Substituted pyrrolo2,1-aphthalazines and benzogpyrrolo2,1-aphthalazines for the treatment of cancer

摘要

Disclosed herein are novel bifunctional compounds and their uses for the treatment and/or prophylaxis of cancers. The bifunctional compound disclosed herein has the structure of formula (I),; wherein,; optionally substituted with one or more substituents independently selected from the group consisting of halo, alkyl, haloalkyl, alkenyl, C(O)H, OH, O(alkyl), O(CO)alkyl, O(aryl), aryl, and —O(CH₂)_xN(R_b)₂;R¹ is an alkyl optionally substituted with one or more substituents independently selected from the group consisting of halo, —OR, —O(CO)CH₃, —OSO₂R, and —OCONHR;R is hydrogen, alkyl, cycloalkyl, or aryl;R² is hydrogen, alkyl, cycloalkyl, aryl or heteroaryl, in which the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of C_1-6 alkyl, O(alkyl), halo, cyano, nitro, —N(R_c)₂, OCH₂O—, O(CH₂)₂O—, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, and 4—(piperido)piperidinyl;R³ is -NR^AR^B, or -NHPhR^C, or -NR^AR^B are taken together to form pyrrolidin-l-yl, piperidin-l-yl, piperazin-l-yl, morpholin-4-yl, 4-(piperidin-l-y)piperidin-l-yl, or 4-(piperidin-4-yl)piperidin-l-yl, wherein the piperazin-l-yl or 4-(piperidin-4-yl) piperidin-l-yl is optionally substituted with one or more substituents independently selected from the group consisting of alky, and —(CH₂)_nCONH(CH₂)_mNR^AR^B;R^A and R^B are independently H or C₁-C₆ alkyl;R^C is hydrogen, halo, alkyl, alkenyl, alknyl, O(alkyl), —NHCOR_a, —NHC(O)OR_a, heterocyclyl or aryl, in which the alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halo, alkyl, haloalkyl, alkenyl C(O)H, OC(O)alkyl, O(aryl), and aryl, in which the aryl is optionally substituted with one or more substituents independently selected from the group consisting of halo, CN, C_1-6 alkyl, N(R_c)₂, NO₂, O(alkyl), —OCH₂O—, —O(CH₂)₂O—,pyrrolidinyl, pepiridinyl, piperazinyl, morpholino, and 4-(piperido)piperidinyl;R_a is C_1-6 alkyl or aryl;R_b is C_1-10 alkyl, pyrrolidin-l-yl, piperidin-l-yl, piperazin-l-yl, morpholin-4-yl, 4-(piperidin-l-yl)piperidin-l-yl, or 4-(piperidin-4-yl)piperidin-l-yl;R_c, is hydrogen or C_1-10 alkyl; and.x, n and m are independently an integral between 1 to 5.