8-hydroxyquinoline compound and use thereof

{
  "publication_number": "US2026103444A1",
  "country": "US",
  "kind": "A1",
  "title": "8-hydroxyquinoline compound and use thereof",
  "abstract": "An object of the present invention is to provide a cMLCK activator that can enhance myocardial contractility without an increase in cellular calcium concentration. This object is achieved by a cMLCK activator containing an 8-hydroxyquinoline compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein R 1 represents hydrogen or the like; R 2 represents R 7 CO - (R 7 is C 1-6 alkyl or the like) or the like; R 3 represents hydrogen; and R 4, R 5, and R 6 represent hydrogen or the like.",
  "claims": [
    "1. A method for activating cMLCK, the method comprising administering an 8-hydroxyquinoline compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, or a solvate thereof to a subject in need of activation of cMLCK, or causing a subject in need of activation of cMLCK to ingest an 8-hydroxyquinoline compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein R 1 represents hydrogen, aryl, a heterocyclic group, C 1-6 alkyl optionally substituted with aryl, C 3-8 cycloalkyl, C 2-6 alkenyl optionally substituted with aryl or heteroaryl, C 3-8 cycloalkenyl, or C 2-6 alkynyl optionally substituted with aryl; R 2 represents hydrogen, R 7 CO -, or heteroaryl; R 3 represents hydrogen; wherein R 7 represents hydrogen, C 1-6 alkyl optionally substituted with aryl or heteroaryl, C 1-6 alkylamino, C 3-8 cycloalkyl that may contain oxygen in a cycloalkyl ring, C 3-8 cycloalkylamino, C 1-6 alkoxy optionally substituted with aryl, C 3-8 cycloalkoxy, C 1-3 alkoxy-C 1-3 alkyl, C 1-4 alkoxycarbonyl C 1-4 alkyl, aryl, aryloxy, pyridyl, or amino; R 1 and R 2, taken together with the nitrogen to which they are attached, may form an oxindole ring; and R 2 and R 3, taken together with the nitrogen to which they are attached, via - CH 2 CH 2 X (R 8) CH 2 CH 2 -, may form a ring, wherein X represents - CH or nitrogen, and R 8 represents hydrogen, aryl C 1-6 alkyl, or aryl C 1-6 alkoxycarbonyl; R 4 represents hydrogen, C 1-6 alkyl, or halogen; R 5 represents hydrogen, nitro, halogen, or sulfonyl; and R 6 represents hydrogen or C 1-6 alkyl. 2 - 7. (canceled) 8. An 8-hydroxyquinoline compound represented by the following formula (Ia) or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein R 1a represents hydrogen, aryl, a heterocyclic group, aryl C 1-6 alkyl, C 3-8 cycloalkyl, C 2-6 alkenyl optionally substituted with aryl or heteroaryl, C 3-8 cycloalkenyl, or aryl C 2-6 alkynyl; R 2a represents R 7a CO - or thiazolyl; R 3a represents hydrogen; wherein R 7a represents hydrogen, C 1-6 alkyl optionally substituted with aryl or heteroaryl, C 1-6 alkylamino, C 3-8 cycloalkyl that may contain oxygen in a cycloalkyl ring, C 3-8 cycloalkylamino, C 1-6 alkoxy optionally substituted with aryl, C 3-8 cycloalkoxy, C 1-3 alkoxy-C 1-3 alkyl, C 1-4 alkoxycarbonyl C 1-4 alkyl, aryloxy, pyridyl, or amino; R 1a and R 2a, taken together with the nitrogen to which they are attached, may form an oxindole ring; and R 2a and R 3a, taken together with the nitrogen to which they are attached, via - CH 2 CH 2 X (R 8) CH 2 CH 2 -, may form a ring, wherein X represents nitrogen, and R 8 represents aryl C 1-6 alkoxycarbonyl; R 4a represents hydrogen, C 1-6 alkyl, or halogen; R 5a represents hydrogen, nitro, halogen, or sulfonyl; and R 6a represents hydrogen or C 1-6 alkyl. 9. A method for treating heart disease, the method comprising administering the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1 to a subject with heart disease or causing a subject with heart disease to ingest the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1. 10. A method for treating heart failure, the method comprising administering the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1 to a subject with heart failure or causing a subject with heart failure to ingest the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1. 11. An inotropic agent method comprising administering the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1 to a subject in need of inotropic support or causing a subject in need of inotropic support to ingest the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1. 12. A method for enhancing myocardial contractility, the method comprising administering the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1 to a subject in need of enhancement of myocardial contractility or causing a subject in need of enhancement of myocardial contractility to ingest the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1. 13. A method for improving cardiac function, the method comprising administering the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1 to a subject in need of improvement of cardiac function or causing a subject in need of improvement of cardiac function to ingest the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1. 14. A method for use in promoting organization of a sarcomere structure, the method comprising administering the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1 to a subject in need of promotion of organization of a sarcomere structure or causing a subject in need of promotion of organization of a sarcomere structure to ingest the 8-hydroxyquinoline compound or a pharmaceutically acceptable salt thereof, or a solvate thereof of claim 1."
  ],
  "cpc": [
    "C07D 215/28",
    "A61K 31/47",
    "A61K 31/4709",
    "A61K 31/4745",
    "A61K 31/506",
    "A61K 31/5377",
    "A61K 31/55",
    "A61P 9/04",
    "C07D 215/26",
    "C07D 401/04",
    "C07D 401/06",
    "C07D 401/10",
    "C07D 401/12",
    "C07D 401/14",
    "C07D 405/06",
    "C07D 405/12",
    "C07D 413/14",
    "C07D 417/10",
    "C07D 417/12",
    "C07D 455/04",
    "C07D 471/04",
    "C07D 498/08"
  ],
  "filing_date": "2023-10-05",
  "publication_date": "2026-04-16",
  "priority_date": "2022-10-07",
  "application_number": "US-202319116786-A"
}