Non-halogenated phenyl substituted phenols, antimicrobial compositions containing the same, and methods of using the same

Abstract

A antimicrobial compound, compositions containing the same, and method of using the same for reducing the presence of microorganism on a substrate or in a fluid environment comprising an antimicrobial effective carrier and at least one antimicrobial compounds including non-halogenated phenyl substituted phenol compounds.

What is claimed is:  
     
         1 . A compound selected from the following formulas:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  and R 2  are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and  
 R 3  is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;  
 R 4  is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;  
 with the proviso that, 
 for compounds of Formula Ia, when R 1  is a C 1-8  n-alkyl group or a C 3-6  cycloalkyl group, each being optionally partially or fully substituted with a C 3-6  cycloalkyl group or a C 1-7  side chain alkyl group, and R 2  is hydrogen, then R 3  is not selected from the group consisting of a C 1-8  n-alkyl group and a C 3-6  cycloalkyl group, each being optionally partially or fully substituted with a C 3-6  cycloalkyl group or a C 1-7  side chain alkyl group;  
 for compounds of Formulas Ia through Ic, when R 1  and R 2  and R 4  are each hydrogen, then R 3  is not selected from the group consisting of hydrogen, a 4-alkyl group, or a 2-benzyloxy group; and  
 for compounds of Formula Ic, wherein each of R 1 , R 3  and R 4  is hydrogen, then R 2  is not selected from the group consisting of a methyl group, an ethyl group, or a tert-butyl group.  
 for compounds of Formula Ic, wherein each of R 1 , and R 4  is hydrogen, and R 3  is a 2-hydroxyl, then R 2  is not a tert-butyl group.  
 
 
     
     
         2 . The compound of  claim 1  wherein each of R 1  and R 2  is independently selected from the group consisting of straight or branched alkyl groups.  
     
     
         3 . The compound of  claim 1 , wherein each of R 1  and R 2  is a cycloalkyl group.  
     
     
         4 . An antimicrobial composition comprising an antimicrobial acceptable carrier and an effective antimicrobial amount of at least one compound selected from the following formulas:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  and R 2  are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and  
 R3 is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;  
 R 4  is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;  
 with the proviso that, 
 for compounds of Formula IIa, when R 1  is a C 1-8  n-alkyl group or a C 3-6  cycloalkyl group, each being optionally partially or fully substituted with a C 3-6  cycloalkyl group or a C 1-7  side chain alkyl group, and R 2  is hydrogen, then R 3  is not selected from the group consisting of a C 1-8  n-alkyl group and a C 3-6  cycloalkyl group, each being optionally partially or fully substituted with a C 3-6  cycloalkyl group or a C 1-7  side chain alkyl group; and  
 for compounds of Formulas IIa through IIc, when each of R 1 , R 2  and R 4  are each hydrogen, then R 3  is not hydrogen.  
 
 
     
     
         5 . The antimicrobial composition of  claim 4  wherein the antimicrobial effective carrier is selected from the group consisting of water, saline, alcohol, glycerin, propylene glycol, mineral oil, petrolatum and mixtures thereof.  
     
     
         6 . The antimicrobial composition of  claim 4  wherein the compound has the Formula IIa wherein each of R 2  and R 3  is hydrogen, and R 1  is selected from the group consisting of an alkyl group substituted with an aryl group; a cycloalkenyl group; benzyl substituted with an alkyl group; a cycloalkyl group optionally substituted with hydroxyl; and an aryl group optionally substituted with an alkyl group.  
     
     
         7 . The antimicrobial composition of  claim 6  wherein R 1  is selected from the group consisting of 1-phenylethyl, cyclohex-2-enyl, 3-methylbenzyl, phenyl, phenyl substituted with tert-butyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, and 4-hydroxycyclohexyl.  
     
     
         8 . The antimicrobial composition of  claim 4  wherein the compound has the Formula IIa wherein R 2  is hydrogen, and R 3  is tert-butyl, and R 1  is selected from the group consisting of hydrogen and phenyl.  
     
     
         9 . The antimicrobial composition of  claim 4  wherein the compound has the Formula IIa wherein each of R 1  and R 2  is hydrogen, and R 3  is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl.  
     
     
         10 . The antimicrobial composition of  claim 9  wherein R 3  is selected from the group consisting of tert-butyl, cyclohexyl, cyclopentyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.  
     
     
         11 . The antimicrobial composition of  claim 4 , wherein the compound has the Formula IIc wherein each of R 1 , R 3  and R 4  is hydrogen and R 2  is selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or a hydroxyl group; benzyl; an alkoxy group; a cycloalkenyl group; a cycloalkyl group optionally substituted with a hydroxyl group.  
     
     
         12 . The antimicrobial composition of  claim 11  wherein R 2  is selected from the group consisting of tert-butyl, benzyl, hexyloxy, cyclohex-2-enyl, cyclohexyl, 2 cyclohexylethyl, 1-methyl-1-ethylpropyl, ethyl, propyl, 5-hydroxypentyl, isopropyl, 1,1-dimethylpropyl, cyclopentyl, 1-methylbutyl, 2-hydroxycyclopentyl and 3-hydroxycyclopentyl.  
     
     
         13 . The antimicrobial composition of  claim 4  wherein the compound has the Formula IIc wherein each of R 1 , R 2  and R 4  is hydrogen, and R 3  is selected from the group consisting of a benzyloxy group or an alkyl group.  
     
     
         14 . The antimicrobial composition of  claim 13  wherein R 3  is tert-butyl or a benzyloxy group.  
     
     
         15 . The antimicrobial composition of  claim 4  wherein the compound has the Formula IIc wherein each of R 1  and R 4  is hydrogen, and R 3  is a hydroxyl, and R 2  is selected from the group consisting of a benzyl group or an alkyl group optionally substituted with a hydroxyl group.  
     
     
         16 . The antimicrobial composition of  claim 15  wherein R 2  is selected from the group consisting of tert-butyl, ethyl, isopropyl, benzyl, 4-hydroxybutyl, or hydroxymethyl.  
     
     
         17 . The antimicrobial composition of  claim 4  wherein the compound has the Formula IIc wherein each of R 1  and R 2  is hydrogen, R 3  is an alkoxy group, and R 4  is an alkyl group optionally substituted with hydroxyl.  
     
     
         18 . The antimicrobial composition of  claim 17 , wherein R 3  is a methoxy group and R 4  ia a hydroxymethyl group.  
     
     
         19 . The antimicrobial composition of  claim 4  wherein the compound has the Formula IIb wherein each of R 1  and R 2  is hydrogen, R 3  is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl.  
     
     
         20 . The antimicrobial composition of  claim 19  wherein R 3  is selected from the group consisting of tert-butyl, cyclohexyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyclopentyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.  
     
     
         21 . The antimicrobial composition of  claim 4  wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight of the total weight of the antimicrobial composition.  
     
     
         22 . The antimicrobial composition of  claim 21  wherein the antimicrobial effective amount is from about 0.001 to 5% by weight of the total weight of the antimicrobial composition.  
     
     
         23 . An oral composition comprising an orally acceptable carrier and an effective antimicrobial amount of at least one compound selected from the following formulas:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  and R 2  are each independently selected from the group consisting of hydrogen, an alkyl group optionally substituted with a cycloalkyl group or an aryl group; an alkenyl group; an alkoxy group; a cycloalkenyl group; an aryl group; benzyl optionally substituted with an alkyl group; and a cycloalkyl group, wherein any one of which said groups can optionally be substituted with hydroxyl; and  
 R3 is selected from the group consisting of hydrogen, a hydroxyl group, an alkyl group optionally substituted with hydroxyl, an aryl group, a benzyl group, a benzyloxy group, an alkoxy group, and a cycloalkyl group optionally substituted with hydroxyl;  
 R 4  is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;  
 with the proviso that, 
 for compounds of Formula IIa, when R 1  is a C 1-8  n-alkyl group or a C 3-6  cycloalkyl group, each being optionally partially or fully substituted with a C 3-6  cycloalkyl group or a C 1-7  side chain alkyl group, and R 2  is hydrogen, then R 3  is not selected from the group consisting of a C 1-8  n-alkyl group and a C 3-6  cycloalkyl group, each being optionally partially or fully substituted with a C 3-6  cycloalkyl group or a C 1-7  side chain alkyl group; and  
 for compounds of Formula IIa, when each of R 1 , R 2  and R 4  is a hydrogen, then R 3  is not hydrogen.  
 
 
     
     
         24 . The oral composition of  claim 23  wherein the orally acceptable carrier is selected from the group consisting of water, saline, alcohol, glycerin, propylene glycol, and mixtures thereof.  
     
     
         25 . The oral composition of  claim 23  wherein the compound has the Formula IIa wherein each of R 2  and R 3  is hydrogen, and R 1  is selected from the group consisting of an alkyl group substituted with an aryl group; a cycloalkenyl group; benzyl substituted with an alkyl group; a cycloalkyl group optionally substituted with hydroxyl; and an aryl group optionally substituted with an alkyl group.  
     
     
         26 . The oral composition of  claim 25  wherein R 1  is selected from the group consisting of 1-phenylethyl, cyclohex-2-enyl, 3-methylbenzyl, phenyl, phenyl substituted with tert-butyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, and 4-hydroxycyclohexyl.  
     
     
         27 . The oral composition of  claim 23  wherein the compound has the Formula IIa wherein R 2  is hydrogen, and R 3  is tert-butyl, and R 1  is selected from the group consisting of hydrogen and phenyl.  
     
     
         28 . The oral composition of  claim 23  wherein the compound has the Formula IIa wherein each of R 1  and R 2  is hydrogen, and R 3  is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl.  
     
     
         29 . The oral composition of  claim 28  wherein R 3  is selected from the group consisting of tert-butyl, cyclohexyl, cyclopentyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.  
     
     
         30 . The oral composition of  claim 23  wherein the compound has the Formula IIc wherein each of R 1 , R 3 , and R 4  is hydrogen and R 2  is selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or a hydroxyl group; benzyl; an alkoxy group; a cycloalkenyl group; a cycloalkyl group optionally substituted with a hydroxyl group.  
     
     
         31 . The oral composition of  claim 30  wherein R 2  is selected from the group consisting of tert-butyl, benzyl, hexyloxy, cyclohex-2-enyl, cyclohexyl, 2 cyclohexylethyl, 1-methyl-1-ethylpropyl, ethyl, propyl, 5-hydroxypentyl, isopropyl, 1,1-dimethylpropyl, cyclopentyl, 1-methylbutyl, 2-hydroxycyclopentyl and 3-hydroxycyclopentyl.  
     
     
         32 . The oral composition of  claim 23  wherein the compound has the Formula IIc wherein each of R 1 , R 2  and R 4  is hydrogen, and R 3  is selected from the group consisting of a benzyloxy or an alkyl group.  
     
     
         33 . The oral composition of  claim 32  wherein R 3  is tert-butyl or a benzyloxy group.  
     
     
         34 . The oral composition of  claim 23  wherein the compound has the Formula IIc wherein each of R 1  and R 3  is hydrogen, and R 2  is an alkyl group.  
     
     
         35 . The antimicrobial composition of  claim 34  wherein the alkyl group is tert-butyl.  
     
     
         36 . The oral composition of  claim 23 , wherein the compound has the Formula IIc wherein each of R 1  and R 4  is hydrogen, and R 3  is a hydroxyl, and R 2  is selected from the group consisting of a benzyl group or an alkyl group optionally substituted with a hydroxyl group.  
     
     
         37 . The oral composition of  claim 36  wherein R 2  is selected from the group consisting of tert-butyl, ethyl, isopropyl, benzyl, 4-hydroxybutyl, or hydroxymethyl.  
     
     
         38 . The oral composition of  claim 23  wherein the compound has the Formula IIc wherein each of R 1  and R 2  is hydrogen, R 3  is an alkoxy group, and R 4  is an alkyl group optionally substituted with hydroxyl.  
     
     
         39 . The antimicrobial composition of  claim 38 , wherein R 3  is a methoxy group and R 4  ia a hydroxymethyl group.  
     
     
         40 . The oral composition of  claim 23  wherein the compound has the Formula IIb wherein each of R 1  and R 2  is hydrogen, R 3  is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with a hydroxyl.  
     
     
         41 . The oral composition of  claim 40  wherein R 3  is selected from the group consisting of tert-butyl, cyclohexyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyclopentyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.  
     
     
         42 . The oral composition of  claim 23  wherein the compound has Formula IIb wherein R 1  is hydrogen, R 2  is phenyl, and R 3  is an alkyl group  
     
     
         43 . The oral composition of  claim 42  wherein R 3  is tert-butyl.  
     
     
         44 . The oral composition of  claim 23  wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight of the total weight of the oral composition.  
     
     
         45 . The oral composition of  claim 44  wherein the antimicrobial effective amount is from about 0.001 to 5% by weight of the total weight of the oral composition.  
     
     
         46 . The oral composition of  claim 23  further comprising at least one essential oil.  
     
     
         47 . The oral composition of  claim 46  wherein the at least one essential oil is selected from the group consisting of thymol, menthol, eucalyptol, methyl salicylate, and combinations thereof.  
     
     
         48 . The oral composition of  claim 47 , wherein the essential oil comprises: 
 an amount of from about 0.005 to 0.5% menthol;    an amount of from about 0.005 to 0.5% eucalyptol;    an amount of from about 0.005 to 0.5% methyl salicytate; and    an amount of from about 0.005 to 0.5% thymol.    
     
     
         49 . A method of reducing the presence of microorganisms on a substrate comprising treating the substrate with an effective amount of the antimicrobial composition of  claim 4 .  
     
     
         50 . The method of  claim 49  wherein the antimicrobial effective carrier is selected from the group consisting of water, saline, alcohol, glycerin, propylene glycol, mineral oil, petrolatum, and mixtures thereof.  
     
     
         51 . The method of  claim 50  wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight.  
     
     
         52 . The method of  claim 49  wherein the antimicrobial effective amount is from about 0.001 to 5% by weight.  
     
     
         53 . The method of  claim 49  wherein the antimicrobial composition is in the form of a member selected from the group consisting of a deodorant, a soap, an ointment, and a cream.  
     
     
         54 . A method of reducing the presence of microorganisms in an oral cavity comprising administering into the oral cavity a microorganism-reducing effective amount of the oral composition of  claim 23 .  
     
     
         55 . The method of  claim 54  wherein the orally acceptable carrier is selected from the group consisting of water, saline, alcohol, glycerin, propylene glycol, and mixtures thereof.  
     
     
         56 . The method of  claim 54  wherein the compound has the Formula IIa wherein each of R 2  and R 3  is hydrogen, and R 1  is selected from the group consisting of an alkyl group substituted with an aryl group; a cycloalkenyl group; benzyl substituted with an alkyl group; a cycloalkyl group optionally substituted with hydroxyl; and an aryl group optionally substituted with an alkyl group.  
     
     
         57 . The method of  claim 56  wherein R 1  is selected from the group consisting of 1-phenylethyl, cyclohex-2-enyl, 3-methylbenzyl, phenyl, phenyl substituted with tert-butyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, and 4-hydroxycyclohexyl.  
     
     
         58 . The method of  claim 54  wherein the compound has the Formula IIa wherein R 2  is hydrogen, and R 3  is tert-butyl, and R 1  is selected from the group consisting of hydrogen and phenyl.  
     
     
         59 . The method of  claim 54  wherein the compound has the Formula IIa wherein each of R 1  and R 2  is hydrogen, and R 3  is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl.  
     
     
         60 . The method of  claim 59  wherein R 3  is selected from the group consisting of tert-butyl, cyclohexyl, cyclopentyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.  
     
     
         61 . The method of  claim 54  wherein the compound has the Formula IIb wherein R 1  is hydrogen, R 2  is phenyl, and R 3  is an alkyl group.  
     
     
         62 . The method of  claim 61  wherein the alkyl group is tert-butyl.  
     
     
         63 . The oral composition of  claim 54  wherein the compound has the Formula IIb wherein each of R 1  and R 2  is hydrogen, R 3  is selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with a hydroxyl.  
     
     
         64 . The oral composition of  claim 63  wherein R 3  is selected from the group consisting of tert-butyl, cyclohexyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyclopentyl, 2-hydroxycyclopentyl, and 3-hydroxycyclopentyl.  
     
     
         65 . The method of  claim 54 , wherein the compound has Formula IIc wherein each R 1 , R 3  and R 4  is hydrogen and R 2  is selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl or a hydroxyl; a benzyl, an alkoxy group; a cycloalkenyl group; a cycloalkyl group optionally substituted with a hydroxyl.  
     
     
         66 . The method of  claim 65  wherein R 2  is selected from the group consisting of tert-butyl, benzyl, hexyloxy, cyclohex-2-enyl, cyclohexyl, 2 cyclohexylethyl, 1-methyl-1-ethylpropyl, ethyl, propyl, 5-hydroxypentyl, isopropyl, 1,1-dimethylpropyl, cyclopentyl, 1-methylbutyl, 2-hydroxycyclopentyl and 3-hydroxycyclopentyl.  
     
     
         67 . The method of  claim 54  wherein the compound has the Formula IIc wherein each of R 1 , R 2  and R 4  is hydrogen, and R 3  is selected from the group consisting of benzyloxy or an alkyl group.  
     
     
         68 . The method of  claim 67  wherein R 3  is tert-butyl or benzyloxy group.  
     
     
         69 . The method of  claim 54 , wherein the compound has the Formula IIc wherein each of R 1  and R 4  is hydrogen, and R 3  is a hydroxyl, and R 2  is selected from the group consisting of a benzyl group or an alkyl group optionally substituted with a hydroxyl group.  
     
     
         70 . The method of  claim 69  wherein R 2  is selected from the group consisting of tert-butyl, ethyl, isopropyl, benzyl, 4-hydroxybutyl, or hydroxymethyl.  
     
     
         71 . The method of  claim 54  wherein the compound has the Formula IIc wherein each of R 1  and R 2  is hydrogen, R 3  is an alkoxy group, and R 4  is an alkyl group optionally substituted with hydroxyl.  
     
     
         72 . The method of  claim 71 , wherein R 3  is a methoxy group and R 4  ia a hydroxymethyl group.  
     
     
         73 . The method of  claim 54  wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight.  
     
     
         74 . The method of  claim 73  wherein the antimicrobial effective amount is from about 0.001 to 5% by weight.  
     
     
         75 . The method of  claim 54  wherein the oral composition is in the form of a member selected from the group consisting of a mouthrinse, a dentifrice, a chewing gum, a dispersible oral film, a lozenge, and an oral film forming dentifrice.