Carborane‐Derived Local Anesthetics are Isomer Dependent. Issue 1 (24th November 2014)

• Record Type: Journal Article
• Authors: Kracke, George R.; VanGordon, Monika R.; Sevryugina, Yulia V.; Kueffer, Peter J.; Kabytaev, Kuanysh; Jalisatgi, Satish S.; Hawthorne, M. Frederick
• Is Part Of: ChemMedChem. Volume 10:Issue 1(2015:Jan.)
• Page Start: 62
• Page End: 67
• Publication Date: 2014-11-24
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201402369
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <italic>ortho</italic>‐, <italic>meta</italic>‐, C, C'‐dimethyl <italic>meta</italic>‐ and <italic>para</italic>‐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: <italic>ortho‐</italic>carborane = C, C'‐dimethyl <italic>meta‐</italic>carborane &gt; <italic>para‐</italic>carborane &gt; lidocaine &gt; <italic>meta‐</italic>carborane derivative. Both <italic>ortho</italic>‐boronicaine and C, C'‐dimethyl <italic>meta</italic>‐boronicaine had longer durations of analgesia than lidocaine. Differences in analgesic efficacies are rationalized by variations in chemical structure and protein binding characteristics.</p> </abstract>