8-hydroxyquinoline compound and use thereof
AssigneeOsaka University
InventorsOsamu TSUKAMOTO, Seiji TAKASHIMA, Junichi HARUTA, Toshio KANAI
Life of this patent
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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 R1 represents hydrogen or the like; R2 represents R7CO— (R7 is C1-6 alkyl or the like) or the like; R3 represents hydrogen; and R4, R5, and R6 represent hydrogen or the like.
Claims9
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
- R1 represents hydrogen, aryl, a heterocyclic group, C1-6 alkyl optionally substituted with aryl, C3-8 cycloalkyl, C2-6 alkenyl optionally substituted with aryl or heteroaryl, C3-8 cycloalkenyl, or C2-6 alkynyl optionally substituted with aryl;
- R2 represents hydrogen, R7CO—, or heteroaryl;
- R3 represents hydrogen;
- wherein R7 represents hydrogen, C1-6 alkyl optionally substituted with aryl or heteroaryl, C1-6 alkylamino, C3-8 cycloalkyl that may contain oxygen in a cycloalkyl ring, C3-8 cycloalkylamino, C1-6 alkoxy optionally substituted with aryl, C3-8 cycloalkoxy, C1-3 alkoxy-C1-3 alkyl, C1-4 alkoxycarbonyl C1-4 alkyl, aryl, aryloxy, pyridyl, or amino;
- R1 and R2, taken together with the nitrogen to which they are attached, may form an oxindole ring;
- and
- R2 and R3, taken together with the nitrogen to which they are attached, via —CH2CH2X (R8) CH2CH2—, may form a ring, wherein X represents —CH or nitrogen, and R8 represents hydrogen, aryl C1-6 alkyl, or aryl C1-6 alkoxycarbonyl;
- R4 represents hydrogen, C1-6 alkyl, or halogen;
- R5 represents hydrogen, nitro, halogen, or sulfonyl;
- and
- R6 represents hydrogen or C1-6 alkyl.
2-7. (canceled)
An 8-hydroxyquinoline compound represented by the following formula (Ia) or a pharmaceutically acceptable salt thereof, or a solvate thereof,
- wherein
- R1a represents hydrogen, aryl, a heterocyclic group, aryl C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl optionally substituted with aryl or heteroaryl, C3-8 cycloalkenyl, or aryl C2-6 alkynyl;
- R2a represents R7a CO— or thiazolyl;
- R3a represents hydrogen;
- wherein R7a represents hydrogen, C1-6 alkyl optionally substituted with aryl or heteroaryl, C1-6 alkylamino, C3-8 cycloalkyl that may contain oxygen in a cycloalkyl ring, C3-8 cycloalkylamino, C1-6 alkoxy optionally substituted with aryl, C3-8 cycloalkoxy, C1-3 alkoxy-C1-3 alkyl, C1-4 alkoxycarbonyl C1-4 alkyl, aryloxy, pyridyl, or amino;
- R1a and R2a, taken together with the nitrogen to which they are attached, may form an oxindole ring;
- and
- R2a and R3a, taken together with the nitrogen to which they are attached, via —CH2CH2X (R8) CH2CH2—, may form a ring, wherein X represents nitrogen, and R8 represents aryl C1-6 alkoxycarbonyl;
- R4a represents hydrogen, C1-6 alkyl, or halogen;
- R5a represents hydrogen, nitro, halogen, or sulfonyl;
- and
- R6a represents hydrogen or C1-6 alkyl.
Dependencies are inferred from the claim text.