sew2871 and Cardiovascular-Diseases

sew2871 has been researched along with Cardiovascular-Diseases* in 1 studies

Other Studies

1 other study(ies) available for sew2871 and Cardiovascular-Diseases

Article	Year
Quinolinone-based agonists of S1P₁: use of a N-scan SAR strategy to optimize in vitro and in vivo activity. Bioorganic & medicinal chemistry letters, 2012, Jan-01, Volume: 22, Issue:1 We reveal how a N-scan SAR strategy (systematic substitution of each CH group with a N atom) was employed for quinolinone-based S1P(1) agonist 5 to modulate physicochemical properties and optimize in vitro and in vivo activity. The diaza-analog 17 displays improved potency (hS1P(1) RI; 17: EC(50)=0.020 μM, 120% efficacy; 5: EC(50)=0.070 μM, 110% efficacy) and selectivity (hS1P(3) Ca(2+) flux; 17: EC(50) >25 μM; 5: EC(50)=1.5 μM, 92% efficacy), as well as enhanced pharmacokinetics (17: CL=0.15 L/h/kg, V(dss)=5.1L/kg, T(1/2)=24h, %F=110; 5: CL=0.93L/h/kg, V(dss)=11L/kg, T(1/2)=15 h, %F=60) and pharmacodynamics (17: 1.0mg/kg po, 24h PLC POC=-67%; 5: 3mg/kg po, 24h PLC POC=-51%) in rat. Topics: Animals; Area Under Curve; Cardiovascular Diseases; Chemistry, Physical; Drug Design; Female; Humans; Immunosuppressive Agents; In Vitro Techniques; Kinetics; Lymphocytes; Models, Chemical; Multiple Sclerosis; Quinolones; Rats; Rats, Inbred Lew; Receptors, Lysosphingolipid; Structure-Activity Relationship	2012

Article

Year

Quinolinone-based agonists of S1P₁: use of a N-scan SAR strategy to optimize in vitro and in vivo activity.

Bioorganic & medicinal chemistry letters, 2012, Jan-01, Volume: 22, Issue:1

We reveal how a N-scan SAR strategy (systematic substitution of each CH group with a N atom) was employed for quinolinone-based S1P(1) agonist 5 to modulate physicochemical properties and optimize in vitro and in vivo activity. The diaza-analog 17 displays improved potency (hS1P(1) RI; 17: EC(50)=0.020 μM, 120% efficacy; 5: EC(50)=0.070 μM, 110% efficacy) and selectivity (hS1P(3) Ca(2+) flux; 17: EC(50) >25 μM; 5: EC(50)=1.5 μM, 92% efficacy), as well as enhanced pharmacokinetics (17: CL=0.15 L/h/kg, V(dss)=5.1L/kg, T(1/2)=24h, %F=110; 5: CL=0.93L/h/kg, V(dss)=11L/kg, T(1/2)=15 h, %F=60) and pharmacodynamics (17: 1.0mg/kg po, 24h PLC POC=-67%; 5: 3mg/kg po, 24h PLC POC=-51%) in rat.

Topics: Animals; Area Under Curve; Cardiovascular Diseases; Chemistry, Physical; Drug Design; Female; Humans; Immunosuppressive Agents; In Vitro Techniques; Kinetics; Lymphocytes; Models, Chemical; Multiple Sclerosis; Quinolones; Rats; Rats, Inbred Lew; Receptors, Lysosphingolipid; Structure-Activity Relationship

2012