Potent nor-triterpenoid blockers of the voltage-gated potassium channel Kv1.3 from Spachea correae

K+ Channel Modulators for the Treatment of Neurological Disorders and Autoimmune Diseases

“…334 Correolide blocks K V 1.3 with an IC 50 of 90 nM 264,335 and two correolide derivatives, which cause less hyperactivity than correolide in vivo, have been shown to suppress delayed type hypersensitivity in minipigs. 336 However, because of their lack of selectivity over K V 1.2, K V 1.5, K V 1.6, and especially K V 1.1, 337 correolide (37) and its derivatives increase the peristaltic activity of the gastrointestinal tract by increasing acetylcholine and tachykinin release.…”

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“…The semirigid molecule of correolide seen in the X-ray structure [27] has the shape of a flattened ellipsoid with epoxide oxygen at one pole and carbonyl oxygen in the seven-membered ring at another. Let us define the long axis of correolide as a line drawn between the poles, which are ~12 Å apart.…”

Importance of biodiversity to the modern pharmaceutical industry

“…[4] Plant samples have also derived interesting structures which have been used as leads for Merck research. One example is correolide (3), a triterpene derived from Spachea correae collected in Costa Rica and shown to be a potent reversible blocker of a potassium channel important in T-cell receptor activation [5]. Due to the complexity of the structure and its less than optimal pharmaceutical properties, it could not be used as such.…”