Novel 4-cyano, 4-amino and 4-aminomethyl of pyrazolo 1,5-a pyridines, pyrazolo 1,5-c pyrimidines and 2h-indazol and derivatives 5-cyano, 5-amino 5-aminomethyl and imidazo 1,2-a pyridines and imidazo 1,5-a pyrazines as inhibitors of cyclin dependent kinase.

摘要

A compound represented by the structural formula: or a pharmaceutically acceptable salt or solvate thereof, wherein: X is C or N; Y is selected from the group consisting of CN, NH2, and CH2NH2; R 1 is selected from the group consisting of H, halogen, R9, NH2, CN, alkyl, alkenyl, alkynyl, aryl, heteroaryl, CF3, heterciclilalquilo, arylalkyl, heteroarylalkyl, heterociclilalquilalquilo, cicloalqulo, cycloalkylalkyl, C (O) OR 4, alkyl substituted with 1 to 6 groups R 9 which may be the same or different and are independently selected from the list of R 9 shown below, and wherein the aryl in the definitions indicated above for R 1 can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, CN, NH2, -OR 5, SR 5, -CH 2 oR 5, -C (O) R 5, -SO3H, -S (O2) R 6, -S (O 2) NR 5 R 6, - NR 5 R 6, -C (O) NR 5 R 6, -CF 3 and -OCF 3; R 2 is selected from the group consisting of H, halogen, -NR 5 R 6, - C (O) OR 4, -C (O) NR 5 R 6, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, wherein each of said moieties of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl for R 2 and heterocyclyl, whose structures are shown immediately above for R 2, can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, selected each moiety being independently from the group consisting of halogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, CF3, CN, -OCF3, - (CR 4 R 5) n OR 6, - OR 5, -R 5 OR 5, -NR 5 R 6, - (CR 4 R 5) nNR 5 R 6, -C (O2) R 5, -C (O) R 5, -C (O) NR 6 R 6, -SR 6, -S (O 2) R 6, -S (O 2) NR 5 R 6, -N (R 5) S (O2) R7, -N (R 5) C (O) R 7 and - N (R 5) C (O) NR 5 R 6; R3 is selected from the group consisting of amino, C alkylamino, arylalkylamino, heteroarylamino, heteroarylalkylamino, hydroxyalkylamino, heterocycloalkylalkylamino, wherein each of said amino, alkylamino, cycloalkylamino, arylalkylamino, heteroarylamino, heteroarylalkylamino, hydroxyalkylamino, and heterocycloalkylalkylamino can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, selected each moiety being independently from the group consisting of halogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, heteroarylalkyl, heterocycloalkyl-alkyl, cycloalkyl, CF3 , OCF3, CN, -OR 5, -NR 5 R 6, -C (R 4 R 5) n OR 5, -C (O2) R 5, -C (O) R 5, -C (O) NR 5 R 6, -SR 6, -S (O 2) R 7, -S (O 2) NR 5 R 6, -N (R 5) S (O2) R 7, - N (R 5) C (O) R 7 and -N (R 5) C (O) NR 5 R 6; R 4 is H, halogen, CN or alkyl; R 5 is H or alkyl; R 6 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocycloalkyl, heteroaryl and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocycloalkyl, heteroaryl and heteroarylalkyl can be without unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, -OR 5, -NR 5 R 10, - N (R6) Boc, - (CR 4 R 5) n OR 5, -C (O2) R 5, - C (O) R 5, -C (O) NR 5 R 10, -SO3H, - SR 10, - S (O2) R 7, -S (O 2) NR 5 R 10, -N (R 5) S (O2) R7, -N (R5) C (O) R 7 and - N (R 5) C ( O) NR 5 R 10; R 10 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocycloalkyl, heteroaryl and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocycloalkyl, heteroaryl and heteroarylalkyl, which may be unsubstituted or optionally substituted with one or more moieties which can be the same or different, selected each other from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, -OR 5, - NR 4 R 5, - N (R 5) Boc, - (CR 4 R 5) n OR 5, -C (O2) R 5, -C (O) NR 4 R 5, -C (O) R 5, SO 3 H, -SR 5, - S (O2) R7, -S (O2) NR 4 R 5, -N (R 5) S (O2) R 7, -N (R 5) C (O) R 7 and - N (R 5) C (O) NR 4 R 5; optionally (i) R 5 and R 10 in the moiety -NR 5 R 10, or (ii) R 5 and R 6 in the moiety -NR 5 R 6 can be joined to form a cycloalkyl or heterocycloalkyl, each of said cycloalkyl or heterocycloalkyl is unsubstituted or optionally independently substituted with one or more groups R 9; R 7 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, -OR 5, -NR 5 R 10, - CH2OR 5, -C (O2) R 5, -C (O) NR 5 R 10, -C (O) R 5, -SR 10, -S (O 2) R 10, - S (O2 ) NR 5 R 10, -N (R 5) S (O2) R 10, -N (R 5) C (O) R 10 and -N (R 5) C (O) NR 5 R 10; R 8 is selected from the group consisting of R 6, -C (O) NR 5 R 10, - CH2OR 4, -C (O) OR 6, -C (O2) R 7 and S (O2) R 7; R 9 is selected from the group consisting of halogen, -CN, -NR 5 R 6, - (CH 2) n 4 - (CO2) R 6, -C (O) NR 5 R 6, -OR 6, - SR 6, -S (O 2) R 7, -S (O 2) NR 5 R 6, -N (R 5) S (O2) R 7, -N (R 5) C (O) R 7 and -N ( R 5) C (O) NR 5 R 6; m is 0 to 4; n is 1 to 4, in which, unless otherwise, each of the aryl, heteroaryl, cycloalkyl and heterocyclyl in the definitions indicated above may be optionally substituted by one or more system substituents indicated ring are identical or different, each being independently selected from the group consisting of aryl, heteroaryl, aralkyl, alkylaryl, heteroaralkyl, alkylheteroaryl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, aralkoxy, acyl, aroyl, halo, nitro, cyano, carboxyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, cycloalkyl, heterocyclyl, Y1Y2N-, Y1Y2N-alkyl-, Y1Y2NC (O) - and Y1Y2NSO2-, wherein Y1 and Y2 are same or different and are independently selected from the group consisting of hydrogen, alkyl, aryl and aralkyl.