Benzopyran derivatives, their preparation and pharmaceutical compositions containing them

• US 5,025,013 A
• Filed: 01/16/1990
• Issued: 06/18/1991
• Est. Priority Date: 01/20/1989
• Status: Expired due to Fees

• Current Assignee: Rhone-Poulenc Sante (Sanofi )
• Original Assignee: Rhone-Poulenc Sante (Sanofi )
• Inventors: Martin, Jean-Paul, Hardy, Jean-Claude, Barreau, Michel, Renault, Christian
• Primary Examiner(s): Shen, Cecilia
• Application Number:
  US07/465,330
• Time in Patent Office: 518 Days
• Field of Search: 544/360, 544/363, 544/364, 544/373, 544/376, 546/168, 546/174, 546/193, 546/194, 546/196, 514/253, 514/314, 514/320
• US Class Current: 514/253.06
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: C07D 311/58 other than with oxygen or sulphur atoms in position 2 or 4
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings

Abstract

New benzopyran derivatives of general formula (I) in which:

R₁ represents a hydrogen or halogen atom or a hydroxy, alkyloxy, nitro, amino, alkylsulphonamido or acylamino radical,

R represents

(1) radical ##STR1## R₂ and R₃, which may be identical or different, being H, halogen, OH, alkyl, alkyloxy, NH₂, alkylsulphonamido or NO₂, or

(2) a radical ##STR2## n being 0 or 1, R₄ being H, alkyl or optionally substituted phenyl and Q is acyl, alkylsulphonyl or ##STR3## Y being --CO-- or --SO₂ -- and Z being a single bond, --CH₂ -- or --NH--, or

(3) a radical ##STR4## n being 0 or 1, m being 0 or 2, X being C or N (if n=0), W being a bond or --NH-- and AR being pyridyl, indolyl, quinolyl, 2-alkylquinolyl or phenyl optionally substituted with R₂ and R₃, provided that n=0 when X equals N, or

(4) a radical of general formula: ##STR5## R₇ being H or alkyl, or alternatively (5) a radical ##STR6## R'"'"' and R" are identical and represent hydrogen atoms or alkyl radicals, their isomeric forms and the mixtures thereof, and their addition salts with acids.

These new products are useful as anti-arrhythmic and antifibrillating agents. ##STR7##

Claims

1. A benzopyran compound having the formula:

##STR28## wherein R₁ represents a hydrogen or halogen atom or a hydroxy, alkyloxy, nitro, amino, alkylsulphonamido or acylamino radical,

R represents

(1) a radical of formula;

##STR29## wherein R₂ and R₃, which may be identical or different, represent hydrogen or halogen atoms or hydroxy, alkyl, alkyloxy, amino, alkylsulphonamido or nitro radicals, or alternatively

(2) a radical of formula;

##STR30## wherein n equals 0 or 1, R₄ is a hydrogen atom, an alkyl radical or a radical of structure;

##STR31## wherein R₅ and R₆ are hydrogen or halogen atoms or an alkyloxy radical, and Q represents an acyl or alkylsulphonyl radical or a radical of structure;

##STR32## wherein R₂ and R₃ are defined as above, Y represents a carbonyl or sulphonyl radical and Z represents a single bond or a methylene or imino radical, or alternatively

(3) a radical of formula;

##STR33## wherein n equals 0 or 1, m equals 0 to 2, X is a carbon atom or X can be a nitrogen atom if n=0, W represents a single bond or an imino radical and Ar represents a pyridyl, indolyl, quinolyl or 2-alkylquinolyl radical or a phenyl radical optionally substituted with radicals R₂ and R₃ as defined above, provided that m is other than 0 when X is a nitrogen atom, or alternatively

(4) a radical of formula;

##STR34## wherein R₂ and R₃ are defined as above and R₇ denotes a hydrogen atom or an alkyl radical, or alternatively

(5) a radical of formula;

##STR35## and R'"'"' and R", which are identical, represent hydrogen atoms or alkyl radicals,

on the understanding that the alkyl and acyl radicals and portion mentioned above contain 1 to 4 carbon atoms in a straight or branched chain, in its isomeric forms and the mixtures thereof, as well as its pharmaceutically acceptable addition salts with acids.

2. A benzopyran compound according to claim 1, wherein R₁, R'"'"' and R" are hydrogen atoms, and R represents a radical as defined at (1) for which R₂ and R₃ are hydrogen atoms, or

R represents a radial as defined at (2) for which n equals 0, R₄ is a hydrogen atom, an alkyl radical or a radical of structure:

##STR36## in which R₅ and R₆ are hydrogen or halogen atoms or alkyloxy radicals and Q represents an acetyl or methylsulphonyl radical or a radical of formula;

##STR37## wherein Y is a carbonyl or sulphonyl radical and Z is a bond or a methylene or imino radical, and R₂ and R₃ are hydrogen or halogen atoms or alkyl or methylsulphonamido radicals, or

R represents a radical as defined at (3) for which n equals 0, m equals 0 to 2, W is a bond or an imino radical, Ar is pyridyl, indolyl or phenyl optionally substituted with a halogen atom or alkyl or alkyloxy radicals and X is a carbon or nitrogen atom, or R represents a radical as defined at (4) for which R₇ represents a hydrogen atom.

8. A pharmaceutical composition, which comprises an effective amount benzopyran compound according to claim 1, in the pure state or in the form of a combination with one or more compatible and pharmaceutically acceptable adjuvants or diluents.

3. N-{1-[2-(3,4-Dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidyl}acetanilide or a pharmaceutically acceptable salt thereof.

4. 1-[2-(3,4-Dihydro-2H-1-benzopyran-4-yl)ethyl]-4-or a pharmaceutically acceptable salt thereof.

5. N-{1-[2-(3,4-Dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidyl}-N-phenyl-4-fluorobenzamide or a pharmaceutically acceptable salt thereof.

6. 4-Benzoyl-1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]piperidine or a pharmaceutically acceptable salt thereof.

7. {1-[2-(3,4-Dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidyl}phenylmethanoxime or a pharmaceutically acceptable salt thereof.