Aryl-or heteroaryl-substituted benzene compounds

Abstract

The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

1 .- 30 . (canceled) 
     
     
         31 . A compound of Formula (Ig), or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R 2  is methyl; 
         R 4  is methyl; 
         R 6  is phenyl substituted with one or more -Q 2 -T 2 , wherein Q 2  is C 1 -C 3  alkyl linker optionally substituted with halo or hydroxyl, and wherein T 2  is —NRaRb, in which each of Ra and Rb, independently is H or C 1 -C 6  alkyl, or Ra and Rb, together with the N atom to which they are attached, form a 4 to 12-membered heterocycloalkyl ring having 0 or 1 additional heteroatom, the C 1 -C 6  alkyl and the 4 to 12-membered heterocycloalkyl ring being optionally substituted with one or more -Q 3 -T 3 ; wherein Q 3  is a bond or C 1 -C 3  alkyl linker each optionally substituted with halo, cyano, hydroxyl or C 1 -C 6  alkoxy, and T 3  is selected from the group consisting of halo, cyano, C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 12-membered heterocycloalkyl, 5- or 6-membered heteroaryl, OR d , COOR d , —S(O) 2 R d , NR d R e , and —C(O)NR d R e , each of R d  and R e  independently being H or C 1 -C 6  alkyl; 
         R 7  is C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl or 4 to 7-membered heterocycloalkyl, each optionally substituted with one or more -Q 5 -T 5 , wherein Q 5  is a bond, C(O), C(O)NR k , NR k C(O), S(O) 2 , or C 1 -C 3  alkyl linker, R k  being H or C 1 -C 6  alkyl, and T 5  is H, halo, C 1 -C 6  alkyl, hydroxyl, cyano, C 1 -C 6  alkoxyl, amino, mono- C 1 -C 6  alkylamino, di- C 1 -C 6  alkylamino, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, 5- or 6-membered heteroaryl, or S(O) q R q  in which q is 0, 1, or 2 and R q  is C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and T 5  is optionally substituted with one or more substituents selected from the group consisting of halo, C 1 -C 6  alkyl, hydroxyl, cyano, C 1 -C 6  alkoxyl, amino, mono- C 1 -C 6  alkylamino, di- C 1 -C 6  alkylamino, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, 5- or 6-membered heteroaryl, except when T 5  is H, halo, hydroxyl, or cyano; 
         R 8  is ethyl; and 
         R 12  is methyl. 
       
     
     
         32 . The compound of  claim 31 , or a pharmaceutically acceptable salt thereof, wherein Ra and Rb, together with the N atom to which they are attached, form a 4 to 12-membered heterocycloalkyl ring having 0 or 1 additional heteroatom, the 4 to 12-membered heterocycloalkyl ring being optionally substituted with one or more -Q 3 -T 3 . 
     
     
         33 . The compound of  claim 31 , or a pharmaceutically acceptable salt thereof, wherein R 7  is C 3 -C 8  cycloalkyl optionally substituted with one or more -Q 5 -T 5 . 
     
     
         34 . The compound of  claim 31  or a pharmaceutically acceptable salt thereof, wherein R 7  is 4 to 7-membered heterocycloalkyl, each optionally substituted with one or more -Q 5 -T 5 . 
     
     
         35 . The compound of  claim 31 , or a pharmaceutically acceptable salt thereof, wherein R 7  is piperidinyl, tetrahydropyran, cyclopentyl, or cyclohexyl, each optionally substituted with one or more -Q 5 -T 5 . 
     
     
         36 . A compound of Formula (II), or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein 
         Q 2  is C 1 -C 3  alkyl linker optionally substituted with halo or hydroxyl, and wherein T 2  is —NR aRb, in which each of Ra and Rb, independently is H or C 1 -C 6  alkyl, or Ra and Rb, together with the N atom to which they are attached, form a 4 to 12-membered heterocycloalkyl ring having 0 or 1 additional heteroatom, the C 1 -C 6  alkyl and the 4 to 12-membered heterocycloalkyl ring being optionally substituted with one or more -Q 3 -T 3 ; wherein Q 3  is a bond or C 1 -C 3  alkyl linker each optionally substituted with halo, cyano, hydroxyl or C 1 -C 6  alkoxy, and T 3  is selected from the group consisting of halo, cyano, C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 12-membered heterocycloalkyl, 5- or 6-membered heteroaryl, OR a , COOR a , —S(O) 2 R d , NR d R e , and —C(O)NR d R e , each of R d  and R e  independently being H or C 1 -C 6  alkyl; 
         R 7  is C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl or 4 to 7-membered heterocycloalkyl, each optionally substituted with one or more -Q 5 -T 5 , wherein Q 5  is a bond, C(O), C(O)NR k , NR k C(O), S(O) 2 , or C 1 -C 3  alkyl linker, R k  being H or C 1 -C 6  alkyl, and T 5  is H, halo, C 1 -C 6  alkyl, hydroxyl, cyano, C 1 -C 6  alkoxyl, amino, mono- C 1 -C 6  alkylamino, di- C 1 -C 6  alkylamino, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, 5- or 6-membered heteroaryl, or S(O) q R q  in which q is 0, 1, or 2 and R q  is C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and T 5  is optionally substituted with one or more substituents selected from the group consisting of halo, C 1 -C 6  alkyl, hydroxyl, cyano, C 1 -C 6  alkoxyl, amino, mono- C 1 -C 6  alkylamino, di- C 1 -C 6  alkylamino, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, 5- or 6-membered heteroaryl, except when T 5  is H, halo, hydroxyl, or cyano; and 
         R 8  is ethyl. 
       
     
     
         37 . The compound of  claim 36 , or a pharmaceutically acceptable salt thereof, wherein R 7  is C 3 -C 8  cycloalkyl optionally substituted with one or more -Q 5 -T 5 . 
     
     
         38 . The compound of  claim 36 , or a pharmaceutically acceptable salt thereof, wherein R 7  is 4 to 7-membered heterocycloalkyl, each optionally substituted with one or more -Q 5 -T 5 . 
     
     
         39 . The compound of  claim 36 , or a pharmaceutically acceptable salt thereof, wherein R 7  is piperidinyl, tetrahydropyran, cyclopentyl, or cyclohexyl, each optionally substituted with one or more -Q 5 -T 5 . 
     
     
         40 . A compound of Formula (IIa), or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R 7  is C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl or 4 to 7-membered heterocycloalkyl, each optionally substituted with one or more -Q 5 -T 5 , wherein Q 5  is a bond, C(O), C(O)NR k , NR k C(O), S(O) 2 , or C 1 -C 3  alkyl linker, R k  being H or C 1 -C 6  alkyl, and T 5  is H, halo, C 1 -C 6  alkyl, hydroxyl, cyano, C 1 -C 6  alkoxyl, amino, mono- C 1 -C 6  alkylamino, di- C 1 -C 6  alkylamino, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, 5- or 6-membered heteroaryl, or S(O) q R q  in which q is 0, 1, or 2 and R q  is C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, or 5- or 6-membered heteroaryl, and T 5  is optionally substituted with one or more substituents selected from the group consisting of halo, C 1 -C 6  alkyl, hydroxyl, cyano, C 1 -C 6  alkoxyl, amino, mono- C 1 -C 6  alkylamino, di- C 1 -C 6  alkylamino, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 7-membered heterocycloalkyl, 5- or 6-membered heteroaryl, except when T 5  is H, halo, hydroxyl, or cyano; 
         R 8  is ethyl; and 
         Ra and Rb, together with the N atom to which they are attached, form a 4 to 12-membered heterocycloalkyl ring having 0 or 1 additional heteroatom, the 4 to 12-membered heterocycloalkyl ring being optionally substituted with one or more -Q 3 -T 3 ; wherein Q 3  is a bond or C 1 -C 3  alkyl linker each optionally substituted with halo, cyano, hydroxyl or C 1 -C 6  alkoxy, and T 3  is selected from the group consisting of halo, cyano, C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl, C 6 -C 10  aryl, 4 to 12-membered heterocycloalkyl, 5- or 6-membered heteroaryl, OR a , COOR a , —S(O) 2 R a , NR d R e , and —C(O)NR d R e , each of R d  and R e  independently being H or C 1 -C 6  alkyl. 
       
     
     
         41 . The compound of  claim 40 , or a pharmaceutically acceptable salt thereof, wherein Ra and Rb, together with the N atom to which they are attached, form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatom. 
     
     
         42 . The compound of  claim 40 , or a pharmaceutically acceptable salt thereof, wherein R 7  is C 3 -C 8  cycloalkyl optionally substituted with one or more -Q 5 -T 5 . 
     
     
         43 . The compound of  claim 40 , or a pharmaceutically acceptable salt thereof, wherein R 7  is 4 to 7-membered heterocycloalkyl, each optionally substituted with one or more -Q 5 -T 5 . 
     
     
         44 . The compound of  claim 40 , or a pharmaceutically acceptable salt thereof, wherein R 7  is piperidinyl, tetrahydropyran, cyclopentyl, or cyclohexyl, each optionally substituted with one or more -Q 5 -T 5 . 
     
     
         45 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 31  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 
     
     
         46 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 36  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 
     
     
         47 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 40  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 
     
     
         48 . A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 31  or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from lymphoma and sarcoma. 
     
     
         49 . A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 36  or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from lymphoma and sarcoma. 
     
     
         50 . A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of  claim 40  or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from lymphoma and sarcoma.