Agnetta, Luca and Bermudez, Marcel and Riefolo, Fabio and Matera, Carlo and Claro, Enrique and Messerer, Regina and Littmann, Timo and Wolber, Gerhard and Holzgrabe, Ulrike and Decker, Michael (2019) Fluorination of Photoswitchable Muscarinic Agonists Tunes Receptor Pharmacology and Photochromic Properties. JOURNAL OF MEDICINAL CHEMISTRY, 62 (6). pp. 3009-3020. ISSN 0022-2623, 1520-4804
Full text not available from this repository. (Request a copy)Abstract
Red-shifted azobenzene scaffolds have emerged as useful molecular photoswitches to expand potential applications of photopharmacological tool compounds. As one of them, tetra-ortho-fluoro azobenzene is well compatible for the design of visible-light-responsive systems, providing stable and bidirectional photoconversions and tissue-compatible characteristics. Using the unsubstituted azobenzene core and its tetra-ortho-fluorinated analogue, we have developed a set of uni- and bivalent photoswitchable toolbox derivatives of the highly potent muscarinic acetylcholine receptor agonist iperoxo. We investigated the impact of the substitution pattern on receptor activity and evaluated the different binding modes. Compounds 9b and 15b show excellent photochemical properties and biological activity as fluorination of the azobenzene core alters not only the photochromic behavior but also the pharmacological profile at the muscarinic M-1 receptor. These findings demonstrate that incorporation of fluorinated azobenzenes not just may alter photophysical properties but can exhibit a considerably different biological profile that has to be carefully investigated.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-COUPLED RECEPTORS; IN-VIVO; BIVALENT LIGANDS; OPTICAL CONTROL; AZOBENZENE PHOTOSWITCHES; ACETYLCHOLINE-RECEPTORS; BINDING; DESIGN; FLUOROAZOBENZENES; MODULATORS; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Apr 2020 10:29 |
| Last Modified: | 15 Apr 2020 10:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27329 |
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