Cyclopentane-based human NK1 antagonists. Part 1: discovery and initial SAR.

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Finke PE, Meurer LC, Levorse DA, Mills SG, Maccoss M, Sadowski S, Cascieri MA, Tsao KL, Chicchi GG, Metzger JM, Macintyre DE

Cyclopentane-based human NK1 antagonists. Part 1: discovery and initial SAR.

Bioorg Med Chem Lett. 2006 Sep 1;16(17):4497-503. Epub 2006 Jul 7.

PubMed ID

16824752 [ View in PubMed

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Abstract

An initial investigation of the novel cyclopentane scaffold 6 afforded low nanomolar human NK1 antagonists having enhanced water solubility properties compared to morpholine 1. A synthesis of this cyclopentane scaffold, having three contiguous chiral centers, and the unexpected determination that the 1,2-trans-2,3-trans-ring stereochemistry, as opposed to the cis-ether/phenyl configuration of the known structures 1-5, is optimal for this class of antagonist are described.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Aprepitant	Neurokinin 1 receptor	IC 50 (nM)	0.09	N/A	N/A	Details