3,5-diaminobenzoic acid compound, and Pin1 inhibitor and therapeutic agent for inflammatory diseases using same
The present invention provides: a compound represented by the following Formula (I) or a salt thereof, as well as a Pin1 inhibitor, a pharmaceutical composition, a therapeutic or prophylactic agent for inflammatory diseases, a therapeutic or prophylactic agent for fatty liver diseases, a therapeutic or prophylactic agent for obesity, and a therapeutic or prophylactic agent for COVID-19 that utilize the aforementioned compounds or the salts thereof to develop a group of novel compounds with an inhibitory activity against the function of Pin1 so as to use them as candidate compounds for medicaments.
1 . A compound represented by Formula (I), or a salt thereof:
wherein ring A represents an optionally substituted monocyclic or polycyclic aromatic ring or heterocycle;
R 1 represents a group represented by any of the following Formulae (II) to (V):
wherein ring B represents an optionally substituted monocyclic heterocycle, Rings C and D independently represent an optionally substituted monocyclic or polycyclic aromatic ring, heterocycle or cyclic hydrocarbon, and the rings B, C and D form a condensed ring
wherein ring E represents an optionally substituted monocyclic heterocycle, ring F represents an optionally substituted monocyclic or polycyclic aromatic ring, heterocycle or cyclic hydrocarbon, and the rings E and F form a condensed ring
wherein rings G and H independently represent an optionally substituted monocyclic or polycyclic aromatic ring or heterocycle
wherein ring I represents an optionally substituted monocyclic aromatic ring or heterocycle, a ring J represents an optionally substituted monocyclic or polycyclic aromatic ring, heterocycle or cyclic hydrocarbon, the rings I and J form a condensed ring, and R6 represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group;
R 2 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted amino group;
R 3 represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group;
R 4 represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group;
R 5 represents 0 to 3 identical or different substituents attached to the benzene ring;
X represents a single bond, C 1-2 alkylene group, —O— group, —CH 2 —O group, —CH 2 —NH—CO— group, or —CH 2 —NH—CO—O—CH 2 — group; and
Y represents a single bond or C 1-2 alkylene group.
2 . The compound or the salt thereof according to claim 1 , wherein the ring A represents an optionally substituted polycyclic aromatic ring or heterocycle.
3 . The compound or the salt thereof according to claim 2 , wherein ring A represents a ring represented by Formula (VI):
wherein A 1 , A 2 , and A 3 independently represent a carbon atom or a nitrogen atom, and ring K represents an optionally substituted monocyclic or polycyclic aromatic ring, heterocycle or cyclic hydrocarbon.
4 . The compound or the salt thereof according to claim 3 , wherein all of A 1 , A 2 , and A 3 represent a carbon atom.
5 . The compound or the salt thereof according to claim 1 , wherein R 1 represents a group represented by Formula (II):
wherein ring B represents an optionally substituted monocyclic heterocycle, rings C and D independently represent an optionally substituted monocyclic or polycyclic aromatic ring, heterocycle or cyclic hydrocarbon, and the rings B, C and D form a condensed ring.
6 . The compound or the salt thereof according to claim 1 , wherein R 2 represents a hydrogen atom.
7 . The compound or the salt thereof according to claim 1 , wherein R 3 represents a hydrogen atom.
8 . The compound or the salt thereof according to claim 1 , wherein R 4 represents a hydrogen atom.
9 . The compound or the salt thereof according to claim 1 , wherein X represents a single bond.
10 . The compound or the salt thereof according to claim 1 , wherein Y represents a single bond.
11 . A Pin1 inhibitor comprising the compound or the salt thereof according to claim 1 .
12 . A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier.
13 . A method of treating or preventing an inflammatory disease, comprising administering to a subject in need thereof the compound or the pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.
14 . A method of treating or preventing an inflammatory disease, comprising administering to a subject in need thereof the compound or the pharmaceutically acceptable salt thereof according to claim 1 in combination with active ingredients in at least one or more drugs selected from a group of drugs classified as a therapeutic or prophylactic agent for the inflammatory disease.
15 . The method according to claim 13 , wherein the inflammatory disease is non-alcoholic steatohepatitis, inflammatory bowel disease, or pulmonary fibrosis.
16 . A method of treating or preventing a fatty liver disease comprising administering to a subject in need thereof the compound or the pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.
17 . A method of treating or preventing a fatty liver disease comprising administering to a subject in need thereof the compound or the pharmaceutically acceptable salt thereof according to claim 1 in combination with active ingredients in at least one or more drugs selected from a group of drugs classified as a therapeutic or prophylactic agent for the fatty liver disease.
18 . A method of treating or preventing obesity comprising administering to a subject in need thereof the compound or the pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.
19 . A method of treating of preventing obesity comprising administering to a subject in need thereof the compound or the pharmaceutically acceptable salt thereof according to claim 1 in combination with active ingredients in at least one or more drugs selected from a group of drugs classified as a therapeutic or prophylactic agent for obesity.
20 . A method of treating or preventing COVID-19 comprising administering to a subject in need thereof the compound or the pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.
21 . A method of treating or preventing COVID-19 comprising administering to a subject in need thereof the compound or the pharmaceutically acceptable salt thereof according to claim 1 in combination with active ingredients in at least one or more drugs selected from a group of drugs classified as a therapeutic or prophylactic agent for coronavirus.
22 . The method according to claim 14 , wherein the inflammatory disease is non-alcoholic steatohepatitis, inflammatory bowel disease, or pulmonary fibrosis.