沿岸海洋景観のGISデータベースの構築

<p>Superimposition of the top poses of LASSBio-448 obtained by docking with PDE4A and PDE4C (light purple surface, PDE4A) (A), PDE4B and PDE4D (gold surface, PDE4D) (B). Hydrogen atoms have been omitted for clarity.</p

Effect of LASSBio-448 and cilomilast on lung pathological changes caused by LPS in mice.

<p>LASSBio-448 (2.5 and 10 mg/kg, oral) or cilomilast (1 mg/kg, oral) were given 1 h before challenge (LPS, 25 μg/25 μL), and analyses on airway hyper-reactivity (A) and neutrophil infiltration, attested by MPO activity of lung tissue samples (B), were carried out 24 h post challenge. Values represent mean ± SEM from at least 7 animals. + <i>P</i><0.05 as compared to vehicle-stimulated group; *<i>P</i><0.05 as compared to LPS-stimulated mice.</p

Genesis concept of sulfonamides (5 and 6a-k) designed as PDE4 inhibitors.

<p>Genesis concept of sulfonamides (5 and 6a-k) designed as PDE4 inhibitors.</p

PDE4 Inhibition of rolipram and sulfonamides 5 and 6a-k.

<p>PDE4 Inhibition of rolipram and sulfonamides 5 and 6a-k.</p

Effect of rolipram and LASSBio-448 on ovalbumin (OVA)-induced changes in lungs from A/J mice.

<p>Airway responsiveness was measured by changes in airway resistance (A) and elastance (B) induced by increasing concentrations of methacholine, 24 h after the last ovalbumin or saline challenge. Animals were sensitized on days 0 and 7 and then challenged with OVA (25 μg/mouse) or saline on days 14, 21, 28 and 35. Animals were treated with rolipram (10 mg/Kg, oral) or LASSBio-448 (100 mg/Kg, oral) on days 26 and 22, 1 h before OVA challenge, and analyses performed 24 h after the last challenge. Values represent mean ± SEM from at least 7 animals. + <i>P</i><0.05 as compared to saline-challenged group; *<i>P</i><0.05 as compared to OVA-challenged group.</p

Synthesis sulfonamide derivatives.

<p>Reagents and conditions: a) 1) H₂SO₄ /Ac₂O /AcOEt, 0°C, 2 h; 2) AcOK / EtOH, 25°C, 30 min, 93%. b) SOCl₂, DMF, 75°C, 4 h, 92%. c) CH₂Cl₂, Et₃N, 2-(3,4-dimethoxyphenyl)ethanamine (<b>6a</b>) or 2-phenylethanamine (5), 25°C, 2–2.5 h, 70%-81% respectively. d) K₂CO₃, acetone, RX (X = I, Br), (<b>6b-6e, 6g-6i</b> and <b>6k</b>), 40°C, 1.5 h, 34–96%. e) CH₂Cl₂, Et₃N, 2-(3,4-dimethoxyphenyl)ethanamine (<b>6f, 6j</b>) 25°C, 2–2.5 h, 53%-83% respectively.</p

Reduction by LASSBio-448, rolipram or cilomilast in duration of the ketamine/xylazine anesthesia (%).

<p>Mice of the strain A/J were injected with ketamine/ xylazine solution and then treated orally with LASSBio-448 (3, 10 and 30 mg/kg), rolipram (1, 3 and 10 mg/kg) or cilomilast (1 mg/kg). Values represent mean ± SEM from at least 7 animals. Figures in brackets shown in the top of each column are correspondent doses expressed in μmol/kg. *<i>P</i><0.05 as compared to vehicle-treated group.</p

PDE4 recombinant isoform inhibition (IC₅₀, μM) for sulfonamide 6a (LASSBio-448) and rolipram.

<p>PDE4 recombinant isoform inhibition (IC₅₀, μM) for sulfonamide 6a (LASSBio-448) and rolipram.</p

Examples of PDE4 inhibitors of first and second generations.

<p>Examples of PDE4 inhibitors of first and second generations.</p

Effect of rolipram and LASSBio-448 on ovalbumin (OVA)-induced infiltration of eosinophils in the lung tissue from A/J mice.

<p>Animals were sensitized on days 0 and 7 and then challenged with OVA (25 μg/mouse) or saline on days 14, 21, 28 and 35. Animals were treated with rolipram (10 mg/Kg, oral) or LASSBio-448 (100 mg/Kg, oral) on days 26 and 22, 1 h before OVA challenge, and analyses performed 24 h after the last challenge. Values represent mean ± SEM from at least 7 animals. + P<0.05 as compared to saline-challenged group; *<i>P</i><0.05 as compared to OVA-challenged group.</p