Use of isoxazoline compounds for treating demodicosis

Abstract

The present invention relates to methods of treating demodicosis by administering an isoxazoline compound of formula (I).

1 . Method of treating generalized demodicosis in mammals comprising administering an effective amount of an isoxazoline compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         R 1 =halogen, CF 3 , OCF 3 , CN, 
         n=integer from 0 to 3, 
         R 2 =C 1 -C 3 -haloalkyl, 
         T=5- or 6-membered ring, which is optionally substituted by one or more radicals Y, 
         Y=methyl, halomethyl, halogen, CN, NO 2 , NH 2 —C═S, or two adjacent radicals Y form together a chain; 
         Q=X—NR 3 R 4  or a 5-membered N-heteroaryl ring, which is optionally substituted by one or more radicals; 
         X=CH 2 , CH(CH 3 ), CH(CN), CO, CS, 
         R 3 =hydrogen, methyl, haloethyl, halopropyl, halobutyl, methoxymethyl, methoxyethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, N-phenyl-N-methyl-amino, haloethylaminocarbonylmethyl, haloethylaminocarbonylethyl, tetrahydrofuryl, methylaminocarbonylmethyl, (N,N-dimethylamino)-carbonylmethyl, propylaminocarbonylmethyl, cyclopropylaminocarbonylmethyl, propenylaminocarbonylmethyl, haloethylaminocarbonylcyclopropyl, 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein Z A =hydrogen, halogen, cyano, halomethyl (CF 3 ); 
         R 4 =hydrogen, ethyl, methoxymethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl, propylcarbonyl, cyclopropylcarbonyl, methoxycarbonyl, methoxymethylcarbonyl, aminocarbonyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, haloethylaminocarbonylmethyl, cyanomethylaminocarbonylmethyl, or haloethylaminocarbonylethyl; 
         or R 3  and R 4  together form a substituent selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         or a salt or solvate or N oxide thereof. 
       
     
     
         2 . The method according to  claim 1  wherein the isoxazoline compound of formula (I) is fluralaner. 
     
     
         3 . The method according to  claim 1  wherein the isoxazoline compound is administered once, twice or three times. 
     
     
         4 . The method according to  claim 1  comprising a single administration of the isoxazoline compound to a mammal. 
     
     
         5 . The method according to  claim 1  wherein the isoxazoline compound is administered to the mammal orally 
     
     
         6 . The method according to  claim 1  wherein the isoxazoline compound is administered to the mammal topically. 
     
     
         7 . The method according to  claim 1  wherein the isoxazoline compound is administered to the mammal parenterally by injection. 
     
     
         8 . The method according to  claim 1  wherein the mammal is a companion animal. 
     
     
         9 . The method according to  claim 1  wherein the companion animal is a dog. 
     
     
         10 . Method of controlling  Demodex  spp. mites in dogs after a single administration of an isoxazoline compound of formula (I). 
     
     
         11 . The method according to  claim 10  wherein the isoxazoline compound of formula (I) is fluralaner. 
     
     
         12 . The method according to  claim 10  wherein the  Demodex  spp. mites are controlled for at least 56 days. 
     
     
         13 . The method according to  claim 10  wherein the isoxazoline compound is administered to the mammal orally. 
     
     
         14 . The method according to  claim 10  wherein the isoxazoline compound is administered to the mammal topically. 
     
     
         15 . The method according to  claim 10  wherein the isoxazoline compound is administered to the mammal parenterally by injection. 
     
     
         16 . The method according to  claim 1  wherein the isoxazoline compound is afoxalaner. 
     
     
         17 . The method according to  claim 1  wherein the isoxazoline compound is sarolaner. 
     
     
         18 . The method according to  claim 1  comprising a single administration of 10-40 mg/kg bodyweight fluralaner to dogs that have been diagnosed with generalized demodicosis. 
     
     
         19 . The method of  claim 1 , where n is 1, 2 or 3. 
     
     
         20 . The method of  claim 1 , wherein R 2  is CF 3  or CF 2 Cl. 
     
     
         21 . The method of  claim 1 , wherein two adjacent radicals Y form together a three or four membered chain.