Thioxanthene derivatives for the treatment of infectious diseases

Abstract

The claimed subject matter is directed to certain thioxanthene derivatives and phenothiazine derivatives suitable for use as anti-infective agents, in particular, for the treatment of infectious diseases. The claimed subject matter furthermore relates to compositions including said anti-infective agents.

1 .- 15 . (canceled) 
     
     
         16 . A compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 V is selected from the group consisting of S, SO 2 , SO, O, and NH; 
 W is C═CH—(CHX) n —CX(R 9 )(R 10 ), or W is C═CH—(CHX) n-1 —CH═C(R 9 )(R 10 ); 
 n is an integer in the range of from 1 to 5; 
 each X is hydrogen; 
 R 1 , R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are each independently selected from the group consisting of hydrogen, halogen, hydroxy, amino, nitro, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkoxy, C 2-6 -alkenyloxy, carboxy, C 1-6 -alkoxycarbonyl, C 1-6 -alkylcarbonyl, fomyl, C 1-6 -alkylsulphonylamino, aryl, aryloxycarbonyl, aryloxy, arylcarbonyl, arylamino, arylsulphonylamino, heteroaryl, heteroaryloxycarbonyl, heteroaryloxy, heteroarylcarbonyl, heteroarylamino, heteroarylsulphonylamino, heterocyclyl, heterocyclyloxycarbonyl, heterocyclyloxy, heterocyclylcarbonyl, heterocyclylamino, heterocyclylsulphonylamino, mono- and di(C 1-6 -alkyl)amino, carbamoyl, mono- and di(C 1-6 -alkyl)aminocarbonyl, amino-C 1-6 -alkyl-aminocarbonyl, mono- and di(C 1-6 -alkyl)amino-C 1-6 -alkyl-aminocarbonyl, C 1-6 -alkylcarbonylamino, amino-C 1-6 -alkylcarbonylamino, mono- and di(C 1-6 -alkyl)amino-C 1-6 -alkyl-carbonylamino, amino-C 1-6 -alkyl-amino, mono- and di(C 1-6 -alkyl)amino-C 1-6 -alkyl-amino, cyano, guanidino, carbamido, C 1-6 -alkanoyloxy, C 1-6 -alkylsulphonyl, C 1-6 -alkylsulphinyl, C 1-6 -alkylsulphonyloxy, aminosulfonyl, mono- and di(C 1-6 -alkyl)aminosulfonyl, and C 1-6 -alkylthio; 
 R 2  is selected from the group consisting of F, Cl, Br, I, CH 2 Y, CHY 2 , and CY 3 , wherein Y is a halogen atom; and 
 R 9  and R 10  together with the carbon atom to which they are attached form an optionally substituted C 3-6 -cycloalkyl or C 3-6 -heterocyclyl; or 
 a salt thereof. 
 
     
     
         17 . The compound according to  claim 16 , wherein R 9  and R 10  together with the carbon atom to which they are attached form a nitrogen-containing heterocyclyl. 
     
     
         18 . The compound according to  claim 16 , wherein V is S. 
     
     
         19 . The compound according to  claim 16 , wherein n is 2, 3, or 4. 
     
     
         20 . The compound according to  claim 16 , wherein R 9  and R 10  together with the carbon atom to which they are attached form an piperazinyl or piperidinyl. 
     
     
         21 . The compound according to  claim 20 , wherein R 9  and R 10  together with the carbon atom to which they are attached form an piperidinyl. 
     
     
         22 . The compound according to  claim 16 , wherein R 9  and R 10  together with the carbon atom to which they are attached form an nitrogen-containing heteroaryl or heterocyclyl wherein the nitrogen atom is separated by two carbon atoms from the carbon atom to which R 9  and R 10  are attached. 
     
     
         23 . The compound according to  claim 16  of formula (II) 
       
         
           
           
               
               
           
         
       
       wherein;
 V is selected from the group consisting of S, SO 2 , SO, O, and NH; 
 W′ is C═CH; 
 n is an integer in the range of from 1 to 6; 
 each X is hydrogen; 
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 14  and R 15  are each independently selected from the group consisting of hydrogen, halogen, hydroxy, amino, nitro, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkoxy, C 2-6 -alkenyloxy, carboxy, C 1-6 -alkoxycarbonyl, C 1-6 -alkylcarbonyl, fomyl, C 1-6 -alkylsulphonylamino, aryl, aryloxycarbonyl, aryloxy, arylcarbonyl, arylamino, arylsulphonylamino, heteroaryl, heteroaryloxycarbonyl, heteroaryloxy, heteroarylcarbonyl, heteroarylamino, heteroarylsulphonylamino, heterocyclyl, heterocyclyloxycarbonyl, heterocyclyloxy, heterocyclylcarbonyl, heterocyclylamino, heterocyclylsulphonylamino, mono- and di(C 1-6 -alkyl)amino, carbamoyl, mono- and di(C 1-6 -alkyl)aminocarbonyl, amino-C 1-6 -alkyl-aminocarbonyl, mono- and di(C 1-6 -alkyl)amino-C 1-6 -alkyl-aminocarbonyl, C 1-6 -alkylcarbonylamino, amino-C 1-6 -alkyl-carbonylamino, mono- and di(C 1-6 -alkyl)amino-C 1-6 -alkyl-carbonylamino, amino-C 1-6 -alkyl-amino, mono- and di(C 1-6 -alkyl)amino-C 1-6 -alkyl-amino, cyano, guanidino, carbamido, C 1-6 -alkanoyloxy, C 1-6 -alkylsulphonyl, C 1-6 -alkylsulphinyl, C 1-6 -alkylsulphonyloxy, aminosulfonyl, mono- and di(C 1-6 -alkyl)aminosulfonyl, and C 1-6 -alkylthio; and 
 R 13  is hydrogen, halogen, hydroxy, amino, nitro, C 1-6 -alkyl, or C 1-6 -alkoxy; or 
 a salt thereof. 
 
     
     
         24 . A pharmaceutical composition for the treatment of a bacterial infection, comprising the compound of  claim 16  and an additional anti-infective agent. 
     
     
         25 . A method for treating a bacterial infection in a subject, comprising:
 administering to the subject a therapeutically effective amount of the compound of  claim 16 .   
     
     
         26 . A pharmaceutical composition comprising the compound of  claim 16 , and at least one pharmaceutically acceptable carrier or excipient. 
     
     
         27 . The pharmaceutical composition of  claim 26 , further comprising at least one additional anti-infective agent. 
     
     
         28 . A method for treating a bacterial infection in a subject, comprising:
 administering to the subject a therapeutically effective amount of the compound of  claim 16 .