5-(2′-Pyridyl)-2-aminothiazoles: Alkyl amino sulfonamides and sulfamides as potent NPY5 antagonists

Synthesis, SAR and physico-chemical properties of an alkyl aminothiazole series 8 and 16 are described. 2-Pyridylaminothiazole based compounds such as 8c and 16a exhibit high affinity at the NPY5 receptor with desirable c Log Ps and solubilities. However, they also suffer from high 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).

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