Synthesis, high-throughput screening and pharmacological characterization of β-lactam derivatives as TRPM8 antagonists.

ABSTRACT: The mammalian transient receptor potential melastatin channel 8 (TRPM8), highly expressed in trigeminal and dorsal root ganglia, mediates the cooling sensation and plays an important role in the cold hypersensitivity characteristic of some types of neuropathic pain, as well as in cancer. Consequently, the identification of selective and potent ligands for TRPM8 is of great interest. Here, a series of compounds, having a β-lactam central scaffold, were prepared to explore the pharmacophore requirements for TRPM8 modulation. Structure-activity studies indicate that the minimal requirements for potent β-lactam-based TRPM8 blockers are hydrophobic groups (benzyl preferentially or ^t Bu) on R¹, R², R³ and R⁵ and a short N-alkyl chain (≤3 car

SUBMITTER: de la Torre-Martinez R 

PROVIDER: S-EPMC5589751 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature