Trisubstituted Sulfonamides: A New Chemotype for Development
of Potent and Selective CB<sub>2</sub> Receptor Inverse Agonists
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Abstract
An
extensive exploration of the structure–activity relationship
of a trisubstituted sulfonamide series led to the identification of <b>39</b>, which is a potent and selective CB<sub>2</sub> receptor
inverse agonist [<i>K</i><sub>i</sub>(CB<sub>2</sub>) =
5.4 nM, and <i>K</i><sub>i</sub>(CB<sub>1</sub>) = 500 nM].
The functional properties measured by cAMP assays indicated that the
selected compounds were CB<sub>2</sub> inverse agonists with high
potency values (for <b>34</b>, EC<sub>50</sub> = 8.2 nM, and
for <b>39</b>, EC<sub>50</sub> = 2.5 nM). Furthermore, an osteoclastogenesis
bioassay indicated that trisubstituted sulfonamide compounds showed
great inhibition of osteoclast formation
