Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors†,10.1039/C3OB27424A

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Lactoyl-CoA 全氟丁基戊烷白叶藤碱全氟己基辛烷新白叶藤碱壳寡糖特色专题-生物多肽

Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors†

Soumita Mukherjee,Chandana Lakshmi T. Meda,Girdhar Singh Deora,K. Lalith Kumar,Kishore V. L. Parsa,K. Mukkanti,Manojit Pal

Organic & Biomolecular Chemistry Pub Date : 02/11/2013 00:00:00 , DOI:10.1039/C3OB27424A

Abstract

A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC₅₀ 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.