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ID: ALA1833793
Journal: Bioorg Med Chem Lett
Title: Discovery of Lu AA33810: a highly selective and potent NPY5 antagonist with in vivo efficacy in a model of mood disorder.
Authors: Packiarajan M, Marzabadi MR, Desai M, Lu Y, Noble SA, Wong WC, Jubian V, Chandrasena G, Wolinsky TD, Zhong H, Walker MW, Wiborg O, Andersen K.
Abstract: The structure-activity relationship of a series of tricyclic-sulfonamide compounds 11-32 culminating in the discovery of N-[trans-4-(4,5-dihydro-3,6-dithia-1-aza-benzo[e]azulen-2-ylamino)-cyclohexylmethyl]-methanesulfonamide (15, Lu AA33810) is reported. Compound 15 was identified as a selective and high affinity NPY5 antagonist with good oral bioavailability in mice (42%) and rats (92%). Dose dependent inhibition of feeding was observed after i.c.v. injection of the selective NPY5 agonist ([cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]-hPP). In addition, ip administration of Lu AA33810 (10 mg/kg) produced antidepressant-like effects in a rat model of chronic mild stress.
CiteXplore: 21782428