PDE4 inhibitor 16   

GtoPdb Ligand ID: 10400

Compound class: Synthetic organic
Comment: This compound has been reported as a selective inhibitor of phosphodiesterase 4 (PDE4) [1]. Chemically this compound is a synthetic tetrahydro-isoquinoline analogue of the naturally occurring plant alkaloid berberine (PubChem CID 2353).
2D Structure
Click here for structure editor
Physico-chemical Properties
Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 54.56
Molecular weight 378.19
XLogP 3.61
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES O=CN1CCc2c(C1CCc1c[nH]c3c1ccc(c3)C)cc(c(c2)OC)OC
Isomeric SMILES O=CN1CCc2c([C@@H]1CCc1c[nH]c3c1ccc(c3)C)cc(c(c2)OC)OC
InChI InChI=1S/C23H26N2O3/c1-15-4-6-18-17(13-24-20(18)10-15)5-7-21-19-12-23(28-3)22(27-2)11-16(19)8-9-25(21)14-26/h4,6,10-14,21,24H,5,7-9H2,1-3H3/t21-/m0/s1
InChI Key OIDQRHGTWLIKKZ-NRFANRHFSA-N
Bioactivity Comments
Although compound 16 is reported to exhibit selectivity for PDE4, data in the table below shows that its in vitro selectivity over PDE10 is only ~4 fold. Compound 16 inhibits lipopolysaccharide (LPS)-stimulated TNFα production by human peripheral blood mononuclear cells with an IC50 of 650 nM [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
phosphodiesterase 4D Hs Inhibitor Inhibition 6.6 pIC50 - 1
pIC50 6.6 (IC50 2.4x10-7 M) [1]
Description: Inhibition of enzymatic activity of the recombinant human PDE4D catalytic domain in vitro.
phosphodiesterase 10A Hs Inhibitor Inhibition 6.0 pIC50 - 1
pIC50 6.0 (IC50 9.2x10-7 M) [1]
Description: Inhibition of enzymatic activity of the recombinant human PDE10A catalytic domain in vitro.
phosphodiesterase 6C Hs Inhibitor Inhibition 5.5 pIC50 - 1
pIC50 5.5 (IC50 3.3x10-6 M) [1]
Description: Inhibition of enzymatic activity of the recombinant human PDE6C catalytic domain in vitro.