Benzimidazolones and analogues

Abstract

The present invention provides compounds and pharmaceutical formulations useful as progesterone receptor agonists and antagonists and having the general formula: wherein: A is O, S, or NR 4 ; B is a bond or CR 5 R 6 ; R 4 , R 5 , and R 6 are H, C 1 to C 6 alkyl, C 2 to C 6 alkenyl, C 2 to C 6 alkynyl, C 3 to C 8 cycloalkyl, C 3 to C 8 cycloalkyl, aryl, or heterocyclic ring, or R 4 and R 5 form a 5 to 7 membered ring; R 1 is H, OH, NH 2 , C 1 to C 6 alkyl, C 3 to C 6 alkenyl, alkynyl, or COR A ; R 2 is H, halogen, CN, NO 2 , C 1 to C 6 alkyl, C 1 to C 6 alkoxy, or C 1 to C 6 aminoalkyl; R 3 is a substituted benzene ring or heterocyclic ring; Q is O, S, NR 8 , or CR 9 R 10 ; or a pharmaceutically acceptable salt thereof The invention also includes methods of contraception and methods of treating or preventing maladies associated with the progesterone receptor.

What is claimed:  
     
         1 . A compound of the formula:  
       
         
           
           
               
               
           
         
         wherein: 
 A is O, S, or NR 4 ;  
 B is CR 5 R 6 ;  
 R 4 , R 5 , and R 6  are independently selected from the group consisting of H, C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 2  to C 6  alkenyl, substituted C 2  to C 6  alkenyl, C 2  to C 6  alkynyl, substituted C 2  to C 6  alkynyl, C 3  to C 8  cycloalkyl, substituted C 3  to C 8  cycloalkyl, aryl, substituted aryl, heterocyclic, and substituted heterocyclic;  
 or R 4  and R 5  are fused to form a 5 to 7 membered ring;  
 R 1  is selected from the group consisting of H, OH, NH 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 6  alkenyl, substituted C 3  to C 6  alkenyl, alkynyl, substituted alkynyl, and COR A ;  
 R A  is selected from the group consisting of H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, and substituted C 1  to C 3  aminoalkyl;  
 R 2  is selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 1 to C   6  alkoxy, substituted C 1  to C 6  alkoxy, C 1  to C 6  aminoalkyl, and substituted C 1  to C 6  aminoalkyl;  
 R 3  is selected from the group consisting of a) and b): 
 a) a substituted benzene ring having the substituents X, Y and Z as shown below:  
                     X is selected from the group consisting of halogen, CN, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  thioalkoxy, substituted C 1  to C 3  thioalkoxy, C 1  to C 3  aminoalkyl, substituted C 1  to C 3  aminoalkyl, NO 2 , C 1  to C 3  perfluoroalkyl, 5 or 6 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, COR B , OCOR B , and NR C COR B ;    R B  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;    R C  is H, C 1  to C 3  alkyl or substituted C 1  to C 3  alkyl;    Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkoxy, C 1  to C 3  alkyl, and C 1  to C 3  thioalkoxy; and    
 b) a five or six membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO 2  and NR 7  and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ; 
 R D  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;  
 R E  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;  
 R 7  is H or C 1  to C 3  alkyl;  
 
 
 Q is O, S, NR 8 , or CR 9 R 10 ;  
 R 8  is selected from the group consisting of CN, C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 8  cycloalkyl, substituted C 3  to C 8  cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, and SO 2 CF 3 ;  
 R 9  and R 10  are independent substituents selected from the group consisting of H, C 1 to C   6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 8  cycloalkyl, substituted C 3  to C 8  cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO 2 , CN, and CO 2 R 11 ;  
 R 11  is C 1  to C 3  alkyl;  
 or CR 9 R 10  comprises a six membered ring of the structure:  
                     
 
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         2 . The compound according to  claim 1 , wherein: 
 R 1  is H, OH, NH 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, or COR A ;    R A  is H, C 1  to C 3  alkyl, or C 1  to C 3  alkoxy;    R 2  is H, halogen, NO 2 , C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;    R 3  is the substituted benzene ring having the substituents X and Y as shown below:                           wherein: 
 X is selected from the group consisting of halogen, CN, C 1  to C 3  alkoxy, C 1  to C 3  alkyl, NO 2 , C 1  to C 3  perfluoroalkyl, 5 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, and C 1  to C 3  thioalkoxy;  
 Y is on the 4′ or 5′ position and is selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkoxy, C 1  to C 3  alkyl, and C 1  to C 3  thioalkoxy.  
   
     
     
         3 . The compound according to  claim 1 , wherein: 
 R 3  is the five membered ring of the structure:                           wherein: 
 U is O, S, or NR 7 ;  
 R 7  is H or C 1  to C 3  alkyl;  
 X′ is selected from the group consisting of halogen, CN, NO 2 , C 1  to C 3  alkyl, and C 1  to C 3  alkoxy;  
 Y′ is H or C 1  to C 3  alkyl.  
   
     
     
         4 . The compound according to  claim 1 , wherein: 
 R 3  is the six membered ring of the structure:                           wherein: 
 X 1  is N or CX 2 ;  
 X 2  is halogen, CN or NO 2 .  
   
     
     
         5 . The compound according to  claim 24 , which is 6-(3-Nitro-phenyl)-3H-benzooxazol-2-one or a pharmaceutically acceptable salt thereof.  
     
     
         6 . The compound according to  claim 24 , which is 6-(3-Nitro-phenyl)-3H-benzothiazol-2-one or a pharmaceutically acceptable salt thereof.  
     
     
         7 . The compound according to  claim 24 , which is 6-(3-Chloro-phenyl)-3H-benzothiazol-2-one or a pharmaceutically acceptable salt thereof.  
     
     
         8 . The compound according to  claim 1 , which is 7-(3-Nitro-phenyl)-4H-benzo[1,4]thiazin-3-one or a pharmaceutically acceptable salt thereof.  
     
     
         9 . The compound according to  claim 1 , which is 2-Ethyl-7-(3-nitro-phenyl)-4H-benzo[1,4]thiazin-3-one or a pharmaceutically acceptable salt thereof.  
     
     
         10 . The compound according to  claim 1 , which is 8-(3-Chloro-phenyl-1,2,3,3a-tetrahydro-5H-pyrrolo[1,2-a]quinoxalin-4-one or a pharmaceutically acceptable salt thereof.  
     
     
         11 . The compound according to  claim 1 , which is 6-(3-Chloro-phenyl)-4-methyl-3,4-dihydro-1H-quinoxalin-2-one or a pharmaceutically acceptable salt thereof.  
     
     
         12 . The compound according to  claim 1 , which is 5-(3,4-Dihydro-4-methyl-2-oxo-quinoxalin-6-yl) thiophene-3-carbonitrile or a pharmaceutically acceptable salt thereof.  
     
     
         13 . The compound according to  claim 1 , which is 4-(n-Butyl)-6-(3-chloro-phenyl)-3,4-dihydro-1H quinoxalin-2-one or a pharmaceutically acceptable salt thereof.  
     
     
         14 . The compound according to  claim 1 , which is 6-(3-Cyano-5-fluorophenyl)-4-isopropyl-3,4-dihydro-1H-quinoxalin-2-one or a pharmaceutically acceptable salt thereof.  
     
     
         15 . The compound according to  claim 1 , which is 6-(3-Chloro-4-fluoro-phenyl)-4-isopropyl-3,4-dihydro-1H-quinoxalin-2-one or a pharmaceutically acceptable salt thereof.  
     
     
         16 . The compound according to  claim 1 , which is 6-(3-Chloro-phenyl)-4-isopropyl-3,4-dihydro-1H-quinoxalin-2-one or a pharmaceutically acceptable salt thereof.  
     
     
         17 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient.  
     
     
         18 . The pharmaceutical composition according to  claim 17  wherein Q is O.  
     
     
         19 . The pharmaceutical composition according to  claim 17  wherein Q is S, NR 7 , or CR 8 R 9 .  
     
     
         20 . A method of inducing contraception in a mammal, the method comprising administering to a mammal in need thereof a compound of  claim 1 , or a pharmaceutically acceptable salt thereof.  
     
     
         21 . A method of treatment or prevention of benign or malignant neoplastic disease in a mammal, the method comprising administering to a mammal in need thereof a compound of  claim 1 , or a pharmaceutically acceptable salt thereof.  
     
     
         22 . The method according to  claim 21  wherein the benign or malignant neoplastic disease is selected from the group consisting of uterine myometrial fibroids, endometriosis, benign prostatic hypertrophy; carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, pituitary, meningioma and other hormone-dependent tumors.  
     
     
         23 . A method of treatment in a mammal of carcinomas or adenocarcinomas of the endometrium, ovary, breast, colon, or prostate, the method comprising administering to a mammal in need thereof a compound of  claim 1 , or a pharmaceutically acceptable salt thereof.  
     
     
         24 . A compound of the formula:  
       
         
           
           
               
               
           
         
         wherein: 
 A is O or S;  
 B is a bond between A and C═Q;  
 R 1  is selected from the group consisting of H, OH, NH 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 6  alkenyl, substituted C 3  to C 6  alkenyl, alkynyl, substituted alkynyl, and COR A ;  
 R A  is selected from the group consisting of H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, and substituted C 1  to C 3  aminoalkyl;  
 R 2  is selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 1 to C   6  alkoxy, substituted C 1  to C 6  alkoxy, C 1  to C 6  aminoalkyl, and substituted C 1  to C 6  aminoalkyl;  
 R 3  is selected from the group consisting of a), b), c), and d): 
 a) a substituted benzene ring having the substituents X, Y and Z as shown below:  
                     X is selected from the group consisting of halogen, CN, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  thioalkoxy, substituted C 1  to C 3  thioalkoxy, C 1  to C 3  aminoalkyl, substituted C 1  to C 3  aminoalkyl, NO 2 , C 1  to C 3  perfluoroalkyl, 5 or 6 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, COR B , OCOR B , and NR C COR B ;    R B  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;    R C  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;    Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkoxy, C 1  to C 3  alkyl, and C 1  to C 3  thioalkoxy;    
 b) a five membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO 2  and NR 7  and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ;  
 c) a six membered ring having in its backbone 2 or 3 NR 7  heteroatoms and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ; and  
 d) a six membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, and SO 2  and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ; 
 R D  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;  
 R E  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;  
 R 7  is H or C 1  to C 3  alkyl;  
 Q is O;  
 
 
 
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         25 . A compound of the formula:  
       
         
           
           
               
               
           
         
         wherein: 
 A is S;  
 B is a bond between A and C═Q;  
 R 1  is selected from the group consisting of H, OH, NH 2 , C 1  to C 6 alkyl, substituted C 1  to C 6  alkyl, C 3  to C 6  alkenyl, substituted C 3  to C 6  alkenyl, alkynyl, substituted alkynyl, and COR A ;  
 R A  is selected from the group consisting of H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, and substituted C 1  to C 3  aminoalkyl;  
 R 2  is selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 1  to C 6  alkoxy, substituted C 1  to C 6  alkoxy, C 1  to C 6  aminoalkyl, and substituted C 1  to C 6  aminoalkyl;  
 R 3  is selected from the group consisting of a), b), c), and d): 
 a) a substituted benzene ring having the substituents X, Y and Z as shown below:  
                     X is selected from the group consisting of halogen, CN, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  thioalkoxy, substituted C 1  to C 3  thioalkoxy, C 1  to C 3  aminoalkyl, substituted C 1  to C 3  aminoalkyl, NO 2 , C 1  to C 3  perfluoroalkyl, 5 or 6 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, COR B , OCOR B , and NR C COR B ;    R B  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;    R C  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;    Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkoxy, and C 1  to C 3  thioalkoxy;    
 b) a five membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of S, SO, SO 2  and NR 7  and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkoxy, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ;  
 c) a five membered ring having in its backbone 2 or 3 O heteroatoms and having one or two independent substituents selected from the group consisting of halogen, CN, NO 2 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ; and  
 d) a six membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO 2  and NR 7  and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ; 
 R D  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;  
 R E  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;  
 R 7  is H or C 1  to C 3  alkyl;  
 Q is CR 9 R 10 ;  
 R 9  and R 10  are independent substituents selected from the group consisting of H, C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 8  cycloalkyl, substituted C 3  to C 8  cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO 2 , CN, and CO 2 R 11 ;  
 R 11  is C 1  to C 3  alkyl,  
 or CR 9 R 10  comprises a six membered ring of the structure:  
                     
 
 
 
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         26 . A compound of the formula:  
       
         
           
           
               
               
           
         
         wherein: 
 A is O;  
 B is a bond between A and C═Q;  
 R 1  is selected from the group consisting of H, OH, NH 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 6  alkenyl, substituted C 3  to C 6  alkenyl, alkynyl, substituted alkynyl, and COR A ;  
 R A  is selected from the group consisting of H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, and substituted C 1  to C 3  aminoalkyl;  
 R 2  is selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 1  to C 6  alkoxy, substituted C 1  to C 6  alkoxy, C 1 to C   6  aminoalkyl, and substituted C 1  to C 6  aminoalkyl;  
 R 3  is selected from the group consisting of a) and b): 
 a) a substituted benzene ring having the substituents X, Y and Z as shown below:  
                     X is selected from the group consisting of halogen, CN, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  thioalkoxy, substituted C 1  to C 3  thioalkoxy, C 1  to C 3  aminoalkyl, substituted C 1  to C 3  aminoalkyl, NO 2 , C 1  to C 3  perfluoroalkyl, 5 or 6 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, COR B , OCOR B , and NR C COR B ;    R B  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;    R C  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;    Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkyl, to C 3  alkoxy, and C to C 3  thioalkoxy; and    
 b) a five or six membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO 2  and NR 7  and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ; 
 R D  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;  
 R E  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;  
 R 7  is H or C 1  to C 3  alkyl;  
 
 
 Q is CR 9 R 10 ;  
 R 9  and R 10  are independent substituents selected from the group consisting of H, C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 8  cycloalkyl, substituted C 3  to C 8  cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO 2 , CN, and CO 2 R 11 ;  
 R 11  is C 1  to C 3  alkyl, or CR 9 R 10  comprises a six membered ring of the structure:  
                     
 
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         27 . A compound of the formula:  
       
         
           
           
               
               
           
         
         wherein: 
 A is O or S;  
 B is a bond between A and C═Q;  
 R 1  is selected from the group consisting of H, OH, NH 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 6  alkenyl, substituted C 3  to C 6  alkenyl, alkynyl, substituted alkynyl, and COR A ;  
 R A  is selected from the group consisting of H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, and substituted C 1  to C 3  aminoalkyl;  
 R 2  is selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 1  to C 6  alkoxy, substituted C 1 to C   6  alkoxy, C 1  to C 6  aminoalkyl, and substituted C 1  to C 6  aminoalkyl;  
 R 3  is selected from the group consisting of a), b), c), and d): 
 a) a substituted benzene ring having the substituents X, Y and Z as shown below:  
                     X is selected from the group consisting of halogen, CN, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  thioalkoxy, substituted C 1  to C 3  thioalkoxy, C 1  to C 3  aminoalkyl, substituted C 1  to C 3  aminoalkyl, NO 2 , C 1  to C 3  perfluoroalkyl, 5 or 6 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, COR B , OCOR B , and NR C COR B ;    R B  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;    R C  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;    Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkoxy, C 1  to C 3  alkyl, and C 1  to C 3  thioalkoxy; and    
 b) a five or six membered ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, SO, SO 2  and NR 7  and having one or two independent substituents selected from the group consisting of H, halogen, CN, NO 2 , C 1  to C 3  alkyl, C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, COR D , and NR E COR D ; 
 R D  is H, C 1  to C 3  alkyl, substituted C 1  to C 3  alkyl, aryl, substituted aryl, C 1  to C 3  alkoxy, substituted C 1  to C 3  alkoxy, C 1  to C 3  aminoalkyl, or substituted C 1  to C 3  aminoalkyl;  
 R E  is H, C 1  to C 3  alkyl, or substituted C 1  to C 3  alkyl;  
 R 7  is H or C 1  to C 3  alkyl;  
 
 
 Q is S or NR 8 ;  
 R 8  is selected from the group consisting of CN, C 1  to C 6  alkyl, substituted C 1  to C 6  alkyl, C 3  to C 8  cycloalkyl, substituted C 3  to C 8  cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, and SO 2 CF 3 ;  
 
         or a pharmaceutically acceptable salt thereof.