US2012295931A1PendingUtilityA1

Spiroindoline compounds for use as anthelminthics

Assignee: LUTZ JUERGENPriority: Feb 5, 2010Filed: Feb 4, 2011Published: Nov 22, 2012
Est. expiryFeb 5, 2030(~3.5 yrs left)· nominal 20-yr term from priority
A61P 33/10A61K 31/444A61K 45/06C07D 471/10A61K 31/438A61P 33/00Y02A50/30
38
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Claims

Abstract

This invention relates to spiroindoline compounds for the treatment of helminth infections and the treatment of parasitosis, such as caused by helminth infections. This invention also relates to uses of the compounds to make medicaments and treatments comprising the administration of the compounds to animals in need of the treatments. Moreover this invention relates to pharmaceutical compositions and kits comprising the compounds.

Claims

exact text as granted — not AI-modified
1 . A pharmaceutical composition comprising
 a) one or more compounds of the formula (I) and pharmaceutically acceptable solvates, N-oxides and salts thereof,   
       
         
           
           
               
               
           
         
         wherein 
         Y=O, S; 
         Q=—CH 2 —CH(CH 3 )—, —CH 2 —CH 2 —O, —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH═CH—, —CH 2 —CH 2 —CH 2 —; 
         R 1 =H, F, Cl, CH 3 , OCH 3 , CF 3 ; 
         R 2 =H, F, Cl, CH 3 , OCH 3 , CF 3 ; 
         A 1 =H, halogen, C 1 -C 4 -alkyl; 
         A 2 =H, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, wherein C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkylthio are optionally perfluorinated; 
         A 3 =H, halogen, C 1 -C 4 -alkyl; 
         A 4 =H, halogen, C 1 -C 4 -alkyl; 
         B 1 =H, F, Cl, CH 3 , CF 3 ; 
         B 2 =H, F, Cl, CH 3 , CF 3 , NO 2 ; 
         B 3 =H, F, Cl, CH 3 , CF 3 , CN, OCH 3 , OCF 3 ; 
         B 4 =H, F, Cl, CH 3 , CF 3 ; 
         B 5 =H, F, Cl, CH 3 , CF 3   − ; and 
         b) one or more pharmaceutically acceptable excipients, and/or one or more pharmaceutically acceptable active ingredients which differ in structure from component a). 
       
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein in formula (I)
 Y=O, S;   Q=—CH 2 —CH(CH 3 )—, —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH═CH—, —CH 2 —CH 2 —CH 2 —; preferably —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH 2 —CH 2 —CH 2 —O—, —CH 2 —CH═CH—;   R 1 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;   R 2 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;   A 1 =H, halogen, C 1 -C 4 -alkyl;   A 2 =H, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, wherein C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkylthio are optionally perfluorinated;   A 3 =H, halogen, C 1 -C 4 -alkyl;   A 4 =H, halogen, C 1 -C 4 -alkyl;   B 1 =H, F, Cl, CH 3 , CF 3 ;   B 2 =H, F, Cl, CH 3 , CF 3 , NO 2 ;   B 3 =H, F, Cl, CH 3 , CF 3 , CN, OCH 3 , OCF 3 ;   B 4 =H, F, Cl, CH 3 , CF 3 ;   B 5 =H, F, Cl, CH 3 , CF 3 .   
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein in formula (I),
 Y=O, S, preferably O;   Q=—CH 2 —CH═CH—;   R 1 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;   R 2 =H, F, Cl, CH 3 , OCH 3 , CF 3 ;   A 1 =H, Cl;   A 2 =H, F, Cl, Br, CH 3 , OCH 3 , OCF 3 , CF 3 , SCF 3 ;   A 3 =H, Cl;   A 4 =H, Cl;   B 1 =H, F, Cl, CH 3 , CF 3 ;   B 2 =H, F, Cl, CH 3 , CF 3 ;   B 3 =H, F, Cl, CH 3 , CF 3 , CN, OCH 3 , OCF 3 ;   B 4 =H, F, Cl, CH 3 , CF 3 ;   B 5 =H, F, Cl, CH 3 , CF 3 .   
     
     
         4 . The pharmaceutical composition according to  claim 1  wherein in formula (I)
 a) at least one of the radicals R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , B 5  is different from hydrogen, or 
 b) at least one of the radicals R 1 , R 2 , A 1 , A 2 , A 3 , A 4  is different from hydrogen, or 
 c) at least one of the radicals R 1 , R 2 , B 1 , B 2 , B 3 , B 4 , B 5  is different from hydrogen, or 
 d) at least one of the radicals A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , B 5  is different from hydrogen, or 
 e) at least one of the radicals R 1 , R 2  is different from hydrogen, or 
 f) at least one of the radicals A 1 , A 2 , A 3 , A 4  is different from hydrogen, or 
 g) at least one of the radicals B 1 , B 2 , B 3 , B 4 , B 5  is different from hydrogen, or 
 h) at least two of the radicals R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , B 5  are different from hydrogen, or 
 i) at least one of the radicals R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , B 1 , B 2 , B 3 , B 4 , B 5  is F or Cl. 
 
     
     
         5 . A method of treating a parasitic infection in an animal comprising administering to the animal the pharmaceutical composition of  claim 1 . 
     
     
         6 . The method according to  claim 5 , wherein the parasitic infection is a helminth infection. 
     
     
         7 . The method according to  claim 5 , wherein the pharmaceutical composition is administered orally. 
     
     
         8 . The method according to  claim 5 , wherein the pharmaceutical composition is administered parenterally. 
     
     
         9 . A compound selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and pharmaceutically acceptable solvates, N-oxides and salts thereof. 
       
     
     
         10 . A pharmaceutical composition, wherein the composition comprises:
 a) one or more compounds as defined in  claim 9 , and   b) one or more pharmaceutically acceptable excipients, and/or one or more pharmaceutically acceptable active ingredients which differ in structure from component a).   
     
     
         11 . A method of treating a parasite infection in an animal, comprising administering to the animal a pharmaceutical composition as defined in  claim 10 . 
     
     
         12 . The method of  claim 11 , wherein the parasite infection is a helminth infection. 
     
     
         13 . The method of  claim 12 , wherein the helminth infection is a nematode infection. 
     
     
         14 . A kit, wherein the kit comprises:
 a) one or more compounds as defined in  claim 1 , and   b) one or more other components selected from the group consisting of an excipient, an active ingredient, an apparatus for combining the compound of component a) with an excipient and/or active ingredient, an apparatus for administering the compound of component a) to an animal, and a diagnostic tool.   
     
     
         15 - 16 . (canceled) 
     
     
         17 . The method as claimed in  claim 11 , wherein one or more of the parasites are resistant to one or more antiparasitic compounds. 
     
     
         18 . The method of  claim 11 , wherein the animal is a non-human mammal. 
     
     
         19 . The method of  claim 5 , wherein the animal is a non-human mammal. 
     
     
         20 . The method of  claim 5 , wherein one or more of the parasites are resistant to one or more antiparasitic compounds. 
     
     
         21 . The method of  claim 6 , wherein the helminth infection is a nematode infection. 
     
     
         22 . The method of  claim 11 , wherein the pharmaceutical composition is administered orally. 
     
     
         23 . The method of  claim 11 , wherein the pharmaceutical composition is administered parenterally.

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