Title:
抗腫瘍薬である新規インデノイソキノリン類
Document Type and Number:
Japanese Patent JP4580556
Kind Code:
B2
Abstract:
A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity vs. topoisomerase I. The two most cytotoxic indenoisoquinolines proved to be cis-6-ethyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8,9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline and cis-6-allyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8,9-(methylenedioxy)-5,11-dioxo-(11H)indeno[1,2-c]isoquinoline. Two of the most potent topoisomerase I inhibitors were 6-(3-carboxy-1-propyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (26) and 6-ethyl-2,3-dimethoxy-8,9-(methylenedioxy)11H-indeno[1,2-c]isoquinolinium chloride (27). Two additional potent topoisomerase I inhibitors, 6-allyl-5,6-dihydro-2,3-dimethoxy-8,9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (13c) and 5,6-dihydro-6-(4-hydroxybut-1-yl)-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-(11H)indeno[1,2-c]isoquinoline (19a), did not unwind DNA and did not affect topoisomerase II.
Inventors:
Cushman, Mark S.
Nagafuji, Pamela M.
Jaya Raman, Musasami
Pommier, Eve Gee.
Nagafuji, Pamela M.
Jaya Raman, Musasami
Pommier, Eve Gee.
Application Number:
JP2000575513A
Publication Date:
November 17, 2010
Filing Date:
October 14, 1999
Export Citation:
Assignee:
Purdue Research Foundation
THE UNITED STATES OF AMERICA
THE UNITED STATES OF AMERICA
International Classes:
C07D221/18; A61K31/472; A61K31/473; A61K31/4741; A61P35/00; C07D217/26; C07D491/056; C07D491/22
Domestic Patent References:
| JP9143166A | ||||
| JP7500581A |
Other References:
CHEM.ABSTR,1982年 6月 7日,vol.96, No.23,653-654
J.ORG.CHEM,1998年 8月21日,vol.63, No.17,572-573
J.MED.CHEM.,1985年,vol.28,1031-1036
MUTATION RESEARCH,1993年,vol.301,207-212
J.ORG.CHEM,1966年 4月 1日,vol.31,1004-1006
J.ORG.CHEM,1968年,vol.33, No.7,2861-2868
J.ORG.CHEM,1998年 8月21日,vol.63, No.17,572-573
J.MED.CHEM.,1985年,vol.28,1031-1036
MUTATION RESEARCH,1993年,vol.301,207-212
J.ORG.CHEM,1966年 4月 1日,vol.31,1004-1006
J.ORG.CHEM,1968年,vol.33, No.7,2861-2868
Attorney, Agent or Firm:
Takashima Ichi