Prodrug using nitroimidazole

Patent metadata

Field	Value
Publication number	US-9655975-B2
Application number	US-201314376459-A
Country	US
Kind code	B2
Filing date	Feb 13, 2013
Priority date	Feb 13, 2012
Publication date	May 23, 2017
Grant date	May 23, 2017

Abstract

Provided is a prodrug of 2-nitro-1-imidazolepropionic acid and a therapeutically active organic compound having on the molecule an amino group, a cyclic amino group or a hydroxyl group, particularly a prodrug in which the therapeutically active organic compound is selected from among antitumor agents. The prodrug cleaves specifically under hypoxic conditions in vivo to exhibit the inherent therapeutic activity.

First claim

The invention claimed is:

1. A compound represented by general formula (I),

wherein Z is of formula (a)

or of formula (b)
—O—R3  (b),

R1 being a residue of an amino group-bearing therapeutically active organic compound after removal of the amino group therefrom and R2 being a hydrogen atom, or R1 and R2, taken together with the adjoining nitrogen atom, being a residue of a therapeutically active organic compound having a cyclic amino group; and
R3 being a residue of a hydroxyl group-bearing therapeutically active organic compound after removal of the hydroxyl group therefrom,
wherein
the amino group-bearing therapeutically active organic compound is selected from the group consisting of doxorubicin and gemcitabine;
the therapeutically active organic compound having a cyclic amino group is represented by 5-fluorouracil;
the hydroxyl group-bearing therapeutically active organic compound is selected from the group consisting of doxorubicin and gemcitabine; and
the moiety corresponding to Z of general formula (I) is cleaved in a reducing environment,

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 which has a formula as follows:

3. The compound according to claim 1 which has a formula as follows:

4. The compound according to claim 1 which has one of the following two formulae:

Assignees

• Univ Tsukuba

Inventors

• Nagasaki Yukio
• Ikeda Yutaka
• Hisano Hikaru

Classifications

• A61K31/58

  containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) · CPC title

• C07H15/24

  Condensed ring systems having three or more rings · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• C07D475/08

  with a nitrogen atom directly attached in position 2 · CPC title

• C07H19/06

  Pyrimidine radicals · CPC title