Aminobenzoic acid derivatives for use as anti-inflammatory agents, anti-metastatic agents and/or anticancer agents

Abstract

in which R2, R2, R3, R4 and Q can represent various different possibilities. These compounds can be useful as anticancer agents as well as anti-inflammatory agents, anti-proliferative agents and/or anti-metastatic agents.

1 - 13 . (canceled) 
     
     
         14 . A compound of formula (IIA), (IIB) or (IIC): 
       
         
           
           
               
               
           
         
         wherein 
         Q is Q A  or Q B ; 
       
       
         
           
           
               
               
           
         
         R 2  is H, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         R 5  is H, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         R 6  is H, Boc, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         R 7  is a substituted or unsubstituted member chosen from C 1 -C 8  alkyl, C 3 -C 8  cycloalkyl, phenyl, furanyl, thiophenyl, pyridinyl, naphthyl, quinolyl and isoquinolyl; 
         R 9  is H or C 1 -C 8  alkyl; 
         X is O, S or NR 2 , 
         n is 1, 2 or 3; 
         wherein R 2 , R 5 , R 6  and R 7 , when substituted, are substituted with at least one substituent chosen from —OR 9 , —F, —Cl, —Br, —I, acetyl, propiolyl, butyryl, isobutyryl, benzoyl, —NO 2 , C 1 -C 8  alkyl, methoxycarbonyl-, or alkyloxycarbonyl-; 
       
       or an enantiomer, diastereoisomer, racemic mixture, pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         15 - 38 . (canceled) 
     
     
         39 . The method of  claim 57 , wherein said cancer cell growth is inhibited by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% relative to an untreated subject. 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 57 , wherein a relative STAT1 activation of said cells is decreased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% relative to untreated cancer cells. 
     
     
         42 . The method of  claim 57 , or wherein a relative STAT3 activation of said cells is decreased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% relative to untreated cancer cells. 
     
     
         43 . The method of  claim 57 , wherein a CD40 expression of said cells is decreased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% relative to untreated cancer cells. 
     
     
         44 . The method of  claim 57 , wherein a MHC-II expression of said cells is decreased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% relative to untreated cancer cells. 
     
     
         45 . The method of  claim 57 , wherein a production of NO of said cells is decreased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% relative to untreated cancer cells. 
     
     
         46 . The method of  claim 57 , wherein TNFα/NFκB and/or IL6/STAT3 signaling pathways of said cells is decreased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% relative to untreated cells. 
     
     
         47 . The method of  claim 57 , wherein an LPS-activated NFκB signaling pathway of said cells is decreased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70% or about 80% relative to untreated cells. 
     
     
         48 - 55 . (canceled) 
     
     
         56 . A method for treating cancer or at least one cancer chosen from melanoma, breast cancer, uterine cancer, ovarian cancer, prostate cancer and bladder cancer, said method comprising administering to a subject in need thereof an effective amount of at least one compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, alkyl or halogen; 
         R 2  is H, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         Q is Q A  or Q B ; 
       
       
         
           
           
               
               
           
         
           =a single bond or a double bond; 
         R 5  is H, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         R 6  is H, Boc, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         R 7  is a substituted or unsubstituted member chosen from C 1 -C 8  alkyl, C 3 -C 8  cycloalkyl, phenyl, furanyl, thiophenyl, pyridinyl, naphthyl, quinolyl and isoquinolyl; 
         R 3  and R 4  are independently chosen from H, —SR 8  and —NR 9 R 10 , 
         or R 3  and R 4  are joined together to form a 5-7 membered ring that optionally comprises an heteroatom chosen from N, S and O; 
         R 8  is H, C 1 -C 8  alkyl, —(CH 2 ) n NHBoc, or —(CH 2 ) n NH 2  wherein n=1 to 6; 
         R 9  is H or C 1 -C 8  alkyl; 
         R 10  is H, C 1 -C 8  alkyl, acetyl, propiolyl, butyryl, isobutyryl, or benzoyl; 
         wherein R 2 , R 5 , R 6  and R 7 , when substituted, are substituted with at least one substituent chosen from —OR 9 , —F, —Cl, —Br, —I, acetyl, propiolyl, butyryl, isobutyryl, benzoyl, —NO 2 , C 1 -C 8  alkyl, methoxycarbonyl-, or alkyloxycarbonyl-; 
       
       or an enantiomer, diastereoisomer, racemic mixture, pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         57 . A method for inhibiting cancer cell growth, the cancer chosen from melanoma, breast cancer, uterine cancer, ovarian cancer, prostate cancer and bladder cancer, said method comprising administering to a subject in need thereof an effective amount of at least one compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, alkyl or halogen; 
         R 2  is H, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         Q is Q A  or Q B ; 
       
       
         
           
           
               
               
           
         
           =a single bond or a double bond; 
         R 5  is H, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         R 6  is H, Boc, or a substituted or unsubstituted member chosen from acetyl, propiolyl, butyryl, isobutyryl and benzoyl; 
         R 7  is a substituted or unsubstituted member chosen from C 1 -C 8  alkyl, C 3 -C 8  cycloalkyl, phenyl, furanyl, thiophenyl, pyridinyl, naphthyl, quinolyl and isoquinolyl; 
         R 3  and R 4  are independently chosen from H, —SR 8  and —NR 9 R 10 , 
         or R 3  and R 4  are joined together to form a 5-7 membered ring that optionally comprises an heteroatom chosen from N, S and O; 
         R 8  is H, C 1 -C 8  alkyl, —(CH 2 ) n NHBoc, or —(CH 2 ) n NH 2  wherein n=1 to 6; 
         R 9  is H or C 1 -C 8  alkyl; 
         R 10  is H, C 1 -C 8  alkyl, acetyl, propiolyl, butyryl, isobutyryl, or benzoyl; 
         wherein R 2 , R 5 , R 6  and R 7 , when substituted, are substituted with at least one substituent chosen from —OR 9 , —F, —Cl, —Br, —I, acetyl, propiolyl, butyryl, isobutyryl, benzoyl, —NO 2 , C 1 -C 8  alkyl, methoxycarbonyl-, or alkyloxycarbonyl-; 
       
       or an enantiomer, diastereoisomer, racemic mixture, pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         58 - 59 . (canceled) 
     
     
         60 . The method of  claim 57 , wherein said compound is a compound of formula (IA): 
       
         
           
           
               
               
           
         
       
       wherein R 2 , R 3 , R 4  and Q are as defined in any one of claims  52  to  55 . 
     
     
         61 . The method of  claim 57 , wherein
 R 2  is H, unsubstituted member chosen from acetyl and propiolyl;   Q is Q A ;   R 5  is H, unsubstituted member chosen from acetyl and propiolyl; and   R 6  is Boc, H, or an unsubstituted member chosen from acetyl and propiolyl.   
     
     
         62 . The method of  claim 57 , wherein said compound is a compound of formula (IB): 
       
         
           
           
               
               
           
         
       
       wherein R 2 , R 3 , R 4  and Q are as defined in claim  1 . 
     
     
         63 . The method of  claim 57 , wherein
 R 2  is H, unsubstituted member chosen from acetyl and propiolyl;   Q is Q A ;   R 5  is H, unsubstituted member chosen from acetyl and propiolyl; and   R 6  is Boc, H, or an unsubstituted member chosen from acetyl and propiolyl.   
     
     
         64 . The method of  claim 57 , wherein said compound is a compound of formula (IC): 
       
         
           
           
               
               
           
         
       
       wherein R 2 , R 5  and R 6  are as defined in claim  1 . 
     
     
         65 . The method of  claim 57 , wherein
 R 2  is H, unsubstituted member chosen from acetyl and propiolyl;   Q is Q A ;   R 5  is H, unsubstituted member chosen from acetyl and propiolyl; and   R 6  is Boc, H, or an unsubstituted member chosen from acetyl and propiolyl.   
     
     
         66 . The method of  claim 57 , wherein said compound is a compound of formula (ID): 
       
         
           
           
               
               
           
         
       
       wherein R 2 , R 3 , R 4  and R 7  are as defined in claim  1 . 
     
     
         67 . The method of  claim 57 , wherein
 R 2  is H or unsubstituted member chosen from acetyl and propiolyl; and   R 7  is an unsubstituted member chosen from C 1 -C 8  alkyl, C 3 -C 6  cycloalkyl, phenyl, furanyl, thiophenyl, pyridinyl, naphthyl, quinolyl and isoquinolyl.   
     
     
         68 . The method of  claim 57 , wherein said compound is a compound of formula (IE): 
       
         
           
           
               
               
           
         
       
       wherein R 2  and R 7  are as defined in claim  1 . 
     
     
         69 . The method of  claim 57 , wherein
 R 2  is H or an unsubstituted member chosen from acetyl and propiolyl; and   R 7  is an unsubstituted member chosen from C 1 -C 8  alkyl, C 3 -C 6  cycloalkyl, phenyl, furanyl, thiophenyl, pyridinyl, naphthyl, quinolyl and isoquinolyl.   
     
     
         70 . The method of  claim 57 , wherein said compound is chosen from: 
       
         
           
           
               
               
           
         
       
     
     
         71 . The method of  claim 57 , wherein said compound is chosen from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         72 . The method of  claim 57 , wherein said compound is chosen from