T-type calcium channels inhibitors: a patent review.

IMPORTANCE OF THE FIELD: T-type calcium channels are transmembrane proteins that regulate calcium entry in the cell in a voltage-dependent manner. Intracellular calcium levels are the key to many physiological processes, ranging from neuron firing to cardiac pacemaking. Inhibition of T-type calcium channels is heralded as a potential treatment to peripheral and CNS disorders, including hypertension, heart failure, sleep, epilepsy, drug addiction and neuropathic pain. AREAS COVERED IN THIS REVIEW: A comprehensive summary of patent literature disclosing T-type calcium channels inhibitors is provided. WHAT THE READER WILL GAIN: In all, 46 patent applications including 15 chemical structure classes are reviewed. Available in vitro, in vivo and clinical results are also discussed. TAKE HOME MESSAGE: Several selective T-type calcium channels inhibitors with demonstrated in vitro and in vivo effects, including one Phase I clinical candidate, are now available. While future clinical results will be paramount to assess target validity in patients, these novel inhibitors represent excellent tools to further investigate the role of T-type channels in pathophysiological conditions.