Non-halogenated naphthol compounds, antimicrobial compositions containing the same, and methods of using the same

Abstract

An antimicrobial compound, composition containing such compound, and method of use of the same for reducing the presence of microorganism on a substrate or in a fluid environment comprising an antimicrobial effective carrier and one or more essential antimicrobial compounds including non-halogenated naphthol compounds.

1 . An antimicrobial composition comprising an effective amount of at least one antimicrobial agent having the Formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 one of R 1  and R 2  is hydroxyl, and the other of R 1  and R 2 , and each of R 3 , R 4 , and R 5  are independently selected from the group consisting of hydrogen; hydroxyl; an alkyl group optionally phenyl in which the phenyl may be substituted with a member selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl; a cycloalkyl group optionally substituted with hydroxyl; phenyl; phenyl substituted with a member selected from the group consisting of an alkyl group optionally substituted with hydroxyl, a cycloalkyl group optionally substituted with hydroxyl, and an alkoxy group; and  
                     
 wherein R x  is a member selected from the group consisting of an alkyl group, benzyl, and phenyl;  
 and each of R 6  and R 7  are selected from the group consisting of straight chain or branched alkyl optionally substituted with hydroxyl, and benzyl or phenyl optionally substituted with hydroxyl, alkyl, or alkoxy groups;  
 with the proviso that: 
 when R 1  is hydroxyl, then R 2 , R 3 , R 4 , and R 5  are not all hydrogen;  
 when R 2  is hydroxyl, then R 1 , R 3 , R 4 , and R 5  are not all hydrogen;  
 when R 1  is hydroxyl, and each of R 3  and R 5  is hydrogen, then R 2  and R 4  are not independently selected from methyl and hydrogen;  
 when R 2  is hydroxyl, and each of R 1 , R 3 , R 4  is hydrogen, then R 5  is not methyl;  
 when R 1  is hydroxyl, and each of R 3 , R 4  and R 5  is hydrogen, then R 2  is not isobutyl; and  
 when R 2  is hydroxyl and each of R 3 , R 4 , and R 5  is hydrogen, then R 1  is not selected from the group consisting of isopropyl and isobutyl; and  
 
 an antimicrobial effective carrier.  
 
     
     
         2 . The antimicrobial composition of  claim 1  wherein the antimicrobial effective carrier is selected from the group consisting of water, saline, alcohol, glycerine, propylene glycol, mineral oil, petrolatum, and mixtures thereof.  
     
     
         3 . The antimicrobial composition of  claim 1  wherein the compound has the formula (IIa) wherein each of R 3 , R 4 , and R 5  is hydrogen.  
     
     
         4 . The antimicrobial composition of  claim 3  wherein R 1  is hydroxyl.  
     
     
         5 . The antimicrobial composition of  claim 4  wherein R 2  is an alkyl group.  
     
     
         6 . The antimicrobial composition of  claim 5  wherein R 2  is tert-butyl.  
     
     
         7 . The antimicrobial composition of  claim 3  wherein R 2  is hydroxyl.  
     
     
         8 . The antimicrobial composition of  claim 7  wherein R 1  is selected from the group consisting of an alkyl group optionally substituted with hydroxyl, a cycloalkyl group optionally substituted with hydroxyl, a phenyl group optionally substituted with hydroxyl, and benzyl.  
     
     
         9 . The antimicrobial composition of  claim 8  wherein R 1  is selected from the group consisting of isopropyl, butyl, tert-butyl, hexyl, cyclohexyl, phenyl and benzyl.  
     
     
         10 . The antimicrobial composition of  claim 1  wherein the compound has the formula (IIa) wherein R 1  is hydroxyl, and R 3  and R 5  are each hydrogen.  
     
     
         11 . The antimicrobial composition of  claim 10  wherein R 2  is hydrogen and R 4  is an alkyl group optionally substituted with phenyl.  
     
     
         12 . The antimicrobial composition of  claim 11  wherein R 4  is selected from the group consisting of tert-butyl and benzyl.  
     
     
         13 . The antimicrobial composition of  claim 10  wherein each of R 2  and R 4  is tert-butyl.  
     
     
         14 . The antimicrobial composition of  claim 1  wherein the compound has the formula (IIa) wherein each of R 1 , R 4 , and R 5  is hydrogen, and R 3  is selected from the group consisting of an alkyl group and an alkenyl group.  
     
     
         15 . The antimicrobial composition of  claim 14  wherein R 3  is isopropyl.  
     
     
         16 . The antimicrobial composition of  claim 8  wherein R 1  is selected from the group consisting of 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, 3-hydroxycyclopentyl, 4-hydroxycyclopentyl, 2-hydroxycyclophenyl, 3-hydroxycyclophenyl, and 4-hydroxycyclophenyl  
     
     
         17 . The antimicrobial composition of  claim 4  wherein R 2  is selected from the group consisting of 2-hydroxyphenyl and 3-hydroxyphenyl.  
     
     
         18 . The antimicrobial composition of  claim 1  wherein the compound has the formula (IIa) wherein R 2  is hydroxyl, each of R 1  and R 4  is hydrogen, R 3  is an alkyl group, and R 5  is selected from the group consisting of an alkyl group, an alkyl group substituted with phenyl, a cycloalkenyl group, and a benzyl group optionally substituted with an alkyl group.  
     
     
         19 . The antimicrobial composition of  claim 18  wherein R 3  is isopropyl and R 5  is selected from the group consisting of 1-methyl-butyl, 1-phenyl-ethyl, cyclohex-2-enyl, 1-ethyl-1-methyl-propyl, and 3-methyl-benzyl.  
     
     
         20 . The antimicrobial composition of  claim 1  wherein the compound has the formula (IIa) wherein R 2  is hydroxyl, each of R 3  and R 4  is hydrogen, R 1  is an alkyl group, and R 5  is selected from the group consisting of an alkyl group and a benzyl group optionally substituted with an alkyl group.  
     
     
         21 . The antimicrobial composition of  claim 20  wherein R 1  is isopropyl, and R 5  is selected from the group consisting of 1-ethyl-1-methyl-propyl, 3-methyl-benzyl, and tert-butyl.  
     
     
         22 . The antimicrobial composition of  claim 1  wherein the antimicrobial agent is selected from the group consisting of 3-isopropyl-6-(1-methyl-butyl)-naphthalen-2-ol, 3-isopropyl-6-(1-phenyl-ethyl)-naphthalen-2-ol, 1-(4-hydroxynaphthyl)octan-1-one, 6-(1-ethyl-1-methyl-propyl)-1-isopropyl-naphthalen-2-ol, 6-(tert-butyl)-1-isoproyl-naphthalen-2-ol, 6-(3-cyclohexenyl)-2-naphthol, 1-(6-hydroxy-2-naphthyl)hexan-1-one, 1-isopropyl-6-(3-methyl-benzyl)-naphthalen-2-ol, 1-(4-hydroxynaphthyl)hexan-1-one, 6-cyclohex-2-enyl-3-isopropyl-naphthalen-2-ol, 6-cyclopentyl-2-naphthol, 6-(1-ethyl-1-methyl-propyl)-3-isopropyl-naphthalen-2-ol, 3-isopropyl-6-(3-methyl-benzyl)naphthalen-2-ol, 6-(tert-butyl)-1-isopropyl-naphthalen-2-ol, 6-(3-methyl-benzyl)-2-naphthol, 4-(2-hydroxycyclohexyl)-1-naphthol, 4-(3-hydroxycyclohexyl)-1-naphthol, 1-(2-hydroxycyclohexyl)-2-naphthol, 1-(3-hydroxycyclohexyl)-2-naphthol, 1-(4-hydroxycyclohexyl)-2-naphthol, 1-cyclopentyl-2-naphthol, 1-(2-hydroxycyclopentyl)-2-naphthol, 1-(3-hydroxycyclopentyl)-2-naphthol, 4-(2-hydroxycyclopentyl)-1-naphthol, and 4-(3-hydroxycyclopentyl)-1-naphthol.  
     
     
         23 . The antimicrobial composition of  claim 1  wherein the antimicrobial effective amount is from about 0.0001% to 10.0% by weight based on the total weight of the antimicrobial composition.  
     
     
         24 . The antimicrobial composition of  claim 23  wherein the antimicrobial effective amount is from about 0.001% to 5.0% by weight.  
     
     
         25 . An oral composition comprising an antimicrobial effective amount of at least one antimicrobial agent having the Formula  
       
         
           
           
               
               
           
         
       
       wherein 
 one of R 1  and R 2  is hydroxyl, and the other of R 1  and R 2 , and each of R 3 , R 4 , and R 5  are independently selected from the group consisting of hydrogen; hydroxyl; an alkyl group optionally substituted with hydroxyl; an alkenyl group; a cycloalkenyl group; an alkyl group substituted with phenyl in which the phenyl may be substituted with a member selected from the group consisting of an alkyl group optionally substituted with hydroxyl and a cycloalkyl group optionally substituted with hydroxyl; a cycloalkyl group optionally substituted with hydroxyl; phenyl; phenyl substituted with a member selected from the group consisting of an alkyl group optionally substituted with hydroxyl, a cycloalkyl group optionally substituted with hydroxyl, and an alkoxy group; and  
                     
 wherein R x  is a member selected from the group consisting of an alkyl group, benzyl, and phenyl;  
 and each of R 6  and R 7  are selected from the group consisting of straight chain or branched alkyl optionally substituted with hydroxyl, and benzyl or phenyl optionally substituted with hydroxyl, alkyl, or alkoxy groups;  
 with the proviso that: 
 when R 1  is hydroxyl, then R 2 , R 3 , R 4 , and R 5  are not all hydrogen;  
 when R 2  is hydroxyl, then R 1 , R 3 , R 4 , and R 5  are not all hydrogen; and 
 an orally acceptable carrier.  
 
 
 
     
     
         26 . The oral composition of  claim 25 , wherein the orally acceptable carrier is selected from the group consisting of water, saline, alcohol, glycerine, propylene glycol, and mixtures thereof.  
     
     
         27 . The oral composition of  claim 25  wherein the compound has the formula (IIIa) wherein each of R 3 , R 4 , and R 5  is hydrogen.  
     
     
         28 . The oral composition of  claim 27  wherein R 1  is hydroxyl.  
     
     
         29 . The oral composition of  claim 28  wherein R 2  is an alkyl group.  
     
     
         30 . The oral composition of  claim 29  wherein R 2  is tert-butyl.  
     
     
         31 . The oral composition of  claim 27  wherein R 2  is hydroxyl.  
     
     
         32 . The oral composition of  claim 31  wherein R 1  is selected from the group consisting of an alkyl group, a cycloalkyl group optionally substituted with hydroxyl, phenyl optionally substituted with hydroxyl, and benzyl.  
     
     
         33 . The oral composition of  claim 32  wherein R 1  is selected from the group consisting of isopropyl, butyl, tert-butyl, hexyl, cyclohexyl, phenyl and benzyl.  
     
     
         34 . The oral composition of  claim 25  wherein the compound has the formula (IIIa) wherein R 1  is hydroxyl, and R 3  and R 5  are each hydrogen.  
     
     
         35 . The oral composition of  claim 34  wherein R 2  is hydrogen and R 4  is an alkyl group optionally substituted with phenyl.  
     
     
         36 . The oral composition of  claim 35  wherein R 4  is selected from the group consisting of tert-butyl and benzyl.  
     
     
         37 . The oral composition of  claim 34  wherein each of R 2  and R 4  is tert-butyl.  
     
     
         38 . The oral composition of  claim 25  wherein the compound has the formula (IIIa) wherein each of R 1 , R 4 , and R 5  is hydrogen, R 2  is hydroxyl and R 3  is an alkyl group.  
     
     
         39 . The oral composition of  claim 38  wherein R 3  is isopropyl.  
     
     
         40 . The oral composition of  claim 32  wherein R 1  is selected from the group consisting of 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, 3-hydroxycyclopentyl, cyclopentyl, 2-hydroxyphenyl, 3-hydroxyphenyl, and 4-hydroxyphenyl.  
     
     
         41 . An oral composition of  claim 25  wherein the compound has the formula (IIIa) wherein R 1  is hydroxyl, each of R 3 , R 4 , and R 5  is hydrogen, and R 2  is selected from the group consisting of 2-hydroxyphenyl and 3-hydroxyphenyl.  
     
     
         42 . The oral composition of  claim 25  wherein the compound has the formula (IIIa) wherein R 2  is hydroxyl, each of R 1  and R 4  is hydrogen, R 3  is an alkyl group, and R 5  is selected from the group consisting of an alkyl group, an alkyl group substituted with phenyl, a cycloalkenyl group, and benzyl substituted with an alkyl group.  
     
     
         43 . The oral composition of  claim 42  wherein R 3  is isopropyl and R 5  is selected from the group consisting of 1-methyl-butyl, 1-phenyl-ethyl, cyclohex-2-enyl, 1-ethyl-1-methyl-propyl, and 3-methyl-benzyl.  
     
     
         44 . The oral composition of  claim 25  wherein the compound has the formula (IIIa) wherein R 2  is hydroxyl, each of R 3  and R 4  is hydrogen, R 1  is an alkyl group, and R 5  is selected from the group consisting of an alkyl group and benzyl substituted with an alkyl group.  
     
     
         45 . The oral composition of  claim 44  wherein R 1  is isopropyl, and R 5  is selected from the group consisting of 1-ethyl-1-methyl-propyl, 3-methyl-benzyl, and tert-butyl.  
     
     
         46 . The oral composition of  claim 25  wherein the antimicrobial agent is selected from the group consisting of 3-isopropyl-6-(1-methyl-butyl)-naphthalen-2-ol, 3-isopropyl-6-(1-phenyl-ethyl)-naphthalen-2-ol, 1-(4-hydroxynaphthyl)octan-1-one, 6-(1-ethyl-1-methyl-propyl)-1-isopropyl-naphthalen-2-ol, 6-(tert-butyl)-1-isoproyl-naphthalen-2-ol, 6-(3-cyclohexenyl)-2-naphthol, 1-(6-hydroxy-2-naphthyl)hexan-1-one, 1-isopropyl-6-(3-methyl-benzyl)-naphthalen-2-ol, 1-(4-hydroxynaphthyl)hexan-1-one, 6-cyclohex-2-enyl-3-isopropyl-naphthalen-2-ol, 6-cyclopentyl-2-naphthol, 6-(1-ethyl-1-methyl-propyl)-3-isopropyl-naphthalen-2-ol, 3-isopropyl-6-(3-methyl-benzyl)naphthalen-2-ol, 6-(tert-butyl)-1-isopropyl-naphthalen-2-ol, 6-(3-methyl-benzyl)-2-naphthol, 4-(2-hydroxycyclohexyl)-1-naphthol, 4-(3-hydroxycyclohexyl)-1-naphthol, 1-(2-hydroxycyclohexyl)-2-naphthol, 1-(3-hydroxycyclohexyl)-2-naphthol, 1-(4-hydroxycyclohexyl)-2-naphthol, 1-cyclopentyl-2-naphthol, 1-(2-hydroxycyclopentyl)-2-naphthol, 1-(3-hydroxycyclopentyl)-2-naphthol, 4-(2-hydroxycyclopentyl)-1-naphthol, and 4-(3-hydroxycyclopentyl)-1-naphthol.  
     
     
         47 . The oral composition of  claim 25  wherein the antimicrobial effective amount is from about 0.0001% to 10.0% by weight based on the total weight of the antimicrobial composition.  
     
     
         48 . The oral composition of  claim 47  wherein the antimicrobial effective amount is from about 0.001% to 5.0% by weight.  
     
     
         49 . The oral composition of  claim 25  further comprising at least one essential oil wherein at least one essential oil is selected from the group consisting of thymol, menthol, eucalyptol, methyl salicylate, and combinations thereof.  
     
     
         50 . The oral composition of  claim 49  wherein the essential oils comprise: 
 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 salicylate; and    an amount of from about 0.005 to 0.5% thymol.    
     
     
         51 . The oral composition of  claim 25  further comprising an antimicrobial enhancing agent in an amount of from about 0.05% to 5% by weight.  
     
     
         52 . The oral composition of  claim 51  wherein the antimicrobial enhancing agent includes an average molecular weight of from about 100 to about 5,000,000.  
     
     
         53 . The oral composition of  claim 51  wherein the antimicrobial enhancing agent is an anionic polymer containing one or more delivery-enhancing groups and retention-enhancing groups.  
     
     
         54 . The oral composition of  claim 53  wherein the antimicrobial enhancing agent is an anionic polycarboxylate.  
     
     
         55 . A method of reducing the presence of microorganisms on a substrate comprising treating the substrate with an antimicrobial effective amount of the antimicrobial composition of  claim 1 .  
     
     
         56 . The method of  claim 55  wherein the antimicrobial effective carrier is selected from the group consisting of water, saline, alcohol, glycerine, propylene glycol, mineral oil, petrolatum, and mixtures thereof.  
     
     
         57 . A method of reducing the presence of microorganisms in an oral cavity comprising administering into the oral cavity an antimicrobial effective amount of the oral composition of  claim 25 .  
     
     
         58 . The method of  claim 57  wherein the antimicrobial effective amount is from about 0.0001 to 10% by weight.  
     
     
         59 . The method of  claim 58  wherein the antimicrobial effective amount is from about 0.001 to 5% by weight.  
     
     
         60 . The method of  claim 59  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 lozenge, a dispersible oral film, and an oral film forming dentifrice.  
     
     
         61 . Compounds of Formula  
       
         
           
           
               
               
           
         
       
       wherein 
 one of R 1  and R 2  is hydroxyl, and the other of R 1  and R 2  is selected from the group consisting of hydrogen, an alkyl group optionally substituted with hydroxyl, a cycloalkyl group optionally substituted with hydroxyl, and an hydroxyphenyl group;  
 R 3  is selected from the group consisting of hydrogen and an alkyl group optionally substituted with hydroxyl;  
 R 4  is selected from the group consisting of hydrogen, a C 2  to C 6  straight chain or branched alkyl group optionally substituted with hydroxyl, a hydroxycycloalkyl group, and  
                     
 wherein R x  is an alkyl group;  
 R 5  is selected from hydrogen, an alkyl group optionally substituted with hydroxyl, a cycloalkyl group, a cycloalkenyl group, an alkyl group substituted with phenyl, benzyl substituted with an alkyl group, and  
                     
 wherein R x  is an alkyl group;  
 each of R 6  and R 7  are selected from the group consisting of straight chain or branched alkyl optionally substituted with hydroxyl, and benzyl or phenyl optionally substituted with hydroxyl, alkyl, or ‘alkoxy’ groups;  
 with the proviso that: 
 when R 1  is hydroxyl, then R 2 , R 3 , R 4 , and R 5  are not all hydrogen;  
 when R 2  is hydroxyl, then R 1 , R 3 , R 4 , and R 5  are not all hydrogen;  
 when R 2  is hydroxyl, then R 5  is not methyl;  
 when R 2  is hydroxyl and each of R 3 , R 4 , and R 5  is hydrogen, then R 1  is not selected from the group consisting of isopropyl and isobutyl;  
 when R 1  is hydroxyl and each of R 3 , R 4  and R 5  is hydrogen, then R 2  is not 4-hydroxyphenyl; and  
 
 when R 1  is hydroxyl and each of R 3 , and R 5  is hydrogen, then R 2  and R 4  are not both tert-butyl;  
 with the further proviso that R 6  and R 7  are not both tert-butyl.  
 
     
     
         62 . The compound of  claim 61  wherein the compound has the formula (Ia) wherein R 1  is hydroxyl, each of R 2 , R 3 , and R 4  is hydrogen, and R 5  is selected from the group consisting of a hydroxycycloalkyl group and  
       
         
           
           
               
               
           
         
       
       wherein Rx is an alkyl group.  
     
     
         63 . The compound of  claim 62  wherein R 5  is selected from the group consisting of 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, 3-hydroxycyclopentyl, and  
       
         
           
           
               
               
           
         
       
       wherein R x  is selected from the group consisting of n-heptyl and n-pentyl.  
     
     
         64 . The compound of  claim 61  wherein the compound has the formula (Ia) wherein R 2  is hydroxyl, each of R 3 , R 4 , and R 5  is hydrogen, and R 1  is selected from the group consisting of a cycloalkyl group optionally substituted with hydroxyl and an hydroxyphenyl group.  
     
     
         65 . The compound of  claim 64  wherein R 1  is selected from the group consisting of 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl, 3-hydroxycyclopentyl, cyclopentyl, 2-hydroxyphenyl, 3-hydroxyphenyl, and 4-hydroxyphenyl.  
     
     
         66 . The compound of  claim 61  wherein the compound has the formula (Ia) wherein R 2  is hydroxyl, each of R 1  and R 4  is hydrogen, R 3  is an alkyl group, and R 5  is selected from the group consisting of an alkyl group, an alkyl group substituted with phenyl, a cycloalkenyl group, and benzyl substituted with an alkyl group.  
     
     
         67 . The compound of  claim 66  wherein R 3  is isopropyl and R 5  is selected from the group consisting of 1-methyl-butyl, 1-phenyl-ethyl, cyclohex-2-enyl, 1-ethyl-1-methyl-propyl, and 3-methyl-benzyl.  
     
     
         68 . The compound of  claim 61  wherein the compound has the formula (Ia) wherein R 2  is hydroxyl, each of R 3  and R 4  is hydrogen, R 1  is an alkyl group, and R 5  is selected from the group consisting of an alkyl group and benzyl substituted with an alkyl group.  
     
     
         69 . The compound of  claim 68  wherein R 1  is isopropyl, and R 5  is selected from the group consisting of 1-ethyl-1-methyl-propyl, 3-methyl-benzyl, and tert-butyl.  
     
     
         70 . The compound of  claim 61  wherein the compound has the formula (Ia) wherein R 2  is hydroxyl, each of R 1 , R 3 , and R 4  is hydrogen, and R 5  is selected from the group consisting of a cycloalkenyl group, a cycloalkyl group, benzyl substituted with an alkyl group, and  
       
         
           
           
               
               
           
         
       
       wherein R x  is an alkyl group.  
     
     
         71 . The compound of  claim 70  wherein R 5  is selected from the group consisting of 3-cyclohex-2-enyl, cyclopentyl, 3-methyl-benzyl, and  
       
         
           
           
               
               
           
         
       
       wherein R x  is n-pentyl.  
     
     
         72 . A compound of  claim 60  wherein the compound has the formula (Ia) wherein R 1  is hydroxyl, each of R 3 , R 4 , and R 5  is hydrogen, and R 2  is selected from the group consisting of 2-hydroxyphenyl and 3-hydroxyphenyl.  
     
     
         73 . An antimicrobial composition of  claim 1  wherein the antimicrobial agent has the formula (IIb) wherein R 1  is hydroxyl and R 6  and R 7  are each independently selected from the group consisting of isopropyl, tert-butyl, phenyl and benzyl.  
     
     
         74 . A oral composition of  claim 25  wherein the antimicrobial agent has the formula (IIIb) wherein R 1  is hydroxyl and R 6  and R 7  are each independently selected from the group consisting of isopropyl, tert-butyl, phenyl and benzyl.  
     
     
         75 . A compound of  claim 60  wherein the compound has the formula (Ib) wherein R 1  is hydroxyl and R 6  and R 7  are each independently selected from the group consisting of isopropyl, tert-butyl, phenyl and benzyl.