Acylamide compounds having secretagogue or inducer activity of adiponectin
AssigneeAjinomoto Co., Inc.
InventorsKatsumi MAEZONO, Toshihiko YOSHIMURA, Nozomu ISHIDA, Naoyuki FUKUCHI, Toshihiro HATANAKA, Osamu IKEHARA, Yayoi KAWATO, Hideyuki TANAKA
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Abstract
The present invention provides acylamide compounds, prodrugs thereof, or pharmaceutically acceptable salts thereof; and an adiponectin inducer or secretagogue, and therapeutic methods by administering the same.
Claims35
A method of treating a metabolic syndrome in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method of treating hyperlipemia in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method of treating diabetes in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method for improving glucose tolerance in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method of improving insulin resistance or enhancing insulin sensitivity in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method of treating hypertension in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method of treating a disorder selected from the group consisting of hepatic inflammation, fatty liver, hepatic fibrosis and liver cirrhosis in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method of treating non-alcoholic/nonviral steatohepatitis (NASH) or non-alcoholic/nonviral fatty liver disease (NAFLD) in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method of treating obesity in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
A method of treating hypoadiponectinemia in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of an acylamide compound, or pharmaceutically acceptable salt thereof, of the formula (1):
- wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
- R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, heteroaryl group having 1 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, heteroarylalkyl group having 2 to 11 carbon atoms or alkylthioalkyl group having 2 to 6 carbon atoms;
- R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
- R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
- R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s);
- and
- X is an oxygen atom or NH.
Dependencies are inferred from the claim text.