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Updated: Oct 5, 2026

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Synthesis and structure-activity relationships of trisubstituted phenyl urea derivatives as neuropeptide Y5 receptor
C Fotsch1, J D Sonnenberg, N Chen
1Department of Small Molecule Drug Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA.
Abstract:
1-((1R,2R)-2-Hydroxy-1-methyl-2-phenylethyl)-1-methyl-3-(4-phenoxyphenyl)urea (1) was identified as a hit from the screening of the neuropeptide Y5 (NPY5) receptor. This lead was optimized for in vitro potency by changing the stereochemistry, the phenylethyl segment, the urea portion, and the 4-phenoxyphenyl group on the molecule. Over 40 analogues of 1 were prepared to study the structure-activity relationship for this series. The most potent compounds in this class have IC(50)s less than 0.1 nM at the NPY5 receptor (e.g., 40f, 44a, and 47). To determine the functional activity for this series of compounds, selected analogues were tested in a cellular assay measuring forskolin-induced cyclic AMP accumulation in 293 cells transfected with the human NPY5 receptor. All urea analogues tested in the functional assay acted as antagonists (e.g., 1, 32, 40a, and 44e).
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