Imatinib is the first protein kinase inhibitor approved for clinical use and is a seminal drug for the concept of targeted therapy. Herein we report on the design, synthesis, photokinetic properties, and in vitro enzymatic evaluation of a photoactivatable caged prodrug of imatinib. This approach allows spatial and temporal control over the activation of imatinib triggered by ultraviolet light. The successful application of the photoactivation concept to this significant kinase inhibitor provides further evidence for the caging technique as a feasible approach in the kinase field. The presented photoactivatable imatinib prodrug will be highly useful as a pharmacological tool to study the impact of imatinib toward biological systems in greater detail.
A [2]rotaxane shuttle for (light‐driven) proton transport has been designed and synthesized. The rotaxane contains a macrocyclic ring that carries a pyridine nitrogen atom as a basic center to bind and to transport a proton. The axis includes an amide binding site for the macrocycle and a positive charge in close vicinity. Upon protonation of the pyridine nitrogen atom, the hydrogen bond is broken and Coulomb repulsion between the protonated pyridine and the permanent positive charge in the axis pushes the protonated macrocycle to the other end of the axis. By variation of the pH the ring can shuttle to and fro. Its locations on the axis were determined by NMR spectroscopy.
A set of 27‐ to 39‐membered pyridine macrocycles 2 and 3 has been synthesized by Williamson ether synthesis or ring‐closing metathesis. The pyridines are 2,6‐disubstituted to allow endo interactions. In addition to the length, also thenature of the aliphatic chain was varied: saturated (2) and unsaturated (3).
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