Structure-activity relationship studies of four novel 4-aminopyridine K⁺ channel blockers.

ABSTRACT: 4-Aminopyridine (4AP) is a specific blocker of voltage-gated potassium channels (K_V1 family) clinically approved for the symptomatic treatment of patients with multiple sclerosis (MS). It has recently been shown that [¹⁸F]3F4AP, a radiofluorinated analog of 4AP, also binds to K_V1 channels and can be used as a PET tracer for the detection of demyelinated lesions in rodent models of MS. Here, we investigate four novel 4AP derivatives containing methyl (-CH₃), methoxy (-OCH₃) as well as trifluoromethyl (-CF₃) in the 2 and 3 position as potential candidates for PET imaging and/or therapy. We characterized the physicochemical properties of these compounds (basicity and lipophilicity) and analyzed their ability to block Shaker K

SUBMITTER: Rodriguez-Rangel S 

PROVIDER: S-EPMC6952366 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature