Preparations of ω-Aminosubstituted-acetamidodiphenyl Ether Perivatives and Their Pharmacological Actions

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Other Title
  • ω-Aminosubstituted-acetamidodiphenyl Ether誘導体の合成とその薬用作用
  • オメガ Aminosubstituted acetamidodiphenyl
  • Preparations of ω-Aminosubstituted-acetamidodiphenyl Ether Perivatives and Their Pharmacological Actions

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Abstract

Relationship between chemical structure and pharmacological activity was examined in ω-amino (substituted) acetamidodiphenyl derivatives. Samples were synthesized by the application of p-chloronitrobenzene or 1, 4-dichloro-2'-nitrobenzene to the potassium salt of the corresponding phenols to form 4 (or 2)-nitrodiphenyl ethers, which were reduced with stannous chloride and conc. hydrochloric acid, and the products acylated to ω-chloroacetamidodiphenyl ethers. The objective compounds (49 samples) were then obtained by the application of corresponding aliphatic secondary amines. Anti-acetylcholine and antihistamine activities of these samples were examined by the Magnus method, using excised intestine of a guinea pig. All the compounds were found to have a papaverine-like action, which was stronger when the ω-aminoacetamide group was in the position para to the oxygen bridge, and was also elevated when the substitutent in the benzene ring was in the ortho position rather than in the meta or para position. As for the ω-amino group, compounds possessing a substituent in the piperidine ring system had a stronger activity. Therefore, 4'-chloro-4-(piperidinoacetamido) diphenyl ether (52) was selected from such compounds and its specificity to smooth muscle organs was examined in detail. By the use of excised intestinal smooth muscle, suppressive effect of 52 against contraction by barium chloride and 5-HT was 3.8 and 4.9 times, respectively, of that of papaverine. With the excised tracheal smooth muscle, 52 suppressed the contraction by acetylcholine, histamine, and barium chloride only to 60% in a high concentration. Organ specificity of 52 was seen in smooth muscle of the digestive organ system (intestinal and Oddi sphincter muscle) rather than against tracheal smooth muscle.

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 98 (12), 1597-1606, 1978

    The Pharmaceutical Society of Japan

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