Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
  • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
  • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
  • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/06—Antiarrhythmics
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
  • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

• Novel sulfonamides a processes for their preparation and pharmaceutical compositions containing these new sulfonamides
• the present invention relates to novel 2-phthalimidoethanesulfone-N-arylamides. These novel compounds are represented by formula I
• R 1 is hydrogen or an alkyl or hydroxyalkyl group having
• R 2 is a)
• R 3 and R 4 can be similar or different and mean hydrogen, an alkoxy, carbalkoxy or alkyl group with 1 - 4 carbon atoms, halogen, trifluoromethyl or a nitrogroup or a group of the formula
• R 1 , R 3 and R 4 cannot at the same time mean hydrogen atoms, b )
• Z 0 , N or S .
• R 3 is hydrogen, an alkoxy, alkoxycarbonyl or alkyl group comprising 1 - 4 carbon atoms, halogen, trifluoromethyl or a nitro group or a group of the formula
• R 5 and R 6 can independently of each other mean hydrogen or an alkyl group with 1 - 4 carbon atoms
• R 4 is hydrogen or halogen.
• R 2 is hydrogen or metyl or hydroxyethyl
• R 3 is a methoxy, metoxylcarbonyl or methyl, Cl, F, trifluoromethyl or a nitrogroup or a group of the formula
• R 5 and R 6 each are hydrogen or methyl
• R 4 is hydrogen or chlorine.
• the present invention relates also to the process for preparing these novel compounds.
• the process is characterized in that
• n, R 1 and R 2 are the same as above.
• R 1 is the same as above, is alkylated with a suitable alkylating agent containing the group -(CH 2 ) n -R 2 , wherein n and R 2 are the same as above,
• n and R 2 are the same as above, is alkylated with a suitable alkylating agent containing the group R 1 defined above,
• n, R 1 and R 2 are the same as above and X is an interchangeable group such as e.g. halogen, or
• n, R 1 and R 2 are the same as above.
• the Finnish patent publication FI 67214 describes certain taurinealkylamide derivatives and their antiepileptic properties It was now surprisingly been found that the corresponding aryl derivative possesses antiarrhythmic properties.
• the antiarrhythmic effect of the compounds was studied in vitro on a spontaneously beating rat atrium preparation when arrhythmi was induced by aconitine (Holland W.C. & Burn J.H., Br. Med. J., vol. 1, 1031, 1958) as well as in situ by the raising fibrillation level electrically induced in a cat heart (Szekeres L & Papp JGy, Handbook of Experimental Pharmacology, vol. XVI/3, 131, 1975).
• Table I The effects of the seven compounds found most effective in the in vitro test compared to quinidine and lidocaine are shown in table I. In the in vitro test 20 compounds were more effective than quinidine.
• test compounds The effect of test compounds on arrhythmia induced by aconitine in a spontaneously beating atrium preparation of a rat heart and the ability to raise the fibrillation level of electrical stimulation in situ in the atrium and ventricle of a cat heart.
• Table 1 The effect of test compounds on arrhythmia induced by aconitine in a spontaneously beating atrium preparation of a rat heart and the ability to raise the fibrillation level of electrical stimulation in situ in the atrium and ventricle of a cat heart.
• Dogs (10 - 20 kg) of both sexes were anaesthetized with Nembutal (35 mg/kg i.v.).
• the test animals were breathing spontaneously and their chests were not incised.
• the pressure in the left ventricle was measured with a catheter led into the heart through the arteria carotis.
• the maximun rate of increase (dP/dt max ) of pressure in the left ventricle was used as indication of the contraction of the heart.
• the systemic blood pressure was measured from the arteria femoralis using a pressure sensor.
• test compound (0.5 - 6 mg/kg i.v.) brought about a significant increase in contration without affecting heart frequency.
• test compound 0.5 - 6 mg/kg i.v.
• mexilethine brought about a statistically significant decrease in the contraction of the heart, frequency and blood pressure with the same concentrations (table 3).
• Example 1 The compounds according to the invention can be prepared according to the following examples.
• Example 1 The compounds according to the invention.
• This compound has prepared in accordance with example 1 from 4-methylbenzylamine. The yield was 1,9 g (53 %; theor. 3.6 g). m.p. : 150 - 151°C.
• the compound was prepared in accordance with example 1 from 4-nitrobenzylamine.
• the yield was 2.7 g (69 %; theor. 3.9 g).
• m.p. 197 - 199°C.
• the compound was prepared in accordance with example 1 from furfurylamine.
• the yield was 2.7 g (81 %; theor. 3.34 g) m.p. : 134 - 136°C
• the compound was prepared in accordance with example 1 from methyl-4-aminomethylbenzoate. Yield: 3.0 g (75 %; theor. 4.02 g) m.p.: 172 - 174°C.
• the compound was prepared in accordance with example 1 from N-benzylethanolamine. Yield: 2.0 g (52 %; theor. 3.9 g) m.p.: 92 - 94°C.
• the compound was prepared in accordance with example 1 from 4-aminomethylbenzamide. Yield: 2.3 g (58 %; theor. 3.9 g) m.p. t 173 - 174°C.
• the compound was prepared in accordance with example 1 from 2,4-dichlorobenzylamide. Yield: 2.9 g (71 %; theor. 4.1 g) m.p. : 161 - 163°C.
• the compound was prepared in accordance with example 1 from 3-trifluoromethylbenzylamine. Yield: 3.24 g (79 %; theor. 4.1 g) m.p.: 134 - 135°C.
• the compound was prepared in accordance with example 1 from 4-fluorobenzylamine. Yield: 2.9 g (81 %; theor. 3.6 g) m.p.: 163 - 164°C.
• the compound was prepared in accordance with example 1 from 3-phenylpropylamine. Yield 3.0 g (81 %; theor. 3.7 g) m.p.: 117 - 119°C.
• the compound was prepared in accordance with example 1 from N,N-dimethyl-4-(2-aminoethyl)benzenesulfonamide. Yield: 2.3 g (49 %; theor. 4.65 g) m.p. ⁇ 110 - 114°C.
• the compound was prepared in accordance with example 1 from 2-(3-dimethylaminophenyl)ethylamine. Yield: 1.5 g (37 %; theor. 4.0 g) m.p.: 86 - 90°C.
• the compound was prepared in accordance with example 1 from 3-(4-dimethylaminophenyl)propylamine. Yield: 1.8 g (43 %; theor. 4.15 g) m.p.: 90 - 94°C.
• the product was crystallized form aqueous ethanol.
• the yield was 1.9 g (51 %; theor. 3.7 g).
• the melting point of the product was equal to that given in example 1.

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• 1987
  • 1987-04-10 SE SE8701524A patent/SE458606B/sv not_active IP Right Cessation
• 1988
  • 1988-03-29 AU AU14994/88A patent/AU1499488A/en not_active Abandoned
  • 1988-03-29 WO PCT/FI1988/000043 patent/WO1988007991A1/en not_active Application Discontinuation
  • 1988-03-29 JP JP63502909A patent/JPH02502996A/ja active Pending
  • 1988-03-29 EP EP88902862A patent/EP0355098A1/en not_active Withdrawn

Non-Patent Citations (1)

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