1. Academic Validation
  2. Synthesis and biological evaluation of desmethylveramiline, a micromolar Hedgehog inhibitor

Synthesis and biological evaluation of desmethylveramiline, a micromolar Hedgehog inhibitor

  • Bioorg Med Chem Lett. 2011 Jun 15;21(12):3608-12. doi: 10.1016/j.bmcl.2011.04.103.
Guillaume Guerlet 1 Thomas Spangenberg André Mann Hélène Faure Martial Ruat
Affiliations

Affiliation

  • 1 Laboratoire d'Innovation Thérapeutique, UMR 7200 CNRS-Université de Strasbourg Faculté de Pharmacie, Illkirch, France.
Abstract

Desmethylveramiline (1), an aza steroid analogue of veramiline was designed as a surrogate for cyclopamine, a reference antagonist of the Sonic Hedgehog (Shh) pathway. Desmethyveramiline (1) was prepared in seven steps from commercially available Fernholtz acid using the hydroformylation of a terminal olefine as the key step for the construction of the piperidine appendage. In two assays (i) the inhibition of the Shh-induced Gli-dependent luciferase activity in Shh-light2 cells, (ii) the inhibition of the SAG-induced differentiation of the mesenchymal C3H10T1/2 cells, desmethylveramiline (1) is an inhibitor in the μM range comparable to cyclopamine.

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