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Carborane‐Derived Local Anesthetics are Isomer Dependent
Author(s) -
Kracke George R.,
VanGordon Monika R.,
Sevryugina Yulia V.,
Kueffer Peter J.,
Kabytaev Kuanysh,
Jalisatgi Satish S.,
Hawthorne M. Frederick
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402369
Subject(s) - carborane , lidocaine , analgesic , chemistry , local anesthetic , pharmacology , stereochemistry , anesthetic , medicinal chemistry , anesthesia , medicine
Clinically there is a need for local anesthetics with a greater specificity of action on target cells and longer duration. We have synthesized a series of local anesthetic derivatives we call boronicaines in which the aromatic phenyl ring of lidocaine was replaced with ortho ‐, meta ‐, C,C’‐dimethyl meta ‐ and para ‐carborane clusters. The boronicaine derivatives were tested for their analgesic activity and compared with lidocaine using standard procedures in mice following a plantar injection. The compounds differed in their analgesic activity in the following order: ortho‐ carborane = C,C’‐dimethyl meta‐ carborane > para‐ carborane > lidocaine > meta‐ carborane derivative. Both ortho ‐boronicaine and C,C’‐dimethyl meta ‐boronicaine had longer durations of analgesia than lidocaine. Differences in analgesic efficacies are rationalized by variations in chemical structure and protein binding characteristics.