COVALENT CONJUGATES OF TOPOISOMERASE I AND TOPOISOMERASE II INHIBITORS

Title:

COVALENT CONJUGATES OF TOPOISOMERASE I AND TOPOISOMERASE II INHIBITORS

Document Type and Number:

WIPO Patent Application WO1998040104

Kind Code:

A3

Abstract:

The present invention provides covalent conjugates of topoisomerase I and topoisomerase II inhibitors. Such compounds have a structure according to formula I:wherein:TI is a topoisomerase I inhibitor such as a camptothecin group;TII is a topoisomerase II inhibitor such as an amsacrine, ellipticine, epipodophyllotoxin, or anthracycline antibiotic group; andL is a linking group.The compounds are useful for inhibiting topoisomerase I and II enzymes, for promoting cellular differentiation, and for treating cancer.

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Inventors:

CHENG YUNG-CHI
GUO XIN
LEE KUO-HSIUNG
BASTOW KENNETH F
WANG HUI-KANG

Application Number:

PCT/US1998/004852

Publication Date:

February 11, 1999

Filing Date:

March 11, 1998

Export Citation:

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Assignee:

UNIV YALE (US)
UNIV NORTH CAROLINA (US)

International Classes:

A61K47/48; (IPC1-7): A61K47/48

Domestic Patent References:

WO1996023794A1	1996-08-08
WO1995020567A1	1995-08-03

Foreign References:

EP0321122A2	1989-06-21
US5332811A	1994-07-26

Other References:

GUO X ET AL: "Novel biochemical and antitumor activity of the camptothecin-4beta-amino-4'-O-demethyl epipodophyllotoxin conjugates (Meeting abstract).", PROC ANNU MEET AM ASSOC CANCER RES;38:A4108 1997, XP002071384
DATABASE MEDLINE US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; BASTOW KF ET AL: "Antitumor agents--CLXXIII. Synthesis and evaluation of camptothecin-4 beta-amino-4'-O-demethyl epipodophyllotoxin conjugates as inhibitors of mammalian DNA topoisomerases and as cytotoxic agents.", XP002072004
PODDEVIN B ET AL: "Dual topoisomerase I and II inhibition by intoplicine (RP-60475), a new antitumor agent in early clinical trials.", MOL PHARMACOL, OCT 1993, 44 (4) P767-74, UNITED STATES, XP002071386

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