US2022281825A1PendingUtilityA1

Heterocyclic compounds for the treatment of arenavirus infection

64
Assignee: ARISAN THERAPEUTICS INCPriority: Jul 12, 2016Filed: Apr 21, 2022Published: Sep 8, 2022
Est. expiryJul 12, 2036(~10 yrs left)· nominal 20-yr term from priority
A61K 31/519A61K 31/5377A61K 31/4985C07D 473/00A61K 31/4184C07D 405/04C07D 235/20A61P 31/14C07D 249/18A61K 31/454A61K 31/5025A61K 31/7105A61K 31/437C07D 487/04A61K 31/423C07D 413/00A61K 31/4192A61K 31/52A61K 45/06C07D 261/20C07D 231/56C07D 471/08C07D 235/06A61K 31/53A61K 31/4439C07D 403/14A61K 31/416A61K 31/7056A61K 31/439C07D 471/04A61K 31/713C07D 209/08C07D 403/04
64
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

The invention relates to compounds of structural formula Iwherein A, D, and E are independently N or C—R3, G, H, and J are independently N or C, K is N or C—H, L is N, N—R3 or C—R3, and A, D, E, G, H, J, K, and L together cannot have more than 4 N, R1 is selected from (C6 to C10) aryl, (C2 to C9) heteroaryl, and 5-indolyl, wherein each of the said (C6 to C10) aryl and (C2 to C9) heteroaryl is substituted with at least one R4a group, and wherein said (C2 to C9) heteroaryl is C-attached, and R2 is selected from the group consisting of

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of treating arenavirus infection comprising administration of a therapeutically effective amount of a compound of Structural Formula I 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier, diluent, or vehicle thereof, wherein:
 A, D, E, and K are independently N or C—R 3 ; 
 G, H, and J are independently N or C; 
 L is N, N—R 3 , or C—R 3 ; 
 and A, D, E, G, H, J, K, and L together cannot have more than 4 N; 
 and when G and H are C, and A, D, E, and K are C—R 3  then J and L together cannot be N; 
 R 1  is selected from (C 6  to C 10 ) aryl and (C 2  to C 9 ) heteroaryl, wherein 
 each of the said (C 6  to C 10 ) aryl and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 4  group, and wherein said (C 2  to C 9 ) heteroaryl is C-attached; 
 R 2  is selected from (C 6  to C 10 ) aryl and (C 2  to C 9 ) heteroaryl, wherein 
 each of the said (C 6  to C 10 ) aryl and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 4  group; 
 each of the R 3  is independently selected from hydrogen, halogen, cyano, OH, CF 3 , (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, —C(O)R 5 , —C(O)NR 6a R 6b , —NR 6a R 6b , —S(O) m R 5 , —S(O) m NR 6a R 6b , —NR 6a S(O) m R 5 , —(CH 2 ) n C(O)OR 5 , —(CH 2 ) n C(O)NR 6a R 6b , —OC(O)R 5 , —NR 6a C(O)R 5 , and —NR 6c C(O)NR 5a R 5b , wherein 
 each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 4  group; 
 R 4  is independently selected from hydrogen, halogen, cyano, OH, CF 3 , (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, —C(O)R 5 , —C(O)NR 6a R 6b , —NR 6a R 6b , —S(O) m R 5 , —S(O) m NR 6a R 6b , —NR 6a S(O) m R 5 , —(CH 2 ) n C(O)OR 5 , —(CH 2 ) n C(O)NR 6a R 6b , —OC(O)R 5 , —NR 6a C(O)R 5 , and —NR 6c C(O)NR 6a R 6b , wherein 
 each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 7  group; 
 each of the R 5  is independently selected from hydrogen, (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, wherein 
 each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 7  group; 
 each of the R 6 , R 6b , and R 6c  are independently selected from hydrogen, (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, 
 or R 6a  and R 6b  may be taken together with the nitrogen atom to which they are attached to form a 4 to 8 membered cycloheteroalkyl ring, wherein 
 said 4 to 8 membered cycloheteroalkyl ring has 1 to 3 ring heteroatoms selected from the group consisting of N, O, and S, and wherein 
 the said 4 to 8 membered cycloheteroalkyl ring is optionally substituted with at least one R 7  group; 
 R 7  is independently selected from hydrogen, halogen, OH, CF 3 , (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, cyano, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, —C(O)R 8 , —C(O)NR 9a R 9b , —NR 9a R 9b , —S(O) m R 8 , —S(O) m NR 9a R 9b , —NR 9a S(O) m R 8 , —(CH 2 ) n C(O)OR 8 , —(CH 2 ) n C(O)N(R 9a R 9b ), —OC(O)R 8 , —NR 9a C(O)R 8 , and —NR 9a C(O)N(R 9a R 9b ), wherein 
 each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, is optionally substituted with at least one R 10  group; 
 each of the R 8  is independently selected from hydrogen, (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, wherein 
 each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 10  group; 
 each of the R 9a , R 9b , and R 9c  are independently selected from hydrogen, (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, 
 or R 9a  and R 9b  may be taken together with the nitrogen atom to which they are attached to form a 4 to 8 membered cycloheteroalkyl ring, wherein 
 said 4 to 8 membered cycloheteroalkyl ring has 1 to 3 ring heteroatoms selected from the group consisting of N, O, and S, and wherein 
 the said 4 to 8 membered cycloheteroalkyl ring is optionally substituted; 
 R 10  is independently selected from hydrogen, halogen, cyano, OH, CF 3 , (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, wherein 
 each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted; 
 m is 0, 1, or 2; 
 n is 0, 1, 2, 3, 4, 5, or 6. 
 
     
     
         2 . The method of  claim 1 , wherein:
 R 2  is selected from the group consisting of   
       
         
           
           
               
               
           
         
       
       wherein
 R 4b  is selected from (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, —C(O)R 5 , wherein 
 each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 7  group. 
 
     
     
         3 . The method of  claim 2 , wherein:
 R 4b  is selected from the group consisting of   isopropoxy, cyclopropoxy, tert-butoxy, cyclopropylmethoxy, (2-hydroxypropan)-2-yl, (1-hydroxycyclopropan)-1-yl, (1-hydroxycyclobutan)-1-yl, difluoromethoxy, methoxyethoxy, difluoromethyl, cyclopropyl, acetyl, n-propyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, cyclobutyloxy, cyclopentyloxy, (1-hydroxycyclopentan)-1-yl, hydroxyethoxy, ethoxyethoxy, isopropoxyethoxy, isopropyl, n-propyl, n-butyl, isobutyl, sec-butyl, cyclobutyl, cyclopentyl, tert-butyl, propanoyl, isobutanoyl, sec-butanoyl, tert-butanoyl, cyclopropanoyl, cyclobutanoyl, and cyclopentanoyl.   
     
     
         4 . The method of  claim 1 , wherein:
 G and H are C;   J and L are N;   K is C—R 3 .   
     
     
         5 . The method of  claim 1 , wherein:
 G and J are C;   H and L are N;   K is C—R 3 .   
     
     
         6 . The method of  claim 5 , wherein:
 A, D, and E are C—R 3 .   
     
     
         7 . The method of  claim 1 , wherein:
 A, D, and E are independently C—R 3 ;   G and H are C;   J, K, and L are N.   
     
     
         8 . A method of treating arenavirus infection comprising administration of a therapeutically effective amount of a compound selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 8 , wherein the compound is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 2  including administrating a therapeutic amount of a therapeutic agent selected from the group consisting of Ribavirin, viral RNA-dependent-RNA-polymerase inhibitors, Triazavirin, small interfering RNAs (siRNAs) and microRNAs, vaccines, and immunomodulators. 
     
     
         11 . The method of  claim 9  including administrating a therapeutic amount of a therapeutic agent selected from the group consisting of Ribavirin, viral RNA-dependent-RNA-polymerase inhibitors, Triazavirin, small interfering RNAs (siRNAs) and microRNAs, vaccines, and immunomodulators. 
     
     
         12 . A compound of Structural Formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier, diluent, or vehicle thereof, wherein: 
         A, D, and E are independently N or C—R 3 ; 
         G, H, and J are independently N or C; 
         K is N or C—H; 
         L is N, N—R 3 , or C—R 3 ; 
         and A, D, E, G, H, J, K, and L together cannot have more than 4 N; 
         and when G and H are C, and A, D, E, and K are C—R 3  then J and L together cannot be N; 
         R 1  is selected from (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, and 5-indolyl, wherein 
         each of the said (C 6  to C 10 ) aryl and (C 2  to C 9 ) heteroaryl is substituted with at least one R 4a  group, and wherein said (C 2  to C 9 ) heteroaryl is C-attached; 
         with the proviso that R 1  is not selected from the group consisting of substituted 3-carbamoyl-2-phenyl-1-benzofuran-5-yl, substituted 1,3,4-oxadiazolyl, substituted 1,3,4-triazolyl, substituted 1,3,4-thiadiazolyl, substituted oxazoyl, substituted thiazoyl, substituted 1H-pyrazol-4-yl, substituted 1H-pyrazol-5-yl, optionally substituted 1-phenyl-1H-imidazol-5-yl, 4-{[(2-aminoethyl)amino]methyl}phenyl, (2-amino-1,3-benzoxazol)-5-yl; (2-amino-1,3-benzoxazol)-4-yl, 2-chloropyridyl-3-yl, 2-methylpyridinyl-4-yl, 2-fluoropyridyl-4-yl, 6-aminopyridyl-3-yl, 6-methoxypyridyl-3-yl, pyridyl-4-yl-N-oxide, 3,4-difluorophenyl, and substituted 1H-pyrrol-3-yl; 
         R 2  is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         each of the R 3  is independently selected from hydrogen, halogen, cyano, OH, CF 3 , (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, —C(O)R 5 , —C(O)NR 6a R 6b , —NR 6a R 6b , —S(O) m R 5 , —S(O) m NR 6a R 6b , —NR 6a S(O) m R 5 , —(CH 2 ) n C(O)OR 5 , —(CH 2 ) n C(O)NR 6a R 6b , —OC(O)R 5 , —NR 6a C(O)R 5 , and —NR 6c C(O)NR 5a R 5b , wherein 
         each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 7  group; 
         R 4a  is independently selected from halogen, cyano, OH, CF 3 , (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, —C(O)R 5 , —NR 6a R 6b , —S(O) m R 5 , —S(O) m NR 6a R 6b , —NR 6a S(O) m R 5 , —OC(O)R 5 , —NR 6a C(O)R 5 , and —NR 6c C(O)NR 6a R 6b , wherein 
         each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 7  group; 
         R 4b  is selected from the group consisting of 
         isopropoxy, cyclopropoxy, tert-butoxy, cyclopropylmethoxy, (2-hydroxypropan)-2-yl, (1-hydroxycyclopropan)-1-yl, (1-hydroxycyclobutan)-1-yl, difluoromethoxy, methoxyethoxy, difluoromethyl, cyclopropyl, acetyl, n-propyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, cyclobutyloxy, cyclopentyloxy, (1-hydroxycyclopentan)-1-yl, hydroxyethoxy, ethoxyethoxy, isopropoxyethoxy, isopropyl, n-propyl, n-butyl, sec-butyl, cyclobutyl, cyclopentyl, propanoyl, isobutanoyl, sec-butanoyl, tert-butanoyl, cyclopropanoyl, cyclobutanoyl, and cyclopentanoyl; 
         each of the R 5  is independently selected from hydrogen, (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, wherein 
         each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 7  group; 
         each of the R 6a , R 6b , and R 6c  are independently selected from hydrogen, (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, 
         or R 6a  and R 6b  may be taken together with the nitrogen atom to which they are attached to form a 4 to 8 membered cycloheteroalkyl ring, wherein 
         said 4 to 8 membered cycloheteroalkyl ring has 1 to 3 ring heteroatoms selected from the group consisting of N, O, and S, and wherein 
         the said 4 to 8 membered cycloheteroalkyl ring is optionally substituted with at least one R 7  group; 
         R 7  is independently selected from hydrogen, halogen, OH, CF 3 , (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, cyano, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, —C(O)R 8 , —C(O)NR 9a R 9b , —NR 9a R 9b , —S(O) m R 8 , —S(O) m NR 9a R 9b , —NR 9a S(O) m R 8 , —(CH 2 ) n C(O)OR 8 , —(CH 2 ) n C(O)N(R 9a R 9b ), —OC(O)R 8 , —NR 9a C(O)R 8 , and —NR 9a C(O)N(R 9a R 9b ), wherein 
         each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, is optionally substituted with at least one R 10  group; 
         each of the R 8  is independently selected from hydrogen, (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, wherein 
         each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted with at least one R 10  group; 
         each of the R 9a , R 9b , and R 9c  are independently selected from hydrogen, (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, (C 2  to C 9 ) heteroaryl, 
         or R 9a  and R 9b  may be taken together with the nitrogen atom to which they are attached to form a 4 to 8 membered cycloheteroalkyl ring, wherein 
         said 4 to 8 membered cycloheteroalkyl ring has 1 to 3 ring heteroatoms selected from the group consisting of N, O, and S, and wherein 
         the said 4 to 8 membered cycloheteroalkyl ring is optionally substituted; 
         R 10  is independently selected from hydrogen, halogen, cyano, OH, CF 3 , (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl, wherein 
         each of the said (C 1  to C 6 ) alkyl, (C 2  to C 6 ) alkenyl, (C 2  to C 6 ) alkynyl, (C 1  to C 6 ) alkoxy, aryloxy, (C 3  to C 10 ) cycloalkyl, (C 5  to C 10 ) cycloalkenyl, (C 2  to C 9 ) cycloheteroalkyl, (C 6  to C 10 ) aryl, and (C 2  to C 9 ) heteroaryl is optionally substituted; 
         m is 0, 1, or 2; 
         n is 1, 2, 3, 4, 5, or 6; 
         with the proviso that 
         the following compounds are excluded: 
       
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound of  claim 12 , wherein R 4b  is isopropoxy. 
     
     
         14 . The compound of  claim 12 , wherein:
 G and H are C;   J and L are N;   K is C—H.   
     
     
         15 . The compound of  claim 13 , wherein:
 G and H are C;   J and L are N;   K is C—H.   
     
     
         16 . The compound of  claim 14 , wherein:
 D and E are independently C—R 3 ;   A is N.   
     
     
         17 . The compound of  claim 14 , wherein:
 A and E are independently C—R 3 ;   D is N.   
     
     
         18 . The compound of  claim 14 , wherein:
 E is C—R 3 ;   A and D are N.   
     
     
         19 . The compound of  claim 12 , wherein:
 G and H are C;   J is N;   K is CH;   L is C—R 3 .   
     
     
         20 . The compound of  claim 12 , wherein:
 G and H are C;   J and K are N;   L is C—R 3 .   
     
     
         21 . The compound of  claim 12 , wherein:
 G, H, and J are C;   K and L are independently is N or N—R 3 .   
     
     
         22 . The compound of  claim 12 , wherein:
 G and J are C;   H and L are N;   K is C—H.   
     
     
         23 . The compound of  claim 13 , wherein:
 G and J are C;   H and L are N;   K is C—H.   
     
     
         24 . The compound of  claim 22 , wherein:
 A, D, and E are C—R 3 .   
     
     
         25 . The compound of  claim 23 , wherein:
 A, D, and E are independently C—R 3 .   
     
     
         26 . The compound of  claim 23 , wherein:
 A is N;   D and E are independently C—R 3 .   
     
     
         27 . The compound of  claim 23 , wherein:
 A and D are independently C—R 3 ;   E is N.   
     
     
         28 . The compound of  claim 12 , wherein:
 A, D, and E are independently C—R 3 , G and H are C;   J, K, and L are N.   
     
     
         29 . The compound of  claim 13 , wherein:
 A, D, and E are independently C—R 3 ;   G and H are C;   J, K, and L are N.   
     
     
         30 . The compound of  claim 12 , wherein:
 A, D, and E are independently C—R 3 ;   G and J are C;   H, K, and L are N.   
     
     
         31 . A compound selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         32 . The compound of  claim 31 , wherein the compound is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         33 . The compound of  claim 12 , wherein said compound is incorporated into a composition comprising a therapeutically effective amount of said compound, and a pharmaceutically acceptable carrier, diluent, or vehicle. 
     
     
         34 . The compound of  claim 32 , wherein said compound is incorporated into a composition comprising a therapeutically effective amount of said compound, and a pharmaceutically acceptable carrier, diluent, or vehicle.

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.