Thalidomide analogs and PDE4 inhibition
N-Phthaloyl 3-amino-3-arylpropionic acid analogs of thalidomide that are potent inhibitors of tumor necrosis factor-α are reported. These compounds were found to be potent inhibitors of phosphodiesterase 4.
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Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions
2022, Current Research in Pharmacology and Drug DiscoveryCitation Excerpt :Similarly, thalidomide 100 μM has been reported to inhibit contractions of prostate smooth muscle (Tamalunas et al., 2020). For each study, the mechanism of the inhibitory activity was not explored, but muscle relaxation by PDE4 inhibition seems unlikely as, the IC50 for thalidomide against PDE4 was >500 μM (Muller et al., 1998). This conclusion is further supported by the demonstration that THD (100 μM) did not elevate cAMP in human peripheral blood mononuclear cells in contrast to apremilast which showed binding to PDE4 whereas THD did not (Schafer et al., 2014).
Thalidomide and analogues
2019, Imides: Medicinal, Agricultural, Synthetic Applications and Natural Products ChemistryThalidomide analogues: Tumor necrosis factor-alpha inhibitors and their evaluation as anti-inflammatory agents
2016, European Journal of Pharmaceutical SciencesCitation Excerpt :This cytokine plays a critical role in several physiological immunological processes, causing severe damage when produced in excess. A number of phthalimide derivatives have been previously synthesized employing different strategies in order to obtain molecules that can act as modulators of the over production of TNF-α (Niwayama et al., 1998; Muller et al., 1998; Lima et al., 2002; Cupertino Da Silva et al., 2010; Stewart et al., 2007; Zhu et al., 2003; Machado et al., 2005; Chaulet et al., 2011; Tweedie et al., 2011). In an attempt to maintain the beneficial properties while avoiding its side effects, new achiral synthetic thalidomide analogues have been designed.
Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity
2014, Cellular SignallingCrystal structure of an apremilast ethanol hemisolvate hemihydrate solvatomorph
2017, Acta Crystallographica Section E: Crystallographic Communications