Difamilast

Difamilast is an inhibitor of phosphodiesterase 4 (PDE4). It is selective for the PDE4 isoforms PDE4A, PDE4B, PDE4C, and PDE4D (IC50s = 0.0832, 0.0112, 0.2493 and 0.0738 µM, respectively) over PDE5A and PDE10A (IC50s = 4.793 and 1.4346 µM, respectively) and eight other PDEs (IC50s = >10 µM for all). Difamilast (0.01-10 µM) increases intracellular cAMP levels in U937 cells. It inhibits LPS-induced increases in TNF-alpha secretion from isolated human and mouse peripheral blood mononuclear cells (PBMCs, IC50s = 19 and 3.5 nM, respectively). Topical application of difamilast (3% w/v) decreases ear thickness and CD3+ T cell, eosinophil, and neutrophil lesion infiltrates in a mouse model of 2,4,6-trinitrochlorobenzene-induced chronic allergic contact dermatitis. Formulations containing difamilast have been used in the treatment of atopic dermatitis.Formal Name: N-[[2-[4-(difluoromethoxy)-3-(1-methylethoxy)phenyl]-4-oxazolyl]methyl]-2-ethoxy-benzamide. CAS Number: 937782-05-3. Synonyms: OPA 15406. Molecular Formula: C23H24F2N2O5. Formula Weight: 446.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Soluble, DMSO: Soluble. SMILES: O=C(C1=CC=CC=C1OCC)NCC2=COC(C3=CC(OC(C)C)=C(OC(F)F)C=C3)=N2. InChi Code: InChI=1S/C23H24F2N2O5/c1-4-29-18-8-6-5-7-17(18)21(28)26-12-16-13-30-22(27-16)15-9-10-19(32-23(24)25)20(11-15)31-14(2)3/h5-11,13-14,23H,4,12H2,1-3H3,(H,26,28). InChi Key: VFBILHPIHUPBPZ-UHFFFAOYSA-N.