NBI-30545 is a potent corticotropin-releasing factor-1 antagonist with sufficient lipophilicity and water solubility for the treatment of stress disorders.
Cytosolic phospholipase A2α (cPLA2α) specifically catalyzes the hydrolysis of arachidonic acid from thesn-2-ester position of membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins and leukotrienes, both important mediators of the inflammatory process.1CAY10641 is an inactive alcohol derivative of a highly potent (IC50= 12 nM) cPLA2α inhibitor.2The parent compound demonstrates strong anti-inflammatory effects when applied topically at a dose of 0.1 mg ear in a mouse model of acute irritant contact dermatitis.2CAY10641 is rapidly cleared from the blood stream (only 0.5 μg ml remains 30 minutes after 10 mg kg intravenous administration to mice).2However, no other biological effects have been reported. 1.Schaloske, R.H., and Dennis, E.A.The phospholipase A2 superfamily and its group numbering systemBiochemica et Biophysica Acta17611246-1259(2006) 2.Drews, A., Bovens, S., Roebrock, K., et al.1-(5-carboxyindol-1-yl)propan-2-one inhibitors of human cytosolic phospholipase A2α with reduced lipophilicity: Synthesis, biological activity, metabolic stability, solubility, bioavailability, and topical in vivo activityJournal of Medicinal Chemistry535165-5178(2010)
AZD6642 is a potential and selective 5-Lipoxygenase activating Protein (FLAP) inhibitor. AZD6642 shows high specific potency and low lipophilicity resulting in a selective and metabolically stable profile. Based on initial PK PD relations a low dose to human was predicted.