Query String: ROFLUMILAST
DAXAS ROF 3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide BDBM14774 CHEMBL193240 Roflumilast
- Boland, S; Alen, J; Bourin, A; Castermans, K; Boumans, N; Panitti, L; Vanormelingen, J; Leysen, D; Defert, O Novel Roflumilast analogs as soft PDE4 inhibitors. Bioorg Med Chem Lett 24: 4594-7 (2014)
- Hu, J; Pan, T; An, B; Li, Z; Li, X; Huang, L Synthesis and evaluation of clioquinol-rolipram/roflumilast hybrids as multitarget-directed ligands for the treatment of Alzheimer's disease. Eur J Med Chem 163: 512-526 (2019)
- Liu, A; Huang, L; Wang, Z; Luo, Z; Mao, F; Shan, W; Xie, J; Lai, K; Li, X Hybrids consisting of the pharmacophores of salmeterol and roflumilast or phthalazinone: dualß2-adrenoceptor agonists-PDE4 inhibitors for the treatment of COPD. Bioorg Med Chem Lett 23: 1548-52 (2013)
- Moussa, BA; El-Zaher, AA; El-Ashrey, MK; Fouad, MA Synthesis and molecular docking of new roflumilast analogues as preferential-selective potent PDE-4B inhibitors with improved pharmacokinetic profile. Eur J Med Chem 148: 477-486 (2018)
- Inhibition Assay A TR-FRET-based phosphodiesterase assay kit from Molecular Devices was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an IMAP binding reagent, which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.
- TR-FRET-Based Phosphodiesterase Assay A TR-FRET-based phosphodiesterase assay kit from "Molecular Devices" was used to test whether these compounds were indeed direct inhibitors of the PDE4 enzyme. Using Roflumilast as a positive control, compounds of the present invention were tested against fluorescein-labeled cAMP substrate. The principle of the assay is based on the binding of a nucleotide monophosphate generated upon cAMP conversion to 5′ AMP by PDE to an "IMAP binding reagent", which in turn is also ligated to a separate complex carrying terbium (Tb)-donor molecule. Proximity of the fluoreceinated 5′AMP to the Tb donor generates Fluorescence Resonance Energy Transfer. A PDE inhibitor will reduce the conversion of cAMP to 5′AMP, thus reducing monophosphate that can bind to the IMAP binding reagent and reduce the resulting FRET signal.