pyrrophenone and Edema

pyrrophenone has been researched along with Edema* in 2 studies

Other Studies

2 other study(ies) available for pyrrophenone and Edema

Article	Year
Design, synthesis, and biological evaluation of 3-(1-Aryl-1H-indol-5-yl)propanoic acids as new indole-based cytosolic phospholipase A2α inhibitors. Journal of medicinal chemistry, 2014, Sep-11, Volume: 57, Issue:17 This article describes the design, synthesis, and biological evaluation of new indole-based cytosolic phospholipase A2α (cPLA2α, a group IVA phospholipase A2) inhibitors. A screening-hit compound from our library, (E)-3-{4-[(4-chlorophenyl)thio]-3-nitrophenyl}acrylic acid (5), was used to design a class of 3-(1-aryl-1H-indol-5-yl)propanoic acids as new small molecule inhibitors. The resultant structure-activity relationships studied using the isolated enzyme and by cell-based assays revealed that the 1-(p-O-substituted)phenyl, 3-phenylethyl, and 5-propanoic acid groups on the indole core are essential for good inhibitory activity against cPLA2α. Optimization of the p-substituents on the N1 phenyl group led to the discovery of 56n (ASB14780), which was shown to be a potent inhibitor of cPLA2α via enzyme assay, cell-based assay, and guinea pig and human whole-blood assays. It displayed oral efficacy toward mice tetradecanoyl phorbol acetate-induced ear edema and guinea pig ovalbumin-induced asthma models. Topics: Animals; Area Under Curve; Asthma; Cytosol; Dogs; Drug Design; Edema; Enzyme Inhibitors; Female; Group IV Phospholipases A2; Guinea Pigs; Haplorhini; Humans; Indoles; Male; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Models, Chemical; Molecular Structure; Ovalbumin; Propionates; Structure-Activity Relationship; Tetradecanoylphorbol Acetate; U937 Cells	2014
Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2alpha. Journal of medicinal chemistry, 2007, Mar-22, Volume: 50, Issue:6 The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A2alpha (cPLA2alpha, type IVA phospholipase) are described. Inhibitors of cPLA2alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA2alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoates; Carrageenan; Cytosol; Edema; Group IV Phospholipases A2; Humans; In Vitro Techniques; Indoles; Male; Phospholipases A; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Sulfonamides	2007

Article

Year

Design, synthesis, and biological evaluation of 3-(1-Aryl-1H-indol-5-yl)propanoic acids as new indole-based cytosolic phospholipase A2α inhibitors.

Journal of medicinal chemistry, 2014, Sep-11, Volume: 57, Issue:17

This article describes the design, synthesis, and biological evaluation of new indole-based cytosolic phospholipase A2α (cPLA2α, a group IVA phospholipase A2) inhibitors. A screening-hit compound from our library, (E)-3-{4-[(4-chlorophenyl)thio]-3-nitrophenyl}acrylic acid (5), was used to design a class of 3-(1-aryl-1H-indol-5-yl)propanoic acids as new small molecule inhibitors. The resultant structure-activity relationships studied using the isolated enzyme and by cell-based assays revealed that the 1-(p-O-substituted)phenyl, 3-phenylethyl, and 5-propanoic acid groups on the indole core are essential for good inhibitory activity against cPLA2α. Optimization of the p-substituents on the N1 phenyl group led to the discovery of 56n (ASB14780), which was shown to be a potent inhibitor of cPLA2α via enzyme assay, cell-based assay, and guinea pig and human whole-blood assays. It displayed oral efficacy toward mice tetradecanoyl phorbol acetate-induced ear edema and guinea pig ovalbumin-induced asthma models.

Topics: Animals; Area Under Curve; Asthma; Cytosol; Dogs; Drug Design; Edema; Enzyme Inhibitors; Female; Group IV Phospholipases A2; Guinea Pigs; Haplorhini; Humans; Indoles; Male; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Models, Chemical; Molecular Structure; Ovalbumin; Propionates; Structure-Activity Relationship; Tetradecanoylphorbol Acetate; U937 Cells

2014

Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2alpha.

Journal of medicinal chemistry, 2007, Mar-22, Volume: 50, Issue:6

The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A2alpha (cPLA2alpha, type IVA phospholipase) are described. Inhibitors of cPLA2alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA2alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoates; Carrageenan; Cytosol; Edema; Group IV Phospholipases A2; Humans; In Vitro Techniques; Indoles; Male; Phospholipases A; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Sulfonamides

2007