α,β-unsaturated amide compound

Patent metadata

Field	Value
Publication number	US-11447471-B2
Application number	US-201816625446-A
Country	US
Kind code	B2
Filing date	Jun 22, 2018
Priority date	Jun 23, 2017
Publication date	Sep 20, 2022
Grant date	Sep 20, 2022

Abstract

An object of the present invention is to provide an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like. The α,β-unsaturated amide compound represented by the following formula (I) or a pharmaceutically acceptable salt or the like thereof has anticancer activity and the like:

[wherein, “A” represents optionally substituted heterocyclic diyl,
R 1 represents hydrogen atom or optionally substituted lower alkyl, R 2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents —O—, —S—, —SO 2 —, —NR X1 — (wherein, R X1 represents hydrogen atom or lower alkyl), —CHR X2 — (wherein, R X2 represents hydrogen atom or hydroxy), —CH═CH—, −CO— or —NH—CO—, and n1 and n2 are the same or different, and each represents 0 or 1].

First claim

The invention claimed is:

1. An α,β-unsaturated amide compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof:

wherein R 1 represents a hydrogen atom or an optionally substituted lower alkyl,
R 2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group,
X represents —O—, —S—, —SO 2 —, —NR X1 — wherein R X1 represents a hydrogen atom or lower alkyl, —CHR X2 — wherein R X2 represents a hydrogen atom or hydroxy, —CH═CH—, —CO— or —NH—CO—,
n1 and n2 are the same or different, and each represents 0 or 1, and
A represents optionally substituted heterocyclic diyl,
wherein
the heterocyclic diyl in the optionally substituted heterocyclic diyl is heterocyclic diyl selected from the group consisting of benzoxazolediyl, benzothiazolediyl, 2,3-dihydrobenzothiophenediyl, 3,4-dihydropyranopyridinediyl, 2,3,4,5-tetrahydrobenzoxazepinediyl, 2,3,4,5-tetrahydrobenzoxepinediyl and 2,3-dihydrobenzofurandiyl, and
the benzothiazolediyl is benzothiazolediyl represented by the following formula (A2-1) or (A2-2):

wherein
-[X] represents bonding position of the group represented in formula (A-1):

wherein X, R 2 and n2 are each the same as the definition described above, and
-[ACP] represents bonding position of the group represented in formula (A-2):

wherein R 1 and n1 are each the same as the definition described above, and
the 2,3-dihydrobenzofurandiyl is 2,3-dihydrobenzofurandiyl selected from the group consisting of the following formulae (A8-1), (A8-2) and (A8-3):

wherein -[X] and -[ACP] are each the same as the definition described above.

2. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is a hydrogen atom.

3. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is optionally substituted aryl or optionally substituted aromatic heterocyclic group.

4. A pharmaceutical composition, comprising:
the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 1 ; and
a carrier.

5. A therapeutic agent comprising the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.

6. A method for treating cancer, comprising:
administering the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

7. A medicine, comprising the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 1 .

8. The method according to claim 6 , wherein the cancers at least one selected from the group consisting of mesothelioma, lung cancer, ovarian cancer, and liver cancer.

Assignees

• Kyowa Kirin Co Ltd

Inventors

• Danjo Tomohiro
• Yamada Hiroki
• Nakajima Takahiro

Classifications

• C07D263/56

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2 · CPC title

• C07D307/86

  with an oxygen atom directly attached in position 7 · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D405/12 Primary

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

• C07D217/24

  Oxygen atoms · CPC title