公开(公告)号：WO1992021661A1

公开(公告)日：1992-12-10

申请号：PCT/US1992004611

申请日：1992-05-28

Applicant: GLAXO INC.

Inventor： GLAXO INC. ,  LUZZIO, Michael, J. ,  BESTERMAN, Jeffrey, M. ,  EVANS, Michael, G. ,  JOHNSON, M., Ross ,  DEZUBE, Milana ,  PROFETA, Salvatore, Jr.

IPC: C07D221/18

CPC classification number: C07D221/18 ,  C07D471/04 ,  C07D491/04 ,  C07D491/14

Abstract: The present invention relates to certain substituted tetracyclic fused quinoline derivatives of formula (I), wherein R1 is hydrogen, hydroxy, fluoro, chloro, bromo, iodo, methoxy or amino; R2 is hydrogen, hydroxy, methoxy or amino; R3 is hydrogen, hydroxy, methoxy, methoxymethoxy, amino, -OCONH¿2?, [2(5H)-3,4-dihydro-3-oxyfuranone], 2-hydroxyethoxy, 2-aminoethoxy, 3-hydroxypropoxy or 3-aminopropoxy; or taken together with R?2 or R4¿, methylenedioxy or ethylenedioxy; R4 is hydrogen, hydroxy or amino; Z is -CH¿2?-, -O- or -NH-; and a) X?1¿ is hydrogen; X2 is hydrogen, hydroxy, fluoro, chloro, bromo, iodo or methoxy; and X3 is hydrogen or hydroxy; or b) X2 taken together with X3 is methylenedioxy or etylenedioxy, and X1 is hydrogen or a pharmaceutically acceptable salt thereof provided that: i) at least one of R1 through R4 is other than hydrogen; ii) when R1 is methoxy, R2 is hydroxy or methoxy, R3 is hydrogen or methoxy and R4 is hydrogen; iii) when R2 is hydroxy, methoxy or amino, R3 is hydrogen, hydroxy or methoxy, and R4 is hydrogen; iv) when R4 is hydroxy or amino, R?1 and R3¿ are hydrogen and R2 is hydroxy or amino; and v) when R1 is fluoro, chloro, iodo or amino, R2 is hydrogen, hydroxy or methoxy, R3 is hydrogen, hydroxy or methoxy and R4 is hydrogen and the use of these compounds as topoisomerase inhibitors and antitumor agents.

公开(公告)号：WO1992012981A1

公开(公告)日：1992-08-06

申请号：PCT/US1992000581

申请日：1992-01-24

Applicant: GLAXO INC.

Inventor： GLAXO INC. ,  LUZZIO, Michael, J. ,  BESTERMAN, Jeffrey, M. ,  EVANS, Michael, G. ,  ROSS, Johnson, M.

IPC: C07D491/056

CPC classification number: C07D491/04

Abstract: The present invention relates to the compounds of formula (I), wherein: R1 is hydrogen, hydroxy or amino; R2 is hydrogen, hydroxy, methoxy or methoxymethoxy; R3 is hydrogen, hydroxy, amino, methoxy, methoxymethoxy or, taken together with R2, methylenedioxy (also known as 1,3 dioxolo); R4 is hydrogen, hydroxy, methoxy, methoxymethoxy, benzyl, di(C¿1-4?)alkylaminomethyl or, taken together with R?3¿, methylenedioxy; R5 is hydrogen or hydroxy; provided that at least one of R1 through R5 is other than hydrogen; and i) X2 is hydroxy or methoxy with X?1, X3 and X4¿ being hydrogen or ii) X1 taken together with X2, X2 taken together with X3 or X3 taken together with X4, is methylenedioxy, provided that each of the remaining respective X?1, X2, X3 and X4¿ substituents are hydrogen, intermediates in the synthesis of them, pharmaceutical formulation containing them, their use as inhibitors of topoisomerase and their use in the treatment of tumors.