Cyclic nucleotide-gated (CNG) ion channels are important in the light transduction process of eyesight. A specific form of retinitis pigmentosa causes CNG channels to remain open, leading to a buildup of calcium in the cell that results in blindness. Potential treatments include ion channel blockers that bind inside open channels to regulate the influx of cations. Tetracaine has been shown to block CNG channels with moderate affinity and specificity. This research focuses on the design and synthesis of novel derivatives of tetracaine, in order to develop potent blockers of CNG channels, and to better understand the functional architecture of the pore.  We will present results that include a series of molecules with electron-withdrawing groups incorporated on the central aromatic ring, as well as derivatives that vary the connectivity of the tail to the ring.  Early results indicate that the acidity of the aniline amine is essential for blocking.

Design and synthesis of tetratcaine deriviatives as CNG channel blockers

245th National Meeting (2013)

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