roflumilast and Lung-Diseases

roflumilast has been researched along with Lung-Diseases* in 2 studies

Other Studies

2 other study(ies) available for roflumilast and Lung-Diseases

Article	Year
Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors. Bioorganic & medicinal chemistry letters, 2013, Jun-01, Volume: 23, Issue:11 2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50=150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50=25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50=7.5 nM) and TNF-α production in mouse splenocytes (IC50=9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50=18 mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex. Topics: Animals; Anti-Inflammatory Agents; Benzeneacetamides; Binding Sites; Catalytic Domain; Crystallography, X-Ray; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclic S-Oxides; Humans; Lipopolysaccharides; Lung Diseases; Mice; Phosphodiesterase 4 Inhibitors; Protein Binding; Pyrimidines; Spleen; Structure-Activity Relationship; Tumor Necrosis Factor-alpha	2013
Synthesis and biological evaluation of 5-carbamoyl-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors. Bioorganic & medicinal chemistry, 2013, Nov-15, Volume: 21, Issue:22 5-Carbamoyl-2-phenylpyrimidine derivative 2 has been identified as a phosphodiesterase 4 (PDE4) inhibitor with moderate PDE4B inhibitory activity (IC50=200 nM). Modification of the carboxylic acid moiety of 2 gave N-neopentylacetamide derivative 10f, which had high in vitro PDE4B inhibitory activity (IC50=8.3 nM) and in vivo efficacy against lipopolysaccharide (LPS)-induced pulmonary neutrophilia in mice (ID50=16 mg/kg, ip). Furthermore, based on the X-ray crystallography of 10f bound to the human PDE4B catalytic domain, we designed 7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one derivative 39 which has a fused bicyclic lactam scaffold. Compound 39 exhibited excellent inhibitory activity against LPS-induced tumor necrosis factor alpha (TNF-α) production in mouse splenocytes (IC50=0.21 nM) and in vivo anti-inflammatory activity against LPS-induced pulmonary neutrophilia in mice (41% inhibition at a dose of 1.0 mg/kg, i.t.). Topics: Animals; Anti-Inflammatory Agents; Binding Sites; Catalytic Domain; Cells, Cultured; Crystallography, X-Ray; Cyclic Nucleotide Phosphodiesterases, Type 4; Enzyme Activation; Humans; Lipopolysaccharides; Lung Diseases; Mice; Phosphodiesterase 4 Inhibitors; Pyridones; Pyrimidines; Spleen; Tumor Necrosis Factor-alpha	2013

Article

Year

Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.

Bioorganic & medicinal chemistry letters, 2013, Jun-01, Volume: 23, Issue:11

2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50=150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50=25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50=7.5 nM) and TNF-α production in mouse splenocytes (IC50=9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50=18 mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex.

Topics: Animals; Anti-Inflammatory Agents; Benzeneacetamides; Binding Sites; Catalytic Domain; Crystallography, X-Ray; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclic S-Oxides; Humans; Lipopolysaccharides; Lung Diseases; Mice; Phosphodiesterase 4 Inhibitors; Protein Binding; Pyrimidines; Spleen; Structure-Activity Relationship; Tumor Necrosis Factor-alpha

2013

Synthesis and biological evaluation of 5-carbamoyl-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.

Bioorganic & medicinal chemistry, 2013, Nov-15, Volume: 21, Issue:22

5-Carbamoyl-2-phenylpyrimidine derivative 2 has been identified as a phosphodiesterase 4 (PDE4) inhibitor with moderate PDE4B inhibitory activity (IC50=200 nM). Modification of the carboxylic acid moiety of 2 gave N-neopentylacetamide derivative 10f, which had high in vitro PDE4B inhibitory activity (IC50=8.3 nM) and in vivo efficacy against lipopolysaccharide (LPS)-induced pulmonary neutrophilia in mice (ID50=16 mg/kg, ip). Furthermore, based on the X-ray crystallography of 10f bound to the human PDE4B catalytic domain, we designed 7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one derivative 39 which has a fused bicyclic lactam scaffold. Compound 39 exhibited excellent inhibitory activity against LPS-induced tumor necrosis factor alpha (TNF-α) production in mouse splenocytes (IC50=0.21 nM) and in vivo anti-inflammatory activity against LPS-induced pulmonary neutrophilia in mice (41% inhibition at a dose of 1.0 mg/kg, i.t.).

Topics: Animals; Anti-Inflammatory Agents; Binding Sites; Catalytic Domain; Cells, Cultured; Crystallography, X-Ray; Cyclic Nucleotide Phosphodiesterases, Type 4; Enzyme Activation; Humans; Lipopolysaccharides; Lung Diseases; Mice; Phosphodiesterase 4 Inhibitors; Pyridones; Pyrimidines; Spleen; Tumor Necrosis Factor-alpha

2013