Synthesis and Evaluation of Carbaborane Derivatives of Indomethacin As Cyclooxygenase Inhibitors

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2011 Apr 29

PMID 21524587

Citations 12

Authors

Matthias Scholz

Anna L Blobaum

Lawrence J Marnett

Evamarie Hey-Hawkins

Affiliations

Soon will be listed here.

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological activities by inhibiting cyclooxygenase (COX)-1 and COX-2. Previous studies have shown that esters and amides of non-selective inhibitors such as indomethacin are selective against COX-2, which is the therapeutically relevant isoform. Structure-activity analysis indicates that substituted phenyl rings are tolerated as ester components. In the present study, the introduction of inorganic ortho- and meta-carbaborane moieties was explored with the aim to create COX-2 inhibitors and more importantly to investigate the validity of using these boron clusters as drug entities. Interestingly, only the ortho-carbaborane ester was active whereas the meta isomer was not. A similar lack of inhibitory potency was observed when an adamantyl substituent or alkylene spacers at the carbaborane were introduced in the ester functionality.

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