Compounds affecting pigment production and methods for treatment of bacterial diseases

Abstract

Provided herein are compounds, derivatives thereof, composition comprising one or more of said compounds and derivatives, and methods for prevention and/or treatment of microbial infections and/or related diseases or conditions. The present compounds and/or derivatives thereof can be represented by Formula (II): The present methods include administering to a subject an effective amount of one or more compounds of Formula (II). In one embodiment, said microbial infections are bacterial infections. More specifically, said bacterial infections are staphylococcal infections.

1 . A compound having formula (II): 
       
         
           
           
               
               
           
         
       
       and derivatives thereof,
 wherein R1 is selected from: 
 
       
         
           
           
               
               
           
         
       
       or
 any four-, five-, six-, seven-, eight-, nine-, ten-, eleven-, or twelve-membered heterocyclyl, cycloalkenyl, or cycloalkyl, 
 wherein R3 and R4 are independently or jointly selected from the group consisting of H; F; Cl; Br; I; OH; CN; (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers thereof; alkynyl; aralkyl; alkaryl; halogenated alkyl; heteroalkyl; aryl; heterocyclyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxyalkyl; aminoalkyl; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; acylamino; hydroxyl; thiol; thioalkyl; alkoxy; alkylthio; alkoxyalkyl; aryloxy; arylalkoxy; acyloxy; nitro; carbamoyl; trifluoromethyl; phenoxy; benzyloxy; phosphonic acid; phosphate ester; sulfonic acid (—SO 3 H); sulfonate ester; sulfonamide; alkaryl; arylalkyl; carbamate; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; alkylthio; heteroalkyl; alkyltriphenylphosphonium; heterocyclyl; ketone (═O); ether (—OR10); and ester (—COOR11 and —OC(═O)R11), 
 or R3 and R4 are optionally bonded together to form a four-, five-, or six-membered heterocyclyl, cycloalkenyl, or cycloalkyl, 
 R5 is selected from the group consisting of H; F; Cl; Br; I; OH; CN; (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers thereof; alkynyl; aralkyl; alkaryl; halogenated alkyl; heteroalkyl; aryl; heterocyclyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxyalkyl; aminoalkyl; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; acylamino; hydroxyl; thiol; thioalkyl; alkoxy; alkylthio; alkoxyalkyl; aryloxy; arylalkoxy; acyloxy; nitro; carbamoyl; trifluoromethyl; phenoxy; benzyloxy; phosphonic acid; phosphate ester; sulfonic acid (—SO 3 H); sulfonate ester; sulfonamide; alkaryl; arylalkyl; carbamate; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; alkylthio; heteroalkyl; alkyltriphenylphosphonium; heterocyclyl; ketone (═O); ether (—OR10); and ester (—COOR11 and —OC(═O)R11), and 
 wherein R10 and R11 are independently or jointly selected from the group consisting of a (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers; and alkynyl, 
 X is selected from N or C, 
 A is single bond or double bond, 
 Q is selected from N or C, 
 M is selected from O or C, and 
 wherein R2 is selected from: 
 
       
         
           
           
               
               
           
         
         wherein R6 and R7 are independently or jointly selected from O or absent; 
         R8 and R9 are independently or jointly selected from the group consisting of H; F; Cl; Br; I; OH; CN; (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers thereof; alkynyl; aralkyl; alkaryl; halogenated alkyl; heteroalkyl; aryl; heterocyclyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxyalkyl; aminoalkyl; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; acylamino; hydroxyl; thiol; thioalkyl; alkoxy; alkylthio; alkoxyalkyl; aryloxy; arylalkoxy; acyloxy; nitro; carbamoyl; trifluoromethyl; phenoxy; benzyloxy; phosphonic acid; phosphate ester; sulfonic acid (—SO 3 H); sulfonate ester; sulfonamide; alkaryl; arylalkyl; carbamate; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; alkylthio; heteroalkyl; alkyltriphenylphosphonium; heterocyclyl; ketone (═O); ether (—OR10); and ester (—COOR11 and —OC(═O)R11), 
         or R8 and R9 are optionally bonded together to form a four-, five-, or six-membered heterocyclyl, cycloalkenyl, or cycloalkyl. and 
         wherein R10 and R11 are independently or jointly selected from the group consisting of a (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers; and alkynyl, and 
         Z is selected from C or S. 
       
     
     
         2 . The compound of  claim 1 , wherein the derivatives comprise: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         3 . A composition comprising the compound according to  claim 1 , the derivatives thereof, and a pharmaceutical carrier salt, ester, expicient, vehicle, prodrug, solvent, and diluent, or any combination thereof. 
     
     
         4 . A composition comprising the compound according to  claim 2 , the derivatives thereof, and a pharmaceutical carrier salt, ester, excipient, vehicle, prodrug, solvent, and diluent, or any combination thereof. 
     
     
         5 . A method of treating and/or preventing microbial infections and/or related diseases or conditions in a subject comprising:
 administering to said subject an effective amount of one or more compounds of formula (II):   
       
         
           
           
               
               
           
         
         wherein R1 is selected from: 
       
       
         
           
           
               
               
           
         
       
       or
 any four-, five-, six-, seven-, eight-, nine-, ten-, eleven-, or twelve-membered heterocyclyl, cycloalkenyl, or cycloalkyl, 
 wherein R3 and R4 are independently or jointly selected from the group consisting of H; F; Cl; Br; I; OH; CN; (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers thereof; alkynyl; aralkyl; alkaryl; halogenated alkyl; heteroalkyl; aryl; heterocyclyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxyalkyl; aminoalkyl; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; acylamino; hydroxyl; thiol; thioalkyl; alkoxy; alkylthio; alkoxyalkyl; aryloxy; arylalkoxy; acyloxy; nitro; carbamoyl; trifluoromethyl; phenoxy; benzyloxy; phosphonic acid; phosphate ester; sulfonic acid (—SO 3 H); sulfonate ester; sulfonamide; alkaryl; arylalkyl; carbamate; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; alkylthio; heteroalkyl; alkyltriphenylphosphonium; heterocyclyl; ketone (═O); ether (—OR10); and ester (—COOR11 and —OC(═O)R11), 
 or R3 and R4 are optionally bonded together to form a four-, five-, or six-membered heterocyclyl, cycloalkenyl, or cycloalkyl, 
 R5 is selected from the group consisting of H; F; Cl; Br; I; OH; CN; (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers thereof; alkynyl; aralkyl; alkaryl; halogenated alkyl; heteroalkyl; aryl; heterocyclyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxyalkyl; aminoalkyl; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; acylamino; hydroxyl; thiol; thioalkyl; alkoxy; alkylthio; alkoxyalkyl; aryloxy; arylalkoxy; acyloxy; nitro; carbamoyl; trifluoromethyl; phenoxy; benzyloxy; phosphonic acid; phosphate ester; sulfonic acid (—SO 3 H); sulfonate ester; sulfonamide; alkaryl; arylalkyl; carbamate; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; alkylthio; heteroalkyl; alkyltriphenylphosphonium; heterocyclyl; ketone (═O); ether (—OR10); and ester (—COOR11 and —OC(═O)R11), and 
 wherein R10 and R11 are independently or jointly selected from the group consisting of a (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers; and alkynyl, 
 X is selected from N or C, 
 A is single bond or double bond, 
 Q is selected from N or C, 
 M is selected from O or C, and 
 wherein R2 is selected from: 
 
       
         
           
           
               
               
           
         
         wherein R6 and R7 are independently or jointly selected from O or absent; 
         R8 and R9 are independently or jointly selected from the group consisting of H; F; Cl; Br; I; OH; CN; (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers thereof; alkynyl; aralkyl; alkaryl; halogenated alkyl; heteroalkyl; aryl; heterocyclyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxyalkyl; aminoalkyl; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; acylamino; hydroxyl; thiol; thioalkyl; alkoxy; alkylthio; alkoxyalkyl; aryloxy; arylalkoxy; acyloxy; nitro; carbamoyl; trifluoromethyl; phenoxy; benzyloxy; phosphonic acid; phosphate ester; sulfonic acid (—SO 3 H); sulfonate ester; sulfonamide; alkaryl; arylalkyl; carbamate; amino; alkylamino; arylamino; dialkylamino; alkylarylamino; diarylamino; alkylthio; heteroalkyl; alkyltriphenylphosphonium; heterocyclyl; ketone (═O); ether (—OR10); and ester (—COOR11 and —OC(═O)R11), 
         or R8 and R9 are optionally bonded together to form a four-, five-, or six-membered heterocyclyl, cycloalkenyl, or cycloalkyl. and 
         wherein R10 and R11 are independently or jointly selected from the group consisting of a (C 1-4 )alkyl comprising methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl; (C 2-4 )alkenyl comprising ethenyl, propenyl, butenyl, where a double bond is optionally located at any position in the alkenyl carbon chain, and any alkenyl conformational isomers; and alkynyl, and 
         Z is selected from C or S. 
       
     
     
         6 . The method of  claim 5 , wherein the one or more compounds comprise: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         7 . The method of  claim 5 , wherein the microbial infections comprise staphylococcal infection. 
     
     
         8 . The method of  claim 5 , wherein the method reduces the production of pigment in  Staphylococcus aureus.    
     
     
         9 . The method of  claim 5 , wherein the microbial infections and/or related diseases or conditions comprise infections of the skin and soft tissue, bone and joint, surgical wound, indwelling devices, lung and heart valves. 
     
     
         10 . The method of  claim 5 , wherein said subject is a mammal. 
     
     
         11 . The method of  claim 5 , wherein said subject is human.