296270-64-9Relevant academic research and scientific papers
Discovery of Lu AA33810: A highly selective and potent NPY5 antagonist with in vivo efficacy in a model of mood disorder
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
, p. 5436 - 5441 (2011/10/12)
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 ([cPP1-7,NPY19-23,Ala 31,Aib32,Gln34]-hPP). In addition, ip administration of Lu AA33810 (10 mg/kg) produced antidepressant-like effects in a rat model of chronic mild stress.
5-(20-Pyridyl)-2-aminothiazoles: Alkyl amino sulfonamides and sulfamides as potent NPY5 antagonists
Packiarajan, Mathivanan,Coate, Heather,Desai, Mahesh,Jimenez, Hermogenes N.,Reinhard, Emily J.,Jubian, Vrej J.,Marzabadi, Mohammad R.,Chandrasena, Gamini,Wolinski, Toni C.,Walker, Mary W.,Andersen, Kim
, p. 6500 - 6504 (2011/12/04)
Synthesis, SAR and physico-chemical properties of an alkyl aminothiazole series 8 and 16are described. 2-Pyridylaminothiazole based compounds such as 8c and 16a exhibit high affinity at the NPY5 receptor with desirable cLogPs and solubilities. However, they also suffer fromhigh in vitro and in vivo clearance. Compound 16a partially inhibits the feeding behavior elicited by i.c.v. injection of the selective NPY5 agonist [cPP1-7, NPY19-23, Ala31, Aib32, Gln34]-human pancreatic polypeptide polypeptide (cPP).
