Figure 1: Photopharmacology of KATP channels: design, synthesis and characteristics of JB253.
From: Optical control of insulin release using a photoswitchable sulfonylurea
(a) The logic of a photoswitchable sulfonylurea: upon photoisomerization to the cis-state, JB253 becomes more active, closing the KATP channel. Thermal relaxation makes the compound less active or leads to dissociation, restoring the open form of the channel. Closure of KATP channels leads to depolarization, promoting calcium influx and ultimately insulin release. (b) Chemical structure of tolbutamide and glimepiride, which served as templates for JB253. (c) Synthesis, structure and switching characteristics of JB253. Sulfanilamide undergoes diazotization and is trapped with N,N-diethylaniline to yield an azobenzene-sulfonamide, which is converted to JB253 by cyclohexyl isocyanate. trans-JB253 can be reversibly switched to cis-JB253 with blue light and relaxes thermally. (d) ultraviolet/Vis spectra of JB253 in the dark (black) and during constant illumination with 460 nm (blue). (e) Crystal structure of trans-JB253 (CCDC: 1014606) and glimepiride (CSD: TOHBUN01) showing the structural similarity of both sulfonylureas.
