- 6,9-Bisbenzoisoquinoline-5,10-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluations
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Synthetic procedures have been developed which lead to the 2-aza congeners 3 and several related N-oxides 4.The analoques 3 exhibited a wide range of in vitro cytotoxicity against L1210 leukemia, the human colon adenocarcinoma cell line LoVo, and the doxorubicin resistant LoVo/DX cell line.Selected analogues of 3 showed significant P388 antileukemic activity in mice with 3c exhibiting high activity.This activity was also retained in the related N-oxide 4a.These heterocyclic bioisosteric models are representative of the first anthracene-9,10-diones which display antileukemic activity comparable to mitoxantrone.
- Krapcho, A. Paul,Petry, Mary E.,Getahun, Zelleka,Landi, John J.,Stallman, John,et al.
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p. 828 - 837
(2007/10/02)
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- 6,9 Bis(substituted-amino)benzo-[g]isoquinoline-5,10-diones
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A compound according to formula (I): wherein R is, C1-C10 alkyl; phenyl or C7-C10 aralkyl;, C2-C10 aklyl substituted with one or two substituents selected from the group consisting of OR1 and -NR2R3;, C2-C10 alkyl interrupted by one or two oxygen atoms or by a member selected from the group consisting of -NR4-, cis-CH=CH, trans-CH=CH- and -C=C-, and optionally substituted with one or two hydroxy (OH) or -NR2R3 groups; and wherein, R1 is selected from the group consisting of hydrogen, C1-C6 alkyl, phenyl, C7-C10 aralkyl, -CHO, -COR5-, -COOR5, -S(O2)R5 and C2-C6 alkyl optionally substituted with -NR2R3;, R2 and R3 are the same or different and are selected from the group consisting of hydrogen, C1-C10 alkyl, C7-C10 aralkyl, phenyl, C2-C10 alkyl substituted with one or two hydroxy (OH) groups, -CHO, -COR5, -COOR5, and -S(O2)R5, R2 and R3 taken together with the nitrogen atom to which they are bound form an ethyleneimine ring or a 5- or 6-membered aromatic or non-aromatic heterocyclic ring optionally containing another heteroatom selected from the group consisting of sulfur, oxygen and nitrogen, R2 is H and R3 is -C(=NH)NH2 or R2 is -C(=NH)NH2 and R3 is H;, R4 is selected from the group consisting of hydrogen, C1-C10 alkyl, C2-C10 hydroxyalkyl, C2-C10 alkyl substituted with -NR2R3, C7-C10 aralkyl, phenyl, -COR5, -COOR5 and -S(O2)R5;, R5 is selected from the group consisting of C1-C10 alkyl, C7-C10 aralkyl, α-, β-, or γ-naphthyl, phenyl, o-, m-, or p-tolyl as free bases and their salts with pharmaceutically acceptable acids, have been found to have cytostatic and anti-tumor activity.
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