395679-53-5

MCH R1 receptor

SB-568849 is a selective SLC-1 antagonist with a pK _i of 7.7 as determined in radioligand binding displacement assays; coincubation of tissue with 1 μM SB-568849 for 45 min completely inhibits the MCH induced increase in corticotropin-releasing factor (CRF) release to basal levels without causing any effect on its own. The only reported MCH receptor in the rat is SLC-1, a G protein coupled receptor found throughout the brain and periphery.

SB-568849 (Compound 15h) possesses good receptor affinity and selectivity. SB-568849 proves to be an antagonist with stability in vivo, an acceptable brain–blood ratio and oral bioavailability. SB-568849 retains affinity, demonstrates greater in vivo stability (CL _b =16 mL/min/kg) and shows an acceptable brain-blood ratio of 1. SB-568849 also shows >30-fold selectivity over a wide range of monoamine receptors and is an antagonist in the FLIPR assay with a pK _b of 7.7.