COMPOUNDS AND ANTI-TUMOR NQO1 SUBSTRATES

摘要

Compounds of Formula (I) can be selectively lethal toward a variety of different cancer cell types. The compounds are useful for the management, treatment, control or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy.

主权项

1. A compound of the Formula (I):wherein
R1, R2, R3, and R4 are each independently —H or —X—R; each X is independently a direct bond or a bridging group, wherein the bridging group is —O—, —S—, —NH—, —C(═O)—, —O—C(═O)—, —C(═O)—O—, —O—C(═O)—O—, or a linker of the formula -W-A-W-, wherein each W is independently —N(R′)C(═O)—, —C(═O)N(R′)—, —OC(═O)—, —C(═O)O—, —O—, —S—, —S(O)—, —S(O)2—, —N(R′)—, —(═O)—, —(CH2)n— where n is 1-10, or a direct bond, wherein each R′ is independently H, (C1-C6)alkyl, or a nitrogen protecting group; and each A is independently (C1-C20)alkyl, (C2-C16)alkenyl, (C2-C16)alkynyl, (C3-C8)cycloalkyl, (C6-C10)aryl, —(OCH2—CH2)n— where n is 1 to about 20, —C(O)NH(CH2)n— wherein n is 1 to about 6, —OP(O)(OH)O—, —OP(O)(OH)O(CH2)n— wherein n is 1 to about 6, or (C1-C20)alkyl, (C2-C16)alkenyl, (C2-C16)alkynyl, or —(OCH2—CH2)n— interrupted between two carbons, or between a carbon and an oxygen, with a cycloalkyl, heterocycle, or aryl group; each R is independently alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, (cycloalkyl)alkyl, (heterocycloalkyl)alkyl, (cycloalkyl)heteroalkyl, (heterocycloalkyl)heteroalkyl, aryl, heteroaryl, (aryl)alkyl, (heteroaryl)alkyl, hydrogen, hydroxy, hydroxyalkyl, alkoxy, (alkoxy)alkyl, alkenyloxy, alkynyloxy, (cycloalkyl)alkoxy, heterocycloalkyloxy, amino, alkylamino, aminoalkyl, acylamino, arylamino, sulfonylamino, sulfinylamino, —CORx, —COORx, —CONHRx, —NHCORx, —NHCOORx, —NHCONHRx, —N3, —CN, —NC, —NCO, —NO2, —SH, -halo, alkoxycarbonyl, alkylaminocarbonyl, sulfonate, sulfonic acid, alkylsulfonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, aminosulfonyl, RxS(O)Ry—, RxS(O)2Ry—, RxC(O)N(Rx)Ry—, RxSO2N(Rx)Ry—, RxN(Rx)C(O)Ry—, RxN(Rx)SO2Ry—, RxN(Rx)C(O)N(Rx)Ry—, carboxaldehyde, acyl, acyloxy, —OPO3H2, —OPO3Z2 where Z is an inorganic cation, or saccharide; where each Rx is independently H, OH, alkyl or aryl, and each Ry is independently a group W; wherein any alkyl or aryl can be optionally substituted with one or more hydroxy, amino, cyano, nitro, or halo groups; or a salt or solvate thereof; provided that when R1, R2, and R3 are methyl, R4 is not H or methyl; and provided that when R1, R3, and R4 are methyl, the group —X—R of R2 is not acyloxy.