β-Lactam TRPM8 Antagonists Derived from Phe-Phenylalaninol Conjugates: Structure-Activity Relationships and Antiallodynic Activity.

ABSTRACT: The protein transient receptor potential melastatin type 8 (TRPM8), a non-selective, calcium (Ca²⁺)-permeable ion channel is implicated in several pathological conditions, including neuropathic pain states. In our previous research endeavors, we have identified β-lactam derivatives with high hydrophobic character that exhibit potent and selective TRPM8 antagonist activity. This work describes the synthesis of novel derivatives featuring C-terminal amides and diversely substituted N'-terminal monobenzyl groups in an attempt to increase the total polar surface area (TPSA) in this family of compounds. The primary goal was to assess the influence of these substituents on the inhibition of menthol-induced cellular Ca²⁺ entry, thereby establishing critical str

SUBMITTER: Martin-Escura C 

PROVIDER: S-EPMC10573892 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature