Medicinal Chemistry Research p. 1783 - 1795 (2019)
Update date:2022-08-04
Topics: Molecular docking Synthesis process Local anesthetic agents Fluoro-substituted Conclusion Molecular Docking Studies Future Directions References Introduction Synthesis of Fluoro-Substituted Lidocaine Analogues Sciatic Nerve Block Activity Evaluation Discussion
Li, Wen
Yan, Ying
Chang, Yingjie
Ding, Lina
Liu, Hongmin
You, Qidong
Thirty fluoro-substituted lidocaine analogs (10a–e, 11a–e, 14a–e, 15a–e, 18a–e and 19a–e) were synthesized, and their sciatic nerve block activity were evaluated as local anesthesia. Most of the compounds displayed significant potency, and compound 10a in particular was much more potent than the parent lidocaine. Fifteen analogs including 10a demonstrated pKa values of 7.5–7.8 suitable for local anesthesia. Compound 10a, 14e, and lidocaine were docked into three target receptors of local anesthetics by molecular docking studies to delineate structure-activity relationships and explain the differences in activities. Hydrophobic interactions and hydrogen bonds were identified key to molecular binding, suggesting that optimization of these interactions and/or trifluoro-substitution at the benzene ring of lidocaine could enhance the properties of lidocine analogs for local anesthesia.
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