Anticancer agent

Patent metadata

Field	Value
Publication number	US-10377730-B2
Application number	US-201815987525-A
Country	US
Kind code	B2
Filing date	May 23, 2018
Priority date	Jun 9, 2014
Publication date	Aug 13, 2019
Grant date	Aug 13, 2019

Abstract

The problem of the present invention is to provide a useful prodrug compound of a naphthofuran compound. The present invention relates to a compound represented by the formula (IA):

[wherein each symbol is as described in the DESCRIPTION] or a pharmaceutically acceptable salt thereof.

First claim

The invention claimed is:

1. A compound represented by the formula (IA):

wherein
each R 1 is independently
hydrogen,
halogen,
hydroxy,
amino,
cyano,
nitro,
C 1-12 alkyl,
C 2-6 alkenyl,
C 2-6 alkynyl,
C 3-7 cycloalkyl,
C 3-7 cycloalkenyl,
aryl,
a heterocyclyl group,
C 1-6 alkoxy,
aryloxy,
C 1-6 alkylthio, or
arylthio, or
two R 1 bonded to the adjacent carbon atoms on a benzene ring are optionally joined to form C 1-4 alkylenedioxy,
R 2 is
C 1-12 alkyl optionally substituted by substituent(s) selected from substituent group α,
C 2-6 alkenyl optionally substituted by substituent(s) selected from substituent group α,
C 2-6 alkynyl optionally substituted by substituent(s) selected from substituent group α,
C 3-7 cycloalkyl optionally substituted by substituent(s) selected from substituent group α,
aryl optionally substituted by substituent(s) selected from substituent group α,
aryl C 1-6 alkyl optionally substituted by substituent(s) selected from substituent group α, or
heterocyclyl optionally substituted by substituent(s) selected from substituent group α,
R 3 is
hydrogen,
halogen,
cyano,
nitro,
C 1-12 alkyl,
C 2-6 alkenyl,
C 2-6 alkynyl,
C 3-7 cycloalkyl,
C 3-7 cycloalkenyl,
aryl,
heterocyclyl,
C 1-6 alkoxy,
aryloxy,
C 1-6 alkylthio, or
arylthio,
n is an integer of 1-4 when R 1 is hydrogen,
n is an integer of 1 or 2 when R 1 is not hydrogen, and
the substituent group α consists of
halogen,
hydroxy,
optionally substituted amino,
carboxy,
C 1-6 alkoxycarbonyl,
sulfo group,
phosphoric acid group,
di C 1-6 alkyl phosphoric acid group,
cyano,
optionally substituted C 1-6 alkyl,
C 3-7 cycloalkyl,
C 3-7 cycloalkyl C 1-6 alkyl,
optionally substituted C 1-6 alkoxy,
C 1-6 alkylthio,
optionally substituted aryl,
optionally substituted aryloxy,
aryl C 1-6 alkoxy,
optionally substituted heterocyclyl,
optionally substituted C 1-6 alkylcarbonyl,
heterocyclylcarbonyl,
optionally substituted C 1-6 alkylcarbonyloxy,
optionally substituted C 3-7 cycloalkylcarbonyloxy,
arylcarbonyloxy,
monocyclic heterocyclylcarbonyloxy,
optionally substituted C 1-6 alkoxycarbonyloxy,
optionally substituted heterocyclyl C 1-6 alkoxycarbonyloxy,
C 3-7 cycloalkyloxycarbonyloxy,
heterocyclyloxycarbonyloxy,
optionally substituted heterocyclyloxy,
tri C 1-6 alkylammonio,
optionally substituted C 1-6 alkylsulfonyl and
C 1-6 alkylsulfamoylcarbonyl,

or a pharmaceutically acceptable salt thereof.

2. A compound represented by the formula (I):

wherein
R 1 is
hydrogen or halogen,
R 2 is
C 1-12 alkyl optionally substituted by substituent(s) selected from substituent group α,
C 2-6 alkenyl optionally substituted by substituent(s) selected from substituent group α,
C 2-6 alkynyl optionally substituted by substituent(s) selected from substituent group α,
C 3-7 cycloalkyl optionally substituted by substituent(s) selected from substituent group α,
aryl optionally substituted by substituent(s) selected from substituent group α,
aryl C 1-6 alkyl optionally substituted by substituent(s) selected from substituent group α, or
a heterocyclyl group optionally substituted by substituent(s) selected from substituent group α,
n is an integer of 1-4 when R 1 is hydrogen,
n is an integer of 1 or 2 when R 1 is not hydrogen, and
the substituent group α consists of
halogen,
hydroxy,
optionally substituted amino,
carboxy,
C 1-6 alkoxycarbonyl,
sulfo group,
phosphoric acid group,
di C 1-6 alkyl phosphoric acid group,
cyano,
optionally substituted C 1-6 alkyl,
C 3-7 cycloalkyl,
C 3-7 cycloalkyl C 1-6 alkyl,
optionally substituted C 1-6 alkoxy,
C 1-6 alkylthio,
optionally substituted aryl,
optionally substituted aryloxy,
aryl C 1-6 alkoxy,
optionally substituted heterocyclyl,
optionally substituted C 1-6 alkylcarbonyl,
heterocyclylcarbonyl,
optionally substituted C 1-6 alkylcarbonyloxy,
optionally substituted C 3-7 cycloalkylcarbonyloxy,
arylcarbonyloxy,
monocyclic heterocyclylcarbonyloxy,
optionally substituted C 1-6 alkoxycarbonyloxy,
optionally substituted heterocyclyl C 1-6 alkoxycarbonyloxy,
C 3-7 cycloalkyloxycarbonyloxy,
heterocyclyloxycarbonyloxy,
optionally substituted heterocyclyloxy,
tri C 1-6 alkylammonio,
optionally substituted C 1-6 alkyl sulfonyl and
C 1-6 alkyl sulfamoylcarbonyl,

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2 , wherein the substituent group α consists of
halogen,
hydroxy,
optionally substituted amino,
carboxy,
C 1-6 alkoxycarbonyl,
sulfo group,
phosphoric acid group,
di C 1-6 alkyl phosphoric acid group,
cyano,
C 1-6 alkyl,
C 3-7 cycloalkyl,
C 1-6 alkoxy,
optionally substituted aryl,
optionally substituted aryloxy,
aryl C 1-6 alkoxy,
optionally substituted heterocyclyl,
optionally substituted C 1-6 alkylcarbonyl,
heterocyclylcarbonyl,
optionally substituted C 1-6 alkylcarbonyloxy,
optionally substituted C 3 -7 cycloalkylcarbonyloxy,
monocyclic heterocyclylcarbonyloxy,
optionally substituted C 1-6 alkoxycarbonyloxy,
optionally substituted heterocyclyl C 1-6 alkoxycarbonyloxy,
C 3-7 cycloalkyloxycarbonyloxy,
heterocyclyloxycarbonyloxy,
optionally substituted heterocyclyloxy and
tri C 1-6 alkylammonio,

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 2 , wherein
R 2 is C 1-6 alkyl optionally substituted by substituent(s) selected from substituent group α, C 2-6 alkenyl optionally substituted by substituent(s) selected from substituent groupα, C 3-7 cycloalkyl optionally substituted by substituent(s) selected from substituent group α, aryl optionally substituted by substituent(s) selected from substituent group α, aryl C 1-6 alkyl optionally substituted by substituent(s) selected from substituent group α, or heterocyclyl optionally substituted by substituent(s) selected from substituent group α, and
the substituent group α consists of halogen, hydroxy, optionally substituted amino, carboxy, sulfo group, phosphoric acid group, cyano, C 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy, aryl and heterocyclyl,

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 2 , wherein R 2 is
(1) C 1-6 alkyl optionally substituted by substituent(s) selected from hydroxy, optionally substituted amino, carboxy, sulfo group, phosphoric acid group, di C 1-6 alkyl phosphoric acid group, heterocyclyl group, optionally

Assignees

• Kyoto Pharma Ind
• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Yoshimura Yoshinobu
• Kasai Masayasu
• Shoji Yoshimichi
• Takeda Shigemitsu

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D407/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D307/92 Primary

  Naphthofurans; Hydrogenated naphthofurans · CPC title

• C07H7/06

  Heterocyclic radicals · CPC title

• C07H15/26

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title