Phosphatidylinositol-3-kinase inhibitor and pharmaceutical composition

Patent metadata

Field	Value
Publication number	US-9963482-B2
Application number	US-201214348799-A
Country	US
Kind code	B2
Filing date	Sep 25, 2012
Priority date	Sep 30, 2011
Publication date	May 8, 2018
Grant date	May 8, 2018

Abstract

A substance contains a phosphatidylinositol-3-kinase (PI3K) inhibitor including a depsipeptide-class compound represented by formula (1), or a physiologically acceptable salt thereof that combines a PI3K inhibitory effect and an HDAC inhibitory effect to provide an anti-cancer pharmaceutical composition for the treatment of an intractable cancer.

First claim

The invention claimed is:

1. A pharmaceutical composition for treatment of refractory cancer comprising a phosphatidylinositol-3-kinase (PI3K) inhibitor as an effective component, wherein the PI3K inhibitor is a depsipeptide compound having a formula selected from the group consisting of the following formulae 5 to 12 and 14 to 20, and a physiologically acceptable salt thereof:

2. A depsipeptide compound represented by the following formula 1:

wherein A is —CONH—, R 1 is naphthyl alkyl group, and R 2 and R 3 may be the same or different from each other and each represents a hydrogen atom, a lower alkyl group, a lower alkylidene group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, wherein the lower alkyl group is a linear or branched alkyl group having 1 to 6 carbon atoms and the lower alkylidene group is a linear or branched alkylidene group having 1 to 6 carbon atoms; or a physiologically acceptable salt thereof.

3. The depsipeptide compound or the physiologically acceptable salt thereof according to claim 2 , wherein R 1 in the formula 1 is naphthyl methyl group.

4. A pharmaceutical composition for treatment of refractory cancer, comprising as an effective component, the depsipeptide compound or a physiologically acceptable salt thereof according to claim 2 .

5. A method for treating refractory colon or prostate cancer by inhibiting phosphatidylinositol-3-kinase (PI3K), comprising: administering to a subject in need thereof the pharmaceutical composition according to claim 1 .

6. A method for treating refractory colon or prostate cancer by inhibiting phosphatidylinositol-3-kinase (PI3K), comprising: administering to a subject in need thereof the depsipeptide compound or the physiologically acceptable salt thereof according to claim 2 .

Assignees

• Univ Tohoku

Inventors

• SAIJO Ken
• Ishioka Chikashi
• Katoh Tadashi

Classifications

• C07K5/12 Primary

  Cyclic peptides {with only normal peptide bonds in the ring} · CPC title

• A61K38/06

  Tripeptides · CPC title

• C07K5/123

  Tripeptides · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title