C-Pyrazole A2A Receptor Agonists

Abstract

2-adenosine C-pyrazole compounds having formula (a) and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.

1 . A compound of matter having the formula: 
       
         
           
           
               
               
           
         
       
       wherein R 1  is —CH 2 OH, —C(═O)NR 5 R 6 ;
 R 2  is selected from the group consisting of hydrogen, C 1-15  alkyl, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and heteroaryl substituents are optionally substituted with from 1 to 3 substituents independently selected from the group consisting of halo, NO 2 , heterocyclyl, aryl, heteroaryl, CF 3 , CN, OR 20 , SR 20 , N(R 20 )2, S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , SO 2 NR 20 COR 22 , SO 2 NR 20 C0 2 R 22 , SO 2 NR 20 CON(R 20 ) 2 , N(R 20 ) 2 , NR 20 COR 22 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , NR 20 C(NR 20 )NHR 23 , COR 20 , CO2R 20 , CON(R 20 ) 2 , and OCON(R 20 ) 2  and wherein each optional heteroaryl, aryl, and heterocyclyl substituent is optionally substituted with halo, NO 2 , alkyl, CF 3 , amino, mono- or di-alkylamino, alkyl or aryl or heteroaryl amide, NCOR 22 , NR 20 SO 2 R 22 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 CON(R 20 ), OC(O)N(R 20 ) 2 ; SR 20 , S(O)R 22 , SO2R 22 , SO 2 N(R 20 ) 2 , CN, and OR 20 ; 
 R 3 , R 4  are each individually selected from the group consisting of hydrogen, C 1-15 , alkyl, C 2-15 , alkenyl, C 2-15 , alkynyl, heterocyclyl, aryl, and heteroaryl, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R20) 2 , SO 2 NR 20 COR 22 , SO 2 NR 20 R 22 , SO 2 NR 20 CON(R 20 ) 2 , N(R 20 ) 2  NR 20 COR 22 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , NR 20 C(NR 20 )NHR 23 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , CONR 20 SO 2 R 22 , NR 20 SO 2 R 22 , SO 2 NR 20 CO 2 R 22 , OCONR 20 SO 2 R 22 , OC(O)R 20 , C(O)OCH 2 OC(O)R 20 , and OCON(R 20 ) 2 , wherein the alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and heteroaryl substituents are optionally substituted with from 1 to 3 substituents independently selected from the group consisting of halo, NO 2 , heterocyclyl, aryl, heteroaryl, CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , SO 2 NR 20 COR 22 , SO 2 NR 20 CO 2 R 22 , SO 2 NR 20 CON(R 20 ) 2 , N(R 20 ) 2  NR 20 COR 22 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , SO 2 NR 20 CO 2 R 22 , OCONR 20 SO 2 R 22 , OC(O)R 20 , C(O)OCH 2 OC(O)R 20 , and OCON(R 20 ) 2 , and wherein each optional heteroaryl, aryl, and heterocyclyl substituent is optionally substituted with halo, NO 2 , alkyl, CF 3 , amino, mono- or di-alkylamino, alkyl or aryl or heteroaryl amide, NCOR 22 , NR 20 SO 2 R 22 , COR 20 , CO2R 20 , CON(R 20 ) 2 , NR 20 CON(R 20 ) 2 , OC(O)R 20 , OC(O)N(R 20 ) 2 , SR 20 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , CN, AND OR 20 ; 
 R 5  and R 6  are each individually selected from H, C 1-15 , alkyl with from 1 to 2 substituents independently selected from the group consisting of halo, NO 2 , heterocyclyl, aryl, heteroaryl, CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 )2, SO 2 NR 20 COR 22 , SO 2 NR 20 CO 2 R 22 , SO 2 NR 20 CON(R 20 ) 2 , N(R 20 ) 2 , NR 20 COR 22 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , NR 20 C(NR 20 )NHR 23 , COR 2 O, CO 2 R 20 , CON(R 20 ) 2 , CONR 20 SO 2 R 22 , NR 20 SO 2 R 22 , SO 2 NR 20 CO 2 R 22 , OCONR 20 SO 2 R 22 , OC(O)R 20 , C(O)OCH 2 OC(O)R 20 , and OCON(R 20 ) 2 , and wherein each optional heteroaryl, aryl, and heterocyclyl substituent is optionally substituted with halo, NO 2 , alkyl, CF 3 , amino, mono- or di-alkylamino, alkyl or aryl or heteroaryl amide, NCOR 22 , NR 20 SO2R 22 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 CON(R 20 ) 2 , OC(O)R 20 , OC( )N(R 20 ) 2 , SR 20 , S( )R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , CN, AND OR 20 ; 
 R 20  is selected from the group consisting of H, C 1-15 , alkyl, C 2-15  alkenyl, alkynyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, heterocyclyl, aryl, and heteroaryl substituents are optionally substituted with from 1 to 3 substituents independently selected from halo, alkyl, mono- or dialkylamino; alkyl or aryl or heteroaryl amide, CN, O—C 1-6 , alkyl, CF 3 , aryl, and heteroaryl; and 
 R 22  is a member selected from the group consisting of C 1-15 , alkyl, C 2-15 , alkenyl, alkynyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, heterocyclyl, aryl, and heteroaryl substituents are optionally substituted with from 1 to 3 substituents independently selected from halo, alkyl, mono- or dialkylamino, alkyl or aryl or heteroaryl amide, CN, O—C 1-16 , alkyl, CF 3 , and heteroaryl wherein, when R 1  is CH 2 OH, and R 3  is H and R 4  is H, and the pyrazole ring is attached through C 4 , then R, is not H. 
 
     
     
         2 .- 34 . (canceled)