Synthesis and potassium channel opening activity of substituted 10H-benzo[4,5]furo[3,2-b]indole-and 5,10-dihydro-indeno[1,2-b]indole-1-carboxylic acids.

Abstract

Compounds in a structurally novel series of substituted 10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acids and related 5,10-dihydro-indeno[1,2-b]indole-1-carboxylic acids were prepared and shown to possess potent, bladder-selective smooth muscle relaxant properties and thus are potentially useful for the treatment of urge urinary incontinence. Electrophysiological studies using rat detrusor myocytes have demonstrated that prototype compound 7 produces a significant increase in hyperpolarizing current, which is iberiotoxin (IbTx)-reversed, thus consistent with activation of the large-conductance Ca(2+)-activated potassium channel (BK(Ca)).

• Authors: J A Butera, S A Antane, B Hirth, J R Lennox, J H Sheldon, N W Norton, D Warga, T M Argentieri
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 11 Issue 16 Pg. 2093-7 (Aug 20 2001) ISSN: 0960-894X [Print] England
• PMID: 11514146 (Publication Type: Journal Article)

Chemical References

• 10H-benzo(4,5)furo(3,2-b)indole-1-carboxylic acid
• 5,10-dihydro-indeno(1,2-b)indole-1-carboxylic acid
• Carboxylic Acids
• Indoles
• Parasympatholytics
• Potassium Channels

Topics

• Animals
• Carboxylic Acids (chemical synthesis, chemistry, pharmacology)
• Indoles (chemical synthesis, chemistry, pharmacology)
• Muscles (cytology, drug effects)
• Parasympatholytics (chemical synthesis, chemistry, pharmacology)
• Potassium Channels (agonists, metabolism)
• Rats