Discovery of Lu AA33810: A highly selective and potent NPY5 antagonist with in vivo efficacy in a model of mood disorder

M Packiarajan, MR Marzabadi, M Desai, Y Lu…

文献索引：Packiarajan, Mathivanan; Marzabadi, Mohammad R.; Desai, Mahesh; Lu, Yalei; Noble, Stewart A.; Wong, Wai C.; Jubian, Vrej; Chandrasena, Gamini; Wolinsky, Toni D.; Zhong, Hualing; Walker, Mary W.; Wiborg, Ove.; Andersen, Kim Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 18 p. 5436 - 5441

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被引用次数: 6

摘要

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 ...