Photoswitchable Carbamazepine Analogs for Non‐Invasive Neuroinhibition In Vivo DOI Creative Commons
Luisa Camerin, Galyna Maleeva, Alexandre M. J. Gomila

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(38)

Published: June 18, 2024

Abstract A problem of systemic pharmacotherapy is off‐target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, are used against epilepsy and neuropathic pain but cause side There a need drugs that inhibit nerve signals locally on‐demand without affecting other regions the body. Photopharmacology aims to address this with light‐activated localized illumination in target organ. Here, we have developed photoswitchable derivatives widely prescribed drug carbamazepine. For purpose, expanded our method ortho azologization tricyclic meta / para N‐bridged diazocine. Our results validate concept cryptoazologs (uniquely exemplified by Carbazopine‐ 1 ) bring light Carbadiazocine ( 8 ), can be photoswitched between 400–590 nm (using violet LEDs halogen lamps) shows good drug‐likeness predicted safety. Both compounds display activity vitro translucent zebrafish larvae. also offers vivo analgesic efficacy (mechanical thermal stimuli) rat model simple compelling treatment demonstration non‐invasive illumination.

Language: Английский

Photoswitchable Carbamazepine Analogs for Non‐Invasive Neuroinhibition In Vivo DOI Creative Commons
Luisa Camerin, Galyna Maleeva, Alexandre M. J. Gomila

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(38)

Published: June 18, 2024

A problem of systemic pharmacotherapy is off-target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, are used against epilepsy and neuropathic pain but cause side There a need drugs that inhibit nerve signals locally on-demand without affecting other regions the body. Photopharmacology aims to address this with light-activated localized illumination in target organ. Here, we have developed photoswitchable derivatives widely prescribed drug carbamazepine. For purpose, expanded our method ortho azologization tricyclic meta/para N-bridged diazocine. Our results validate concept cryptoazologs (uniquely exemplified by Carbazopine-1) bring light Carbadiazocine (8), can be photoswitched between 400-590 nm (using violet LEDs halogen lamps) shows good drug-likeness predicted safety. Both compounds display activity vitro translucent zebrafish larvae. (8) also offers vivo analgesic efficacy (mechanical thermal stimuli) rat model simple compelling treatment demonstration non-invasive illumination.

Language: Английский

Citations

4
Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction DOI Creative Commons
T. Brandt,

Pascal Lentes,

Jeremy Rudtke

et al.

Beilstein Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 21, P. 490 - 499

Published: March 4, 2025

Diazocines are photoswitches derived from azobenzenes by bridging the two phenyl rings in ortho position with a CH2CH2 group forming an eight membered (diazocine) ring. Diazocine is superior to most almost all photophysical properties (switching efficiency, quantum yield, wavelengths etc.). The biggest advantage, especially photopharmacology and when used photoswitchable materials, inverted thermodynamic stability of switching states (isomers). Z isomer more stable than E form. However, one disadvantage that it shares frequently azobenzene efficiency decreases sharply increasing water content solvent. In recently published paper, we reported replacing CH2 bridge NCOCH3 not only confers intrinsic solubility, but also largely eliminates problem reduced aqueous solutions. order investigate chemistry this promising photoswitch unlock further applications, now strategies for synthesis derivatives, which based on cross-coupling reactions. Fourteen vinyl-, aryl-, cyano-, amino-substituted diazocines were prepared via Stille, Suzuki, Buchwald-Hartwig X-ray structures presented derivatives 1, 2 7.

Language: Английский

Citations

0
Photoswitchable Carbamazepine Analogs for Non‐Invasive Neuroinhibition In Vivo DOI Creative Commons
Luisa Camerin, Galyna Maleeva, Alexandre M. J. Gomila

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(38)

Published: June 18, 2024

Abstract A problem of systemic pharmacotherapy is off‐target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, are used against epilepsy and neuropathic pain but cause side There a need drugs that inhibit nerve signals locally on‐demand without affecting other regions the body. Photopharmacology aims to address this with light‐activated localized illumination in target organ. Here, we have developed photoswitchable derivatives widely prescribed drug carbamazepine. For purpose, expanded our method ortho azologization tricyclic meta / para N‐bridged diazocine. Our results validate concept cryptoazologs (uniquely exemplified by Carbazopine‐ 1 ) bring light Carbadiazocine ( 8 ), can be photoswitched between 400–590 nm (using violet LEDs halogen lamps) shows good drug‐likeness predicted safety. Both compounds display activity vitro translucent zebrafish larvae. also offers vivo analgesic efficacy (mechanical thermal stimuli) rat model simple compelling treatment demonstration non‐invasive illumination.

Language: Английский

Citations

0