New bronchodilators. II. 3H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel 3-substituted imidazo[4,5-c]quinolin-4(5H)-ones (2a-w) was prepared by the reaction of imidazo[4,5-c]quinolin-4(5H)-ones (6) with several electrophiles under basic conditions. The bronchodilatory activity of these compounds was evaluated on the basis of their protective effects against antigen-induced contraction (the Schultz-Dale reaction) of guinea-pig trachea (in vitro) and antigen inhalation-induced bronchospasm in passively sensitized guinea-pigs (in vivo). Although correlations between in vitro and in vivo activities were not clear, short alkyl chains such as the methyl and ethyl groups at the 3-position were important for potent activity, especially in vivo. Substituents at the 5-position were more tolerant of the activity than those at the 3-position. 5-Ethyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one (21) exhibits the most potent bronchodilatory activity among our tested compounds and is at least 5-fold more active than theophylline in vivo.
AuthorsF Suzuki, T Kuroda, H Hayashi, Y Nakasato, H Manabe, K Ohmori, S Kitamura
JournalChemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 40 Issue 12 Pg. 3245-52 (Dec 1992) ISSN: 0009-2363 [Print] JAPAN
PMID1294327 (Publication Type: Journal Article)
Chemical References
  • Bronchodilator Agents
  • Imidazoles
  • Quinolines
  • Theophylline
  • Animals
  • Bronchial Spasm (prevention & control)
  • Bronchodilator Agents (administration & dosage, chemical synthesis, pharmacology)
  • Guinea Pigs
  • Imidazoles (administration & dosage, chemical synthesis, pharmacology)
  • In Vitro Techniques
  • Male
  • Quinolines (administration & dosage, chemical synthesis, pharmacology)
  • Structure-Activity Relationship
  • Theophylline (administration & dosage, pharmacology)
  • Trachea (drug effects)

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