USPA benzolyguanidines

• US 5,292,755 A
• Filed: 01/31/1992
• Issued: 03/08/1994
• Est. Priority Date: 09/06/1989
• Status: Expired due to Term

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Hoechst Aktiengesellschaft (Sanofi )
• Inventors: Englert, Heinrich C., Scholz, Wolfgang, Lang, Hans-Jochen, Linz, Wolfgang, Scholkens, Bernward
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): CHANG, CELIA C
• Application Number:
  US07/830,355
• Time in Patent Office: 767 Days
• Field of Search: 544/158, 544/159, 544/393, 544/332, 540/483, 540/610, 546/149, 546/164, 546/172, 546/193, 546/231, 548/339, 548/491, 548/563, 564/85, 564/237, 514/307, 514/311, 514/316, 514/331, 514/237.8, 514/255, 514/275, 514/400, 514/415, 514/427, 514/603, 514/634, 514/212, 514/183
• US Class Current: 514/331
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• 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: C07C 2601/06 with a five-membered ring
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 311/47 Y being a hetero atom
• CPC Class Codes: C07C 317/42 Y being a hetero atom
• CPC Class Codes: C07C 323/67 containing sulfur atoms of sulfonamide groups, bound to the carbon skeleton
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 295/155 with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/26 Sulfur atoms

Abstract

Benzoylguanidines of the formula I ##STR1## where R(1) or R(2) is equal to R(6)--S(O)_n -- or R(7)R(8)N--O₂ S--

and the other substituent R(1) or R(2) is in each case equal to H, F, Cl, Br, I, alkyl, alkoxy or phenoxy, R(6)--S(O)_n or R(7)R(8)N--

and R(6) is equal to alkyl, cycloalkyl, cyclopentylmethyl, cyclohexylmethyl or phenyl,

R(7) and R(8) are equal to alkyl or phenylalkyl or phenyl,

and in which R(7) and R(8) may also together be a C₄ --C₇ chain, and in which R(7) and R(8), together with the nitrogen atom to which they are bonded, may be a dihydroindole, tetrahydroquinoline or tetrahydroisoquinoline system,

and where R(3), R(4) and R(5) are equal to hydrogen or alkyl, or R(3) and R(4) are together an alkylene chain or R(4) and R(4) are together an alkylene chain,

and where n is equal to zero, 1 or 2

and their pharmaceutically tolerable salts are outstanding antiarrhythmics.

Claims

1. A benzoylguanidine of formula I ##STR8## in which one of R(1) and R(2) is R(6)--S(O)_n -- or ##STR9## and the other of R(1) and R(2) is H, F, Cl, Br, I, C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, phenoxy which is unsubstituted or carries one to three substituents selected from fluorine, chlorine, methyl or methoxy, R(6)--S(O)_n or ##STR10## in which R(6) is C₁ -C₆ -alkyl, C₅ -C₇ -cycloalkyl, cyclopentylmethyl, cyclohexylmethyl or phenyl which is unsubstituted or carries one to three substituents selected from fluorine, chlorine, methyl or methoxy;

R(7) and R(8) are identical or different and are H or C₁ -C₆ -alkyl;

or R(7) is phenyl-(CH₂)_m -- where m=1-4, or phenyl which is unsubstituted or carries one or two substituents selected from fluorine, chlorine, methyl or methoxy;

or

R(7) and R(8) together are a straight or branched C₄ -C₇ chain,

R(3), R(4) and R(5) are hydrogen; and

n is zero, 1 or 2;

and their pharmaceutically tolerable salts,

with the proviso that said benzoylguanidine is not 3-methylsulfonyl-4-(1-piperidinyl)benzoylguanidine, 4-phenylthio-3-sulfamoylbenzoylguanidine, or 3-methylsulfonyl-4-phenylthiobenzoylguanidine.

2. A compound I as claimed in claim 1, in which:

R(1) is fluorine, chlorine, NR(7)R(8), R(6)--S(O)_n -- or phenoxy,

R(2) is R(6)--S(O)_n -- and R(7)R(8)N--SO₂ --

and in which n is zero, 1 or 2

and R(3), R(4) and R(5) are hydrogen,

and in which R(6), R(7) and R(8) have the abovementioned meaning, and their pharmacologically tolerable salts.

3. A compound I as claimed in claim 1, in which:

R(1) is R(7)R(8)N-- or R(6)--S(O)_n --, in which R(6) is alkyl having 1-3 carbon atoms or phenyl,

n=zero

and R(7) and R(8) are hydrogen or alkyl having 1-4 carbon atoms, or R(7) and R(8) together form a (C₄ -C₇)-methylene chain and

R(2) is CH₃ --SO₂ -- or H₂ N--SO₂ --, R(3), R(4) and R(5) are hydrogen, and their pharmacologically tolerable salts.

4. A method of treating arrhythmias comprising administering to a host an effective amount for treating arrhythmias of compound I according to claim 1.