4-quinolinone derivative or salt thereof

• US 5,789,419 A
• Filed: 12/09/1996
• Issued: 08/04/1998
• Est. Priority Date: 06/09/1994
• Status: Expired due to Fees

• Current Assignee: SS Pharmaceutical Company Limited
• Original Assignee: SS Pharmaceutical Company Limited
• Inventors: Kuraishi, Tadayuki, Yamazaki, Kazuo, Matsuda, Hideaki, Adegawa, Shigeru, Ogawa, Yoichiro
• Primary Examiner(s): Rotman, Alan L.
• Assistant Examiner(s): SEAMAN, D MARGARET M
• Application Number:
  US08/750,146
• Time in Patent Office: 603 Days
• Field of Search: 514/312, 516/153, 516/159
• US Class Current: 514/312
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 215/58 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links

Abstract

This invention relates to a 4-quinolinone derivative represented by the following general formula (1): ##STR1## wherein R¹ and R² mean individually H, halogen, cyano, or lower alkyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio or lower alkoxy which may be substituted by halogen, or phenylsulfonyl, phenylsulfinyl or phenylthio which may have a substituent; and R³ and R⁴ denote individually H, lower alkyl or cycloalkyl which may be substituted by halogen, or pyridyl, furanyl or phenyl which may have a substituent, or R³ and R⁴ may form a 4-, 5- or 6-membered heterocyclic ring, or a salt thereof, and an intermediate useful for the preparation thereof, and besides a medicinal composition comprising this compound as an active ingredient. The compound (1) or the salt thereof has an excellent potassium channel-activating effect and is useful as, for example, a prophylactic and therapeutic agent for diseases of circulatory and bronchial systems.

Claims

1. A 4-quinolinone derivative represented by the following general formula (1):

##STR77## wherein R¹ and R² may be the same or different from each other and mean individually a hydrogen atom;

a halogen atom;

a cyano group;

a lower alkyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio or lower alkoxy group which may be substituted by halogen atom;

or a phenylsulfonyl, phenylsulfinyl or phenylthio group which may have a substituent; and

R³ and R⁴ may be the same or different from each other and denote individually a hydrogen atom;

a lower alkyl or cycloalkyl group which may be substituted by halogen atom;

or a pyridyl, furanyl or phenyl group which may have a substituent, or R³ and R⁴ may form a 4-, 5- or 6-membered heterocyclic ring, which may be substituted by a lower alkyl group, together with the adjacent carbon atom and nitrogen atom, or a salt thereof.

2. The 4-quinolinone derivative or the salt thereof according to claim 1, wherein R¹ and R² may be the same or different from each other and mean individually a hydrogen atom;

a halogen atom;

a cyano group;

an alkyl, alkylsulfonyl, alkylsulfinyl, alkylthio or alkoxy group which has 1-6 carbon atoms and may be substituted by 1-3 halogen atoms;

a phenylsulfonyl group;

a phenylsulfinyl group;

or a phenylthio group; and

R³ and R⁴ may be the same or different from each other and denote individually a hydrogen atom;

an alkyl group having 1-6 carbon atoms or a cycloalkyl group having 3-6 carbon atoms, which may be substituted by 1-3 halogen atoms;

or a pyridyl, furanyl or phenyl group which may be substituted by a substituent selected from a halogen atom, a hydroxyl group, an alkoxy group having 1-6 carbon atoms, an aryloxy group, an aralkyloxy group, a nitroxy group, an amino group, a cyano group, a nitro group, an alkylamino group having 1-6 carbon atoms, a dialkylamino group having 2-12 carbon atoms, a cyclic amino group, an aryl group, an aminosulfonyl group or an alkyl group having 1-6 carbon atoms, or R³ and R⁴ may form a 2-oxoazetidinyl, 2-oxopyrrolidinyl or 2-oxopiperidinyl group, which may be substituted by an alkyl group having 1-6 carbon atoms, together with the adjacent carbon atom and nitrogen atom.

5. A medicinal composition comprising the 4-quinolinone derivative or the salt thereof according to claim 1 and a pharmaceutically acceptable carrier for medicines.

6. The medicinal composition according to claim 5, which is suitable for use in treating a disease of circulatory or bronchial system.

7. The medicinal composition according to claim 5, which is suitable for use in treating an ischemic heart disease, hypertension or bronchial asthma.

8. A method of treating a disease of the circulatory or bronchial system, comprising administering to a patient in need thereof an effective amount of the 4-quinolinone derivative or salt thereof according to claim 1.

9. The method of claim 8, wherein said disease is ischemic heart disease, hypertension or bronchial asthma.

3. An N-amino-4-quinolinone derivative represented by the following general formula (2):

##STR78## wherein R¹ and R² may be the same or different from each other and mean individually a hydrogen atom;

a halogen atom;

a cyano group;

a lower alkyl, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio or lower alkoxy group which may be substituted by halogen atom;

or a phenylsulfonyl, phenylsulfinyl or phenylthio group which may have a substituent, or a salt thereof.

4. The N-amino-4-quinolinone derivative or the salt thereof according to claim 3, wherein R¹ and R² may be the same or different from each other and mean individually a hydrogen atom;

a halogen atom;

a cyano group;

an alkyl, alkylsulfonyl, alkylsulfinyl, alkylthio or alkoxy group which has 1-6 carbon atoms and may be substituted by 1-3 halogen atoms;

a phenylsulfonyl group;

a phenylsulfinyl group;

or a phenylthio group.