubstituted aralkyl; substituted or unsubstituted cycloalkyl, and substituted or unsubstituted —(CH2)nNR7R8,
wherein n is 2-10; andR7 and R8 are identical or different and are selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl; substituted or unsubstituted cycloalkyl, and substituted or unsubstituted aralkyl;wherein the substituted alkyl(s), substituted aryl(s), substituted aralkyl(s), substituted cycloalkyl(s), and substituted —(CH2)nNR7R8 comprise(s) one or more identical or different substitutions selected from alkyl, aryl, cycloalkyl and aralkyl; R3 is —C(CH3)(NHR9),
wherein R9 is H, substituted or unsubstituted alkyl, or substituted or unsubstituted —(CH2)mNR11R12, wherein m is 2-10; and
R11 and R12 are identical or different and are selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted aralkylwherein the substituted alkyl(s), substituted aryl(s), substituted aralkyl(s), substituted cycloalkyl(s), and substituted —(CH2)mNR11R12 comprise(s) one or more identical or different substitutions selected from alkyl, aryl, cycloalkyl and aralkyl; and R4 is H,
with the proviso that when R3 is —C(CH3)(NHR9), R4 is H, R1 is OH and R2 is H, R9 is substituted or unsubstituted alkyl;wherein the substituted alkyl comprises one or more identical or different substitutions selected from alkyl, aryl, cycloalkyl and aralkyl; or R3 and R4 form together with the carbon atoms to which they are attached form a spirocyclic structure of formula II: wherein R10 is H, substituted or unsubstituted alkyl, or substituted or unsubstituted —(CH2)pNR13R14,
wherein p is 2-10; andR13 and R14 are identical or different and are selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted aralkyl;wherein substituted alkyl, substituted aryl, substituted aralkyl, substituted cycloalkyl, and substituted —(CH2)pNR13R14 comprises one or more identical or different substitutions selected from alkyl, aryl, cycloalkyl and aralkyl, with the proviso that when R3 and R4 form together a spirocyclic structure of formula II, neither R1 nor R2 is —OH; and with the proviso that when R1 is NH2 and R2 is H; or R1 is H and R2 is NH2, R10 is not H, or a stereoisomer or mixture of stereoisomers or a salt thereof, (A) in combination with an aminoglycoside antibiotic for preventing or treating a bacterial infection in a subject; or (B) (a) for preventing or treating an infection caused by an electron transport-deficient bacteria in a subject; or (b) for the disinfection, sterilization and/or antisepsis of an object contaminated with an electron transport-deficient bacteria.