JPWO2017184774A5

JPWO2017184774A5 -

Info

Publication number: JPWO2017184774A5
Application number: JP2018554700A
Authority: JP
Publication date: 2022-07-19

Description

他の実施形態では、ＨＤＡＣ阻害剤及びブルトン型チロシンキナーゼ（ＢＴＫ）阻害剤の１つまたは両方は、治療有効量以下の量または薬用量で投与される。治療有効量以下の量は、単独で患者に投与したとき、経時的に標的の生物学的活性を完全に阻害しないＨＤＡＣ阻害剤（例えば、式ＩまたはＩＩの化合物）またはブルトン型チロシンキナーゼ（ＢＴＫ）阻害剤の量である。 In other embodiments, one or both of the HDAC inhibitor and Bruton's tyrosine kinase (BTK) inhibitor is administered in an amount or dosage less than or equal to the therapeutically effective amount . A therapeutically effective amount or less is an HDAC inhibitor (eg, a compound of formula I or II) or Bruton's tyrosine kinase (eg, a compound of formula I or II) that does not completely inhibit the biological activity of the target over time when administered to the patient alone. BTK) The amount of inhibitor.

ＨＤＡＣ阻害剤及びブルトン型チロシンキナーゼ（ＢＴＫ）阻害剤の配合物は、治療量または治療量以下の量のどちらの投与においても慢性リンパ性白血病の治療に有効でなければならない。例えば、治療量以下の量のブルトン型チロシンキナーゼ（ＢＴＫ）阻害剤は、式ＩまたはＩＩの化合物（ＨＤＡＣ６選択的阻害剤）と組み合わせたとき、その配合物が慢性リンパ性白血病の治療に有効である治療有効量であり得る。 The combination of HDAC inhibitor and Bruton's tyrosine kinase (BTK) inhibitor must be effective in treating chronic lymphocytic leukemia at either therapeutic or sub-therapeutic doses . For example , a subtherapeutic amount of Bruton's tyrosine kinase (BTK) inhibitor, when combined with a compound of formula I or II (HDAC6 selective inhibitor), is effective in treating chronic lymphocytic leukemia. Can be a therapeutically effective amount.

Claims

Chronic lymphocytic subjects in need thereof, including therapeutically effective amounts of histone deacetylase 6 (HDAC6) selective inhibitors and Bruton's tyrosine kinase (BTK) inhibitors or pharmaceutically acceptable salts thereof. A pharmaceutical formulation for the treatment of leukemia
The HDAC6 selective inhibitor is the following compound A :

Or its pharmaceutically acceptable salt ; or
The following compound B:

Or its pharmaceutically acceptable salt,
The BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof.
The HDAC6 selective inhibitor and the BTK inhibitor are each administered in an amount equal to or less than a therapeutically effective amount .
Pharmaceutical formulation.

The HDAC6 selective inhibitor is the following compound A:

The pharmaceutical formulation according to claim 1 , which is a pharmaceutically acceptable salt thereof.

The HDAC6 selective inhibitor is the following compound B:

The pharmaceutical formulation according to claim 1, further comprising a pharmaceutically acceptable carrier.

The HDAC6 selective inhibitor is the following compound A:

The pharmaceutical formulation according to claim 1, wherein the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof, which is a pharmaceutically acceptable salt thereof.

The HDAC6 selective inhibitor is the following compound B:

The pharmaceutical formulation according to any one of claims 1 to 6 , wherein the HDAC6 selective inhibitor and the BTK inhibitor are in the same formulation.

The pharmaceutical formulation according to any one of claims 1 to 6 , wherein the HDAC6 selective inhibitor and the BTK inhibitor are in separate formulations.

The pharmaceutical formulation according to any one of claims 1 to 6 , which is used for the treatment of chronic lymphocytic leukemia in a patient.

Chronic lymphocytic subjects in need thereof, including therapeutically effective amounts of histone deacetylase 6 (HDAC6) selective inhibitors and Bruton's tyrosine kinase (BTK) inhibitors or pharmaceutically acceptable salts thereof. A pharmaceutical composition for treating leukemia,
The HDAC6 selective inhibitor is the following compound A :

Or its pharmaceutically acceptable salt ; or
The following compound B:

Or its pharmaceutically acceptable salt,
The BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof.
The HDAC6 selective inhibitor and the BTK inhibitor are each administered in an amount equal to or less than a therapeutically effective amount .
Pharmaceutical composition.

The HDAC6 selective inhibitor is the following compound A:

The pharmaceutical composition according to claim 10 , which is a pharmaceutically acceptable salt thereof.

The HDAC6 selective inhibitor is the following compound B:

The pharmaceutical composition according to claim 10 , further comprising a pharmaceutically acceptable carrier.

The HDAC6 selective inhibitor is the following compound A:

10. The pharmaceutical composition of claim 10 , wherein the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof, which is a pharmaceutically acceptable salt thereof.

The HDAC6 selective inhibitor is the following compound B:

The pharmaceutical composition according to any one of claims 10 to 15 , further comprising a pharmaceutically acceptable carrier.

The pharmaceutical composition according to any one of claims 10 to 16 , which is used for treating chronic lymphocytic leukemia in a patient.