US2006222607A1PendingUtilityA1

Tricyclic quinoxaline and quinoline derivatives as UV filters

Assignee: PFLUCKER FRANKPriority: Mar 9, 2001Filed: Jun 5, 2006Published: Oct 5, 2006
Est. expiryMar 9, 2021(expired)· nominal 20-yr term from priority
A61K 8/4946A61P 17/16C07D 487/04A61K 8/494A61Q 17/04A61P 17/06A61K 2800/52
58
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Claims

Abstract

The invention relates to the use of quinoxaline derivatives of formula I, represented by formulas Ia and Ib, as photostable UV filters, in particular in cosmetic and pharmaceutical preparations for protecting the human epidermis or human hair against UV radiation, above all in the 280-400 nm range.

Claims

exact text as granted — not AI-modified
1 - 14 . (canceled)  
   
   
       15 . A quinoxaline compound of formula VIII  
     
       
         
         
             
             
         
       
     
     wherein 
 R, R 1  and R 2  are each, independently of one another, H, alkyl, alkoxy, alkenyl or alkynyl, each having up to 20 carbon atoms, cycloalkyl, cycloalkoxy, cycloalkenyl or bicyclic systems, each having up to 10 carbon atoms, where, in all of these groups, one or more hydrogen atoms may also be substituted by Sub 1  and/or one or two CH 2  groups may be replaced by C═O, and the cyclic systems may contain 1 to 3 heteroatoms, Hal, OH, NO 2 , —(CR 5 R 6 ) n —NR 5 R 6 —(CR 5 R 6 ) n —N═CR 5 R 6 , —(CR 5 R 6 ) n —CR 5 ═NR 5 , —(CR 5 R 6 ) n —NHCOR 5 , —(CR 5 R 6 ) n —NHCOOR 5 , —SR 5 , —SO 2 —R 5 , NR 5 —SO—R 6 , —SO—R 5 , water-solubilising substituents, carboxylate, sulfonate or ammonium radicals, COR 5 , COOR 5 , CON 5 R 6 , CN, O═S(—R 5 )═O, O═S(—OR 5 )═O, O═S(—NR 5 R 6 )═O, R 5 OP(—OR 6 )═O, OAr, —(CR 5 R 6 ) n —Ar, —Si(alkyl) 3 , —Si(alkyl) 2 H, -Het, —NHHet, —OHet or —(CR 5 R 6 ) n -Het,  
 R 1  and R 2  together, with carbon atoms to which they are bonded, may jointly form an unsaturated, partially or fully saturated 4-, 5-, 6- or 7-membered ring, which optionally contains one or more heteroatoms, may be further fused and/or may also be monosubstituted or polysubstituted,  
 R 4  is H or a branched or unbranched C1-20-alkyl radical, in which optionally one or more H atoms may be replaced by Sub,  
 Sub is Hal, hydroxyl, cyano, amino, nitro, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy, COR 5 , COOR 5 , OAr, OHet, —(CR 5 R 6 ) n —Ar or —(CR 5 R 6 ) n —Het, —(CR 5 R 6 ) n —NR 5 R 6 , CONR 5 R 6 , CN, O═S(—R 5 )═O, O═S(—OR 5 )═O, O═S(—NR 5 R 6 )═O or R 5 OP(—OR 6 )═O,  
 Sub 1  is Hal, hydroxyl, cyano, amino, nitro, C 1 -C 4 -alkylamino, C 1 -C 4 -dialkylamino, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy, COOH or COO-alkyl,  
 Hal is fluorine, chlorine, bromine or iodine,  
 n is 0, 1, 2, 3 or 4,  
 m is 1, 2 or 3,  
 R 5  and R 6  are each, independently of one another, H, alkyl, alkenyl, alkynyl, each having up to 20 carbon atoms, cycloalkyl, cycloalkenyl, bicyclic systems, each having up to 10 carbon atoms, where these radicals may be up to trisubstituted by Sub 1  and/or one or two CH 2  groups may be replaced by C═O, and the cyclic systems may also contain 1 to 3 heteroatoms, —(CR′R″) n —Ar or —(CR′R″) n —Het, or the radicals R 5  and R 6  may also, with one another, in each case together with carbon atoms to which they are bonded, jointly form an unsaturated, partially or fully saturated 4-, 5-, 6- or 7-membered ring, which optionally contains one or more heteroatoms, may also be monosubstituted or polysubstituted and/or may be further fused,  
 R′ and R″ are each, independently of one another, H or C 1 -C 4 -alkyl, in which one or two CH 2  groups may also be replaced by C═O,  
 Ar is an unsubstituted or monosubstituted or polysubstituted aromatic ring or fused ring systems having 6 to 18 carbon atoms, in which one or two CH groups may also be replaced by C═O, and  
 Het is an unsubstituted or monosubstituted or polysubstituted heteroaromatic ring having 5 to 7 ring members or a fused ring system, where the heteroatoms present are one or more N, S and/or O atoms, and in which one or two CH groups in the α- or β-position to the heteroatoms may also be replaced by C═O.  
 
   
   
       16 . A compound according to  claim 15 , wherein R 4  is H, methyl, ethyl or ethyl or ethylhexyl.  
   
   
       17 . A compound according to  claim 15 , wherein R is a branched or unbranched C 1-20 -alkyl radical, in which, optionally one or more H atoms are replaced by Sub.  
   
   
       18 . A compound according to  claim 17 , wherein Sub is methyl, ethyl, isopropyl or tertiary-butyl.  
   
   
       19 . A compound according to  claim 15 , which is 1-(2-ethylhexyl)-2-phenylimidazo[3,4-b]quinoxaline.  
   
   
       20 . A compound according to  claim 15 , wherein the phenyl ring of formula VII is substituted in accordance with one of the patterns shown below  
     
       
         
               
               
               
               
             
                   
               
                   
               
                   
                   
                   
                   
               
                 R 
                 m 
                 Position 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 CH 3   
                 1-3 
                 o/ m/ p; m/ m/ p; o/p; m/ m 
                   
               
                 C 2 H 5   
                 1-3 
                 ″ 
               
                 C 3 H 7   
                 1-3 
                 ″ 
               
                   n C 4 H 9   
                 1-3 
                 ″ 
               
                   t C 4 H 9   
                 1-3 
                 ″ 
               
                   i C 4 H 9   
                 1-3 
                 ″ 
               
                 C 5 H 11   
                 1-3 
                 ″ 
               
                 C 18 H 37   
                 1-3 
                 ″ 
               
                 (2′-Etyl)-hexyl- 
                 1-3 
                 ″ 
               
                 OCH 3   
                 1-3 
                 o/ m/ p; m/ m/ p; o/p; m/ m 
               
                 OC 2 H 5   
                 1-3 
                 ″ 
               
                 OC 3 H 7   
                 1-3 
                 ″ 
               
                 OC 4 H 9   
                 1-3 
                 ″ 
               
                 OC 5 H 11   
                 1-3 
                 ″ 
               
                 OC 18 H 37   
                 1-3 
                 ″ 
               
                 OCOCH 3   
                 1-2 
                 o; m; p; o/p 
               
                 OCOC 2 H 5   
                 1-2 
                 ″ 
               
                 OCOC 3 H 7   
                 1-2 
                 ″ 
               
                 OCOC 4 H 9   
                 1-2 
                 ″ 
               
                 OCOC 5 H 11   
                 1-2 
                 ″ 
               
                 OCOC 18 H 37   
                 1-2 
                 ″ 
               
                 OH 
                 1-3 
                 o/ m/ p; m/ m/ p; o/p; m/ m 
               
                 F 
                 1-2 
                 o; p; o/p 
               
                 Cl 
                 1-2 
                 o; p; o/p 
               
                 CF 3   
                 1 
                 o; m; p 
               
                 NO 2   
                 1-3 
                 m/; m/ m; o/ o/ p 
               
                 NHCOR 5   
                 1 
                 P 
               
                 NHCOOR 5   
                 1 
                 P 
               
                 COR 5   
                 1-2 
                 o; p; o/p 
               
                 COOR 5   
                 1-2 
                 o; p; o/p 
               
                 CONR 5 R 6   
                 1-2 
                 o; p; o/p 
               
                 CN 
                 1 
                 P 
               
                 O═S(OR 5 )═O 
                 1 
                 P 
               
                 O═S(R 5 )═O 
                 1 
                 P 
               
                 O═S(NR 5 R 6 )═O 
                 1 P 
               
                 R 5 OP(—OR 6 )═O 
                 1 
                 P 
               
                   
               
                   
               
           
              
              
              
              
              
             
             
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
             
          
         
       
     
   
   
       21 . A compound according to  claim 15 , wherein R is CH 3 ; C 2 H 5 ; C 3 H 7 ;  n C 4 H 9 ;  1 C 4 H 9 ;  i C 4 H 9 ; C 5 H 11 ; C 18 H 37 ; (2′-Etyl)-hexyl-; OCH 3 ; OC 2 H 5 ; OC 3 H 7 ; OC 4 H 9 ; OC 5 H 11 ; OC 18 H 37 ; OCOCH 3 ; OCOC 2 H 5 ; OCOC 3 H 7 ; OCOC 4 H 9 ; OCOC 5 H 11 ; OCOC 18 H 37 ; OH; F; Cl; CF 3 ; NO 2 ; NHCOR 5 ; NHCOOR 5 ; COR 5 ; COOR 5 ; CONR 5 R 6 ; CN; O═S(OR 5 )═O; O═S(R 5 )═O; O═S(NR 5 R 6 )═O; or R 5 OP(—OR 6 )═O.  
   
   
       22 . A cosmetic or pharmaceutical composition comprising a compound of  claim 15  and a pharmaceutically or cosmetically acceptable excipient.  
   
   
       23 . A cosmetic or pharmaceutical composition comprising an effective amount of a compound of  claim 15  alone or together with a UV-absorbent compound suitable for protection of the human epidermis or human hair against UV light in the range of 280 to 400 nm together with one or more pharmaceutically or cosmetically acceptable excipients.  
   
   
       24 . A cosmetic or pharmaceutical composition comprising a compound of  claim 20  and a pharmaceutically or cosmetically acceptable excipient.  
   
   
       25 . A cosmetic or pharmaceutical composition comprising an effective amount of a compound of  claim 20  alone or together with a UV-absorbent compound suitable for protection of the human epidermis or human hair against UV light in the range of 280 to 400 nm together with one or more pharmaceutically or cosmetically acceptable excipients.  
   
   
       26 . A process for the preparing a compound of formula VII according to  claim 15  comprising reacting 2,3-dichloroquinoxaline, which is substituted by R 1  and R 2  corresponding to the target compound of formula VII, to form a compound of formula VII.  
   
   
       27 . A process according to  claim 26 , wherein one of the chlorine atoms of the 2,3-dichloroquinoxaline is replaced by an amino function and the other chlorine atom is replaced by —NH—R 4 .  
   
   
       28 . A process according to  claim 27  further comprising reacting the obtained quinoxaline with a suitably substituted benzaldehyde compound to obtain a compound of formula VII.  
   
   
       29 . A method for protecting skin and/or hair of a human from ultraviolet radiation comprising applying onto said skin and/or hair an effective amount of a compound of formula VIII according to  claim 15 .  
   
   
       30 . A method according to  claim 29 , wherein 
 R 4  is H, methyl, ethyl or ethyl or ethylhexyl,    R is a branched or unbranched C 1-20 -alkyl radical, in which, optionally one or more H atoms are replaced by methyl, ethyl, isopropyl or tertiary-butyl.    
   
   
       31 . A method according to  claim 29 , wherein 
 R 4  is H, methyl, ethyl or ethyl or ethylhexyl,    R is a branched or unbranched C 1-20 -alkyl radical, in which, two or three H atoms are replaced by methyl, ethyl, isopropyl or tertiary-butyl.    
   
   
       32 . A method for protecting skin and/or hair of a human from ultraviolet radiation comprising applying onto said skin and/or hair an effective amount of a compound of formula VIII according to  claim 20 .  
   
   
       33 . A compound according to  claim 15 , wherein m is 2 or 3, and R is alkyl, alkoxy, alkenyl or alkynyl, each having up to 20 carbon atoms, cycloalkyl, cycloalkoxy, cycloalkenyl or bicyclic systems, each having up to 10 carbon atoms, where, in all of these groups, one or more hydrogen atoms may also be substituted by Sub 1  and/or one or two CH 2  groups may be replaced by C═O, and the cyclic systems may contain 1 to 3 heteroatoms, Hal, OH, NO 2 , —(CR 5 R 6 ) n —NR 5 R 6 , —(CR 5 R 6 ) n —N═CR 5 R 6 , —(CR 5 R 6 )—CR 5 ═NR 5 , —(CR 5 R 6 ) n —NHCOR 5 , —(CR 5 R 6 ) n —NHCOOR 5 , —SR 5 , —SO 2 —R 5 , NR 5 —SO—R 6 , —SO—R 5 , water-solubilising substituents, carboxylate, sulfonate or ammonium radicals, COR 5 , COOR 5 , CON 5 R 6 , CN, O═S(—R 5 )═O, O═S(—OR 5 )═O, O═S(—NR 5 R 6 )═O, R 5 OP(—OR 6 )═O, OAr, —(CR 5 R 6 ) n —Ar, —Si(alkyl) 3 , —Si(alkyl) 2 H, -Het, —NHHet, —OHet or —(CR 5 R 6 )n-Het.  
   
   
       34 . A compound according to  claim 21 , wherein m is 2 or 3.

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