| 摘要 |
The invention described herein pertains to substituted azaindenoisoquinoline compounds, in particular 7-, 8-, 9-, and 10-azaindenoisoquinoline compounds, which are inhibitors of topoisomerase I, processes and intermediates for their syntheses, pharmaceutical compositions of the compounds, and methods of using them in the treatment of cancer. |
| 主权项 |
1. A compound of the formulaor a pharmaceutically acceptable salt thereof, wherein:
each of RA, RB, RC and RD is independently hydrogen, hydroxy, acyloxy, halo, cyano, nitro, optionally substituted (1-6C) alkyl or optionally substituted (1-6C) alkoxy; or two adjacent RA, RB, RC and RD radicals form a methylenedioxy or ethylenedioxy group and each of the others is defined as above; RE is —(CH2)nRN; n is 2, 3 or 4; RN is 1-imidazolyl, 1,2,4-triazol-2-yl or azido; or RN is —NR1R2; in which each of R1 and R2 is independently hydrogen or (1-3C) alkyl or in which one of R1 and R2 is methyl and the other of R1 and R2 is 2-hydroxyethyl or methyl; or —NR1R2 forms a pyrrolidino, piperidino, piperazino, morpholino or thiomorpholino group, each of which may bear one or more methyl substituents; in which a pyrrolidino or piperidino may bear a hydroxy substituent on a carbon not bound to nitrogen; and in which a pyrrolidino or piperidino may be a 3,4-didehydro moiety; W is N or CRW; X is N or CRX; Y is N or CRY; Z is N or CRZ; one of W, X, Y and Z is N, and each of the others of W, X, Y and Z is CRW, CRX, CRY or CRZ, respectively; and each of RW, RX, RY and RZ, is independently hydrogen, (1-3C) alkyl, (1-3C) alkoxy, or acyloxy. |
