Phenyl-substituted alkylcarboguanidides carrying perfluoroalkyl groups, a process for their preparation, their use as a medicament or a diagnostic agent, and a medicament containing them

• US 5,567,734 A
• Filed: 01/23/1995
• Issued: 10/22/1996
• Est. Priority Date: 01/25/1994
• Status: Expired due to Term

• Current Assignee: Hoechst Aktiengesellschaft (Sanofi )
• Original Assignee: Hoechst Aktiengesellschaft (Sanofi )
• Inventors: Scholz, Wolfgang, Lang, Hans-Jochen, Kleemann, Heinz-Werner, Weichert, Andreas, Schwark, Jan-Robert, Albus, Udo
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US08/377,012
• Time in Patent Office: 638 Days
• Field of Search: 564/147, 564/161, 564/163, 564/164, 564/165, 514/614, 514/615, 514/617, 514/619, 514/620, 514/622, 558/414
• US Class Current: 514/617
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A61B 10/00 Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis vaccination prophylaxis, vaccination therapy A61B17/20; Sex determination; Ovulation-period determination menstruation tables G06C3/00; Throat striking implements
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: A61P 9/12 Antihypertensives
• CPC Class Codes: C07C 279/22 Y being a hydrogen or a carbon atom, e.g. benzoylguanidines
• CPC Class Codes: C07D 241/26 with nitrogen atoms directly attached to ring carbon atoms

Abstract

Phenyl-substituted alkylcarboguanidides carrying perfluoroalkyl groups, of the formula I ##STR1## are described where R(A) and R(B) are H, Hal, CN, OR(6), alkyl, O_r -perfluoroalkyl or NR(7)R(8); R(6) is hydrogen, (cyclo)alk(en)yl, perfluoroalkyl, phenyl or benzyl; R(7) and R(8) are defined as R(6); X is 1-3; R(1) is H, alkyl or --O_0-1 (CH₂)O_0-1 perfluoroalkyl; R(2), R(3), R(4) and R(5) are defined as R(1), with the condition, however, that R(1), R(2), R(3), R(4) and R(5) are not simultaneously hydrogen and that R(1), R(2), R(3), R(4) and R(5) can only be alkyl when at least one of the substituents R(A) or R(B) contains a O_r (CH₂)_a C_b F_2b+1 group; as are the pharmaceutically acceptable salts thereof. Methods of preparation of compounds of formula I are also described.

Claims

1. A phenyl-substituted alkylcarboguanidide, carrying at least one perfluoroalkyl group, of the formula I ##STR5## in which:

R(A) is hydrogen, F, Cl, Br, I, CN, OR(6), (C₁ -C₄)-alkyl, --C_b F_2b+1 or NR(7)R(8);

b is 1, 2, 3, or 4;

R(6) is hydrogen, (C₁ -C₄)-alkyl, (C₁ -C₄)-perfluoroalkyl, phenyl or benzyl, where the aromatic radicals are unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF₃, methyl, methoxy and NR(9)(10), R(9) and R(10) are H, CH₃ or CF₃ ;

R(7) and R(8) are, independently of each other, defined as R(6);

R(B) is, independently, defined as R(A);

X is 2;

R(1) is hydrogen, (C₁ -C₄)-alkyl, --C_e F_2e+1, F, or Cl;

e is 1, 2, 3, or 4;

R(2), R(3), R(4) end R(5) are, independently of each other, defined as R(1), with the condition, however, that at least one of the substituents R(1), R(2), R(3), R(4), R(5), R(A) and R(B) is a --C_e F_2e+1 or a --C_b F_2b+1 group, or a pharmaceutically tolerated salt thereof.

2. A pharmaceutical composition for treating (1) cardiac infarct, (2) angina pectoris, (3) arrhythmia, (4) a disease caused by ischemic conditions, (5) a shock condition, or (6) a disease in which cell proliferation is a primary or secondary cause;

for inhibiting the Na+/H+ exchanger;

for diagnosing hypertension, atherosclerosis, diabetes or a proliferative disease;

for use in a surgical operation or organ transplant;

or for use in preserving and storing a transplant for surgical procedure, which comprises an effective amount of a compound of formula I or a salt thereof as claimed in claim 1 together with a pharmaceutically acceptable carrier.

3. A method of treating or preventing a disease caused by ischemic conditions, which comprises administering to a host in need of said treatment an effective amount of a compound of formula I or a salt thereof as claimed in claim 1.