Ester compound and PIN1 inhibitor, inflammatory disease therapeutic, and colon cancer therapeutic in which said ester compound is used
An object of the present invention is to develop a therapeutic agent for an inflammatory disease such as an inflammatory bowel disease or NASH, which therapeutic agent shows less side effects and high effectiveness. The present invention provides a compound represented by Formula (I) or a salt thereof; and a Pin1 inhibitor, a pharmaceutical composition, a therapeutic agent or a prophylactic agent for an inflammatory disease, and a therapeutic agent or a prophylactic agent for colon cancer, containing the compound.
1. A compound represented by Formula (I):
wherein
m represents an integer of 1 to 3, and n represents an integer of 0 to 2, with the proviso that 1≤m+n≤3;
R 1 represents a hydrogen atom, a hydrocarbon group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), or an amino group optionally having a substituent(s);
R 2 represents a polycyclic aryl group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), an aryloxy group optionally having a substituent(s), a phenyl group having a substituent(s), an aralkyl group having a substituent(s), or a group represented by the following Formula (II):
wherein Ring A and Ring B each represent a monocyclic or polycyclic aryl group or heterocyclic group optionally having a substituent(s); R 4 represents a single bond, a C 1-3 alkylene group optionally having a substituent(s), a C 2-3 alkenylene group optionally having a substituent(s), or a divalent oxy group; and the Ring A, Ring B, or R 4 moiety is linked to X;
R 3 represents 0 to 7 substituent(s) linked to the naphthyl group, each of which substituent(s) is the same or different and has 1 to 10 atoms; and
X represents:
(i) a single bond;
(ii) a C 1-6 alkylene group optionally having a substituent(s);
(iii) a C 2-6 alkenylene group optionally having a substituent(s);
(iv) an —R 5 —NH— group or an —NH—R 5 — group, wherein R 5 represents a C 1-5 alkylene group optionally having a substituent(s), or a C 2-5 alkenylene group optionally having a substituent(s); or
(v) a secondary or tertiary amino group;
or a salt thereof.
2. The compound or the salt thereof according to claim 1 , wherein the R 1 represents a hydrogen atom.
3. The compound or the salt thereof according to claim 1 , wherein the R 2 represents a polycyclic aryl group optionally having a substituent(s), a polycyclic heterocyclic group optionally having a substituent(s), a polycyclic aryloxy group optionally having a substituent(s), or a group represented by the following Formula (II):
wherein Ring A and Ring B each represent a monocyclic or polycyclic aryl group optionally having a substituent(s); R 4 represents a C 1-3 alkylene group optionally having a substituent(s), a C 2-3 alkenylene group optionally having a substituent(s), or a divalent oxy group; and the Ring A, Ring B, or R 4 moiety is linked to X.
4. The compound or the salt thereof according to claim 3 , wherein the R 2 represents a polycyclic aryl group optionally having a substituent(s), a heterocyclic group containing two or more benzene rings and optionally having a substituent(s), or a polycyclic aryloxy group optionally having a substituent(s).
5. The compound or the salt thereof according to claim 1 , wherein the configuration at the asymmetric carbon atom indicated by the symbol “*” is the R configuration.
6. A Pin1 inhibitor comprising the compound or the salt thereof according to claim 1 .
7. A pharmaceutical composition comprising: the compound according to claim 1 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
8. A therapeutic agent for the treatment of an inflammatory disease accompanied by fibrosis, comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof as an effective component.
9. The therapeutic agent according to claim 8 , wherein the inflammatory disease accompanied by fibrosis is an inflammatory bowel disease, non-alcoholic steatohepatitis, or pulmonary fibrosis.
10. The therapeutic agent according to claim 8 , wherein the inflammatory disease accompanied by fibrosis is an inflammatory bowel disease.
11. The therapeutic agent according to claim 10 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
12. A therapeutic agent for the treatment of colon cancer, comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof as an effective component.
13. A method of treating an inflammatory disease accompanied by fibrosis, comprising administering the compound according to claim 1 to a patient.
14. A method of treating colon cancer, comprising administering the compound according to claim 1 to a patient.
15. A method for treating an inflammatory disease accompanied by fibrosis, wherein said method comprises administering to a subject in need thereof a therapeutic amount of a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof:
wherein
m represents an integer of 0 to 3, and n represents an integer of 0 to 2, with the proviso that 1<m+n<3;
R 1 represents a hydrogen atom, a hydrocarbon group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), or an amino group optionally having a substituent(s);
R 2 represents a polycyclic aryl group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), an aryloxy group optionally having a substituent(s), a phenyl group having a substituent(s), an aralkyl group having a substituent(s), or a group represented by the following Formula (II):
wherein Ring A and Ring B each represent a monocyclic or polycyclic aryl group or heterocyclic group optionally having a substituent(s); R 4 represents a single bond, a C 1-3 alkylene group optionally having a substituent(s), a C 2-3 alkenylene group optionally having a substituent(s), or a divalent oxy group; and the Ring A, Ring B, or R 4 moiety is linked to X;
R 3 represents 0 to 7 substituent(s) linked to the naphthyl group, each of which substituent(s) is the same or different and has 1 to 10 atoms; and
X represents:
(i) a single bond;
(ii) a C 1-6 alkylene group optionally having a substituent(s);
(iii) a C 2-6 alkenylene group optionally having a substituent(s);
(iv) an —R 5 —NH— group or an —NH—R 5 — group, wherein R 5 represents a C 1-5 alkylene group optionally having a substituent(s), or a C 2-5 alkenylene group optionally having a substituent(s); or
(v) a secondary or tertiary amino group.
16. A method for treating colon cancer, wherein said method comprises administering to a subject in need thereof a therapeutic amount of a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof:
wherein
m represents an integer of 0 to 3, and n represents an integer of 0 to 2, with the proviso that 1<m+n<3;
R 1 represents a hydrogen atom, a hydrocarbon group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), or an amino group optionally having a substituent(s);
R 2 represents a polycyclic aryl group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), an aryloxy group optionally having a substituent(s), a phenyl group having a substituent(s), an aralkyl group having a substituent(s), or a group represented by the following Formula (II):
wherein Ring A and Ring B each represent a monocyclic or polycyclic aryl group or heterocyclic group optionally having a substituent(s); R 4 represents a single bond, a C 1-3 alkylene group optionally having a substituent(s), a C 2-3 alkenylene group optionally having a substituent(s), or a divalent oxy group; and the Ring A, Ring B, or R 4 moiety is linked to X;
R 3 represents 0 to 7 substituent(s) linked to the naphthyl group, each of which substituent(s) is the same or different and has 1 to 10 atoms; and
X represents:
(i) a single bond;
(ii) a C 1-6 alkylene group optionally having a substituent(s);
(iii) a C 2-6 alkenylene group optionally having a substituent(s);
(iv) an —R 5 —NH— group or an —NH—R 5 — group, wherein R 5 represents a C 1-5 alkylene group optionally having a substituent(s), or a C 2-5 alkenylene group optionally having a substituent(s); or
(v) a secondary or tertiary amino group.
17. A method for preparing a pharmaceutical for the treatment of an inflammatory disease accompanied by fibrosis, wherein said method comprises combining a pharmaceutically acceptable carrier and a therapeutic amount of a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof:
wherein
m represents an integer of 0 to 3, and n represents an integer of 0 to 2, with the proviso that 1<m+n<3;
R 1 represents a hydrogen atom, a hydrocarbon group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), or an amino group optionally having a substituent(s);
R 2 represents a polycyclic aryl group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), an aryloxy group optionally having a substituent(s), a phenyl group having a substituent(s), an aralkyl group having a substituent(s), or a group represented by the following Formula (II):
wherein Ring A and Ring B each represent a monocyclic or polycyclic aryl group or heterocyclic group optionally having a substituent(s); R 4 represents a single bond, a C 1-3 alkylene group optionally having a substituent(s), a C 2-3 alkenylene group optionally having a substituent(s), or a divalent oxy group; and the Ring A, Ring B, or R 4 moiety is linked to X;
R 3 represents 0 to 7 substituent(s) linked to the naphthyl group, each of which substituent(s) is the same or different and has 1 to 10 atoms; and
X represents:
(i) a single bond;
(ii) a C 1-6 alkylene group optionally having a substituent(s);
(iii) a C 2-6 alkenylene group optionally having a substituent(s);
(iv) an —R 5 —NH— group or an —NH—R 5 — group, wherein R 5 represents a C 1-5 alkylene group optionally having a substituent(s), or a C 2-5 alkenylene group optionally having a substituent(s); or
(v) a secondary or tertiary amino group.
18. A method for preparing a pharmaceutical for the treatment of colon cancer, wherein said method comprises combining a pharmaceutically acceptable carrier and a therapeutic amount of a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof:
wherein
m represents an integer of 0 to 3, and n represents an integer of 0 to 2, with the proviso that 1<m+n<3;
R 1 represents a hydrogen atom, a hydrocarbon group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), or an amino group optionally having a substituent(s);
R 2 represents a polycyclic aryl group optionally having a substituent(s), a heterocyclic group optionally having a substituent(s), an aryloxy group optionally having a substituent(s), a phenyl group having a substituent(s), an aralkyl group having a substituent(s), or a group represented by the following Formula (II):
wherein Ring A and Ring B each represent a monocyclic or polycyclic aryl group or heterocyclic group optionally having a substituent(s); R 4 represents a single bond, a C 1-3 alkylene group optionally having a substituent(s), a C 2-3 alkenylene group optionally having a substituent(s), or a divalent oxy group; and the Ring A, Ring B, or R 4 moiety is linked to X;
R 3 represents 0 to 7 substituent(s) linked to the naphthyl group, each of which substituent(s) is the same or different and has 1 to 10 atoms; and
X represents:
(i) a single bond;
(ii) a C 1-6 alkylene group optionally having a substituent(s);
(iii) a C 2-6 alkenylene group optionally having a substituent(s);
(iv) an —R 5 —NH— group or an —NH—R 5 — group, wherein R 5 represents a C 1-5 alkylene group optionally having a substituent(s), or a C 2-5 alkenylene group optionally having a substituent(s); or
(v) a secondary or tertiary amino group.