Synthesis and evaluation of carbaborane derivatives of indomethacin as cyclooxygenase inhibitors.

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Scholz M, Blobaum AL, Marnett LJ, Hey-Hawkins E

Synthesis and evaluation of carbaborane derivatives of indomethacin as cyclooxygenase inhibitors.

Bioorg Med Chem. 2011 May 15;19(10):3242-8. doi: 10.1016/j.bmc.2011.03.054. Epub 2011 Mar 27.

PubMed ID

21524587 [ View in PubMed

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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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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Indomethacin	Prostaglandin G/H synthase 2	IC 50 (nM)	750	N/A	N/A	Details