| 主权项 |
1. A method of treating a subject suffering from an ALK-, FAK- or JAK2-mediated disorder or condition comprising administering to the subject a therapeutically effective amount of a compound of Formula I wherein: A is H, cyano, F, Cl, Br, CH3 or CF3; R1 is H, heterocyclyl, heteroaryl, carbocyclyl, aryl, C1-6alkyl, C1-6alkoxy, carbocyclyloxy, or C1-6alkylamino, where, when R1 is a nitrogen containing heterocyclyl, the nitrogen may be substituted with C1-6alkyl, hydroxy(C2-3)alkyl, dihydroxy (C3)alkyl, C1-6alkoxy(C2-3)alkyl, aminocarbonyl(C1-3)alkyl, N—(C1-6)alkylaminocarbonyl(C1-3)alkyl, N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl, where the (C1-6)alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl may be the same or different, (C1-6alkyl)sulfonyl(C2-3)alkyl, (C1-6 alkyl)sulfonyl, amino(C2-3)alkylcarbonyl, N—(C1-6alkyl)amino(C2-3)alkylcarbonyl, N,N-(di-C1-6alkyl)amino(C2-3)alkylcarbonyl, where the alkyl groups of N,N-di-(C1-6alkyl)amino(C2-3)alkylcarbonyl may be the same or different, heteroaryl or heterocyclyl, and where, when R1 is heterocyclyl, heteroaryl, carbocyclyl, or aryl, such heterocyclyl, heteroaryl, carbocyclyl, or aryl may be unsubstituted, or substituted with one or two substituents independently selected from the group consisting of C1-6alkyl, hydroxyl, hydroxy(C1-3)alkyl, C1-6alkoxy, C1-6alkoxy(C1-3)alkyl, aminocarbonyl(C1-3)alkyl, N—(C1-6)alkylaminocarbonyl(C1-3)alkyl, N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl, where the (C1-6)alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl may be the same or different, (C1-6alkyl)sulfonyl(C1-3)alkyl, amino, (C1-6)alkylamino, di-(C1-6)alkylamino, where the alkyl groups of di-(C1-6)alkylamino may be the same or different, (C1-6)alkylsulfonyl, fluorine, carboxy, amino(C1-3)alkylcarbonyl, N—(C1-6alkyl)amino(C1-3)alkylcarbonyl, N,N-(di-C1-6alkyl)amino(C1-3)alkylcarbonyl, where the alkyl groups of N,N-(di-C1-6alkyl)amino(C1-3)alkylcarbonyl may be the same or different, and heterocyclyl, and where, when R1 is C1-6alkyl, C1-6alkoxy, or C1-6alkylamino, the alkyl groups of such C1-6alkyl, C1-6alkoxy, or C1-6alkylamino may be unsubstituted, or substituted with one, two or three substituents independently selected from the group consisting of heterocyclyl, heteroaryl, hydroxyl, amino, (C1-6)alkylamino, di-(C1-6)alkylamino, where the alkyl groups of di-(C1-6)alkylamino may be the same or different, carboxy, aminocarbonyl,N—(C1-6)alkylaminocarbonyl, N,N-di-(C1-6)alkylaminocarbonyl, where the alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl may be the same or different, aminosulfonyl, and C1-6alkylsulfonyl;
R2 is H, heterocyclyl, heteroaryl, carbocyclyl, aryl, C1-6alkyl, C1-6alkoxy, or C1-6alkylamino, where, when R2 is a nitrogen containing heterocyclyl, the nitrogen may be substituted with H, C1-6alkyl, hydroxy(C2-3)alkyl, dihydroxy (C3)alkyl, C1-6alkoxy(C2-3)alkyl, aminocarbonyl(C1-3)alkyl, N—(C1-6)alkylaminocarbonyl(C1-3)alkyl, N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl, where the (C1-6)alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl may be the same or different, (C1-6alkyl)sulfonyl(C2-3)alkyl, (C1-6 alkyl)sulfonyl, amino(C2-3)alkylcarbonyl, N—(C1-6alkyl)amino(C2-3)alkylcarbonyl, N,N-(di-C1-6alkyl)amino(C2-3)alkylcarbonyl, where the alkyl groups of N,N-(di-C1-6alkyl)amino(C2-3)alkylcarbonyl may be the same or different, heteroaryl or heterocyclyl, and where, when R2 is heterocyclyl, heteroaryl, carbocyclyl, or aryl, such heterocyclyl, heteroaryl, carbocyclyl, or aryl may be unsubstituted, or substituted with one or two substituents independently selected from the group consisting of C1-6alkyl, hydroxyl, hydroxy(C1-3)alkyl, C1-6alkoxy, C1-6alkoxy(C1-3)alkyl, aminocarbonyl(C1-3)alkyl, N—(C1-6)alkylaminocarbonyl(C1-3)alkyl, N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl, where the (C1-6)alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl may be the same or different, (C1-6alkyl)sulfonyl(C1-3)alkyl, amino, (C1-6)alkylamino, di-(C1-6)alkylamino, where the alkyl groups of di-(C1-6)alkylamino may be the same or different, (C1-6)alkylsulfonyl, fluoro, carboxy, amino(C1-3)alkylcarbonyl, N—(C1-6alkyl)amino(C1-3)alkylcarbonyl, N,N-(di-C1-6alkyl)amino(C1-3)alkylcarbonyl, where the alkyl groups of N,N-(di-C1-6alkyl)amino(C1-3)alkylcarbonyl may be the same or different, and heterocyclyl, and where, when R2 is C1-6alkyl, C1-6alkoxy, or C1-6alkylamino, the alkyl groups of such C1-6alkyl, C1-6alkoxy, or C1-6alkylamino may be unsubstituted, or substituted with one, two or three substituents independently selected from the group consisting of heterocyclyl, heteroaryl, hydroxyl, amino, (C1-6)alkylamino, di-(C1-6)alkylamino, where the alkyl groups of di-(C1-6)alkylamino may be the same or different, carboxy, aminocarbonyl,N—(C1-6)alkylaminocarbonyl, N,N-di-(C1-6)alkylaminocarbonyl, where the alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl may be the same or different, aminosulfonyl, and C1-6alkylsulfonyl; or
R1 and R2, together with the phenyl ring to which they are attached, form a five- to eight-membered monocarbocyclic or monoheterocyclic ring, where the ring so formed by R1 and R2, may be unsubstituted, or substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, amino(C1-3)alkyl, N—(C1-6alkyl)amino(C1-3)alkyl, N,N-di-(C1-6alkyl)amino(C1-3)alkyl, where the alkyl groups of N,N-di-(C1-6alkyl)amino(C1-3)alkyl may be the same or different, alkoxy(C1-6)alkyl, hydroxyl, hydroxy(C1-6)alkyl, (C1-6alkyl)sulfonyl(C1-3)alkyl, heterocyclyl, amino, (C1-6)alkylamino, di-(C1-6)alkylamino, where the alkyl groups of di-(C1-6)alkylamino may be the same or different, carboxy, aminocarbonyl, N—(C1-6)alkylaminocarbonyl, N,N-di-(C1-6)alkylaminocarbonyl, where the alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl may be the same or different, aminocarbonyl(C1-3)alkyl, N—(C1-6)alkylaminocarbonyl(C1-3)alkyl, N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl, where the (C1-6)alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl may be the same or different, and aminosulfonyl; R3 is H, C1-6alkoxy, or Cl; where at least one of R1 and R3 is other than H; R4 and R5, independently, are H, C1-6alkoxy, aminocarbonyl, N—(C1-6alkyl)aminocarbonyl, N,N-di-(C1-6alkyl)aminocarbonyl, where the alkyl groups of N,N-di-(C1-6alkyl)aminocarbonyl may be the same or different, (C1-6alkyl)sulfonyl, aminosulfonyl, N—(C1-6alkyl)aminosulfonyl, N,N-di-(C1-6alkyl)aminosulfonyl, where the alkyl groups of N,N-di-(C1-6alkyl)aminosulfonyl may be the same or different, N—[(C1-6alkyl)sulfonyl]amino, N—[(C1-6alkyl)sulfonyl]-N—(C1-6alkyl)amino, where the alkyl groups of N—[(C1-6alkyl)sulfonyl]-N—(C1-6alkyl)amino may be the same or different, (C1-6alkyl)2phosphinyl, where the alkyl groups of (C1-6alkyl)2phosphinyl may be the same or different, or heteroaryl, where, when R4 or R5 is heteroaryl, such heteroaryl may be unsubstituted, or substituted with one or two substituents independently selected from the group consisting of C1-6alkyl, hydroxyl, hydroxy(C1-3)alkyl, C1-6alkoxy, C1-6alkoxy(C1-3)alkyl, aminocarbonyl(C1-3)alkyl, N—(C1-6)alkylaminocarbonyl(C1-3)alkyl, N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl, where the (C1-6)alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl may be the same or different, (C1-6alkyl)sulfonyl(C1-3)alkyl, amino, (C1-6)alkylamino, di-(C1-6)alkylamino, where the alkyl groups of di-(C1-6)alkylamino may be the same or different, (C1-6alkyl)sulfonyl, fluorine, carboxy, aminocarbonyl, N—(C1-6)alkylaminocarbonyl, and N,N-di-(C1-6)alkylaminocarbonyl, where the alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl may be the same or different, and where, when R4 or R5 is N—(C1-6alkyl)aminocarbonyl or C1-6alkoxy, the alkyl groups of such N—(C1-6alkyl)aminocarbonyl or C1-6alkoxy may be unsubstituted, or substituted by one, two or three substituents independently selected from the group consisting of heterocyclyl, hydroxyl, amino, (C1-6)alkylamino, di-(C1-6)alkylamino, where the alkyl groups of di-(C1-6)alkylamino may be the same or different, cyano, carboxy, aminocarbonyl, N—(C1-6alkyl)aminocarbonyl, N,N-di-(C1-6alkyl)aminocarbonyl, where the alkyl groups of N,N-di-(C1-6alkyl)aminocarbonyl may be the same or different, or R4 and R5, together with the phenyl ring to which the are attached, form a five- to eight-membered monoheterocyclic ring, where the ring so-formed by R4 and R5 may be unsubstituted, or substituted with one or two substituents independently selected from the group consisting of C1-6alkyl, amino(C1-3)alkyl, N—(C1-6alkyl)amino(C1-3)alkyl, N,N-di-(C1-6alkyl)amino(C1-3)alkyl, where the alkyl groups of N,N-di-(C1-6alkyl)amino(C1-3)alkyl may be the same or different, alkoxy(C1-6)alkyl, hydroxyl, hydroxy(C1-6)alkyl, (C1-6alkyl)sulfonyl, (C1-6alkyl)sulfonyl(C1-3)alkyl, heterocyclyl, amino, (C1-6)alkylamino, di-(C1-6)alkylamino, where the alkyl groups of di-(C1-6)alkylamino may be the same or different, carboxy, aminocarbonyl, N—(C1-6alkyl)aminocarbonyl, N,N-di-(C1-6alkyl)aminocarbonyl, where the alkyl groups of N,N-di-(C1-6alkyl)aminocarbonyl may be the same or different, aminocarbonyl(C1-3)alkyl, N—(C1-6)alkylaminocarbonyl(C1-3)alkyl, N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl, where the (C1-6)alkyl groups of N,N-di-(C1-6)alkylaminocarbonyl(C1-3)alkyl may be the same or different, and aminosulfonyl; and —X— is —CH═CH—, —CH2CH2—, —NH—CO—, —CONH— or —(CH(OH))2—; or a pharmaceutically acceptable salt thereof. |
