Small Molecule CNS compounds for neuropathic pain

“In general, neuropathic pain conditions are under-recognized, underdiagnosed, and undertreated.” The challenge to treating this disease is finding a safe, brain penetrating small molecule that effects the root cause. AAK1 show promise as a target, and this paper show the progress of a series of bi-aryl compounds. CNS penetration, kinase selectivity and safety (CYP3A4 inhibition) were the key areas to optimise, and in-vivo activity was achieved. [Currently this paper is open to download without subscription]

AAK1 CNS cmpds

Discovery and Optimization of Biaryl Alkyl Ethers as a Novel Class of Highly Selective, CNS-Penetrable, and Orally Active Adaptor Protein-2-Associated Kinase 1 (AAK1) Inhibitors for the Potential Treatment of Neuropathic Pain

Luo, G. et al

J. Med. Chem. 2022, 65, 6, 4534–4564