α,β-unsaturated amide compound
The present invention provides an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like represented by the following formula (I): [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].
1. An α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof represented by the following formula (I):
R 1 represents hydrogen atom,
R 2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, and R 2 is not pyrimidinyl when X═NH,
X represents —O—, —S—, —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,
wherein “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 the following formulae (A3-1), (A3-2), (A3-3), (A3-4), (A3-5), (A3-6), (A3-7), and (A3-9):
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,
-[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.
2. An α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof represented by the following formula (I):
R 1 represents hydrogen atom,
R 2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, and R 2 is not pyrimidinyl when X═NH,
X represents —O—, —S—, —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,
wherein “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 the following formulae (A1-1), (A1-2), (A1-3), (A1-4), (A1-5), (A1-6), (A1-7), (A1-8), (A2-1), (A2-2), (A5-1), (A5-2), (A5-3), (A5-4), (A6-1), and (A7-1):
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,
-[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.
3. An α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof represented by the following formula (I):
wherein “A” represents optionally substituted heterocyclic diyl,
wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is selected from the group consisting of chromanediyl, 5,6,7,8-tetrahydroquinolinediyl, isoquinolinediyl, naphthyridinediyl, and 5,6,7,8-tetrahydroisoquinolinediyl,
R 1 represents hydrogen atom,
R 2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, and R 2 is not pyrimidinyl when X═NH,
X represents —O—, —S—, —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.
4. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 2 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is heterocyclic diyl selected from the group consisting of the following formulae (A1-1), (A1-2), (A1-3), (A1-4), (A1-5), (A1-6), (A1-7) and (A1-8).
5. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 3 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is 5,6,7,8-tetrahydroquinolinediyl.
6. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 2 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is heterocyclic diyl represented by the following formula (A2-1) or (A2-2).
7. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 3 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is chromanediyl.
8. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 3 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is isoquinolinediyl.
9. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 2 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is heterocyclic diyl selected from the group consisting of the following formulae (A5-1), (A5-2), (A5-3) and (A5-4).
10. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 3 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is naphthyridinediyl.
11. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 2 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is heterocyclic diyl represented by the following formula (A6-1).
12. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 3 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is 5,6,7,8-tetrahydroisoquinolinediyl.
13. The α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 2 , wherein the heterocyclic diyl in the optionally substituted heterocyclic diyl is heterocyclic diyl represented by the following formula (A7-1).
14. A pharmaceutical composition comprising the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 1 and a carrier.
15. A method for the treatment of cancer, comprising:
administrating the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 1 to a subject.
16. A pharmaceutical composition comprising the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 3 and a carrier.
17. A method for the treatment of cancer, comprising:
administrating the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 3 to a subject.
18. A pharmaceutical composition comprising the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 2 and a carrier.
19. A method for the treatment of cancer, comprising:
administrating the α,β-unsaturated amide compound or a pharmaceutically acceptable salt thereof according to claim 2 to a subject.