Cyclopentane-based human NK1 antagonists. Part 2: development of potent, orally active, water-soluble derivatives.

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Meurer LC, Finke PE, Owens KA, Tsou NN, Ball RG, Mills SG, Maccoss M, Sadowski S, Cascieri MA, Tsao KL, Chicchi GG, Egger LA, Luell S, Metzger JM, Macintyre DE, Rupniak NM, Williams AR, Hargreaves RJ

Cyclopentane-based human NK1 antagonists. Part 2: development of potent, orally active, water-soluble derivatives.

Bioorg Med Chem Lett. 2006 Sep 1;16(17):4504-11. Epub 2006 Jul 10.

PubMed ID

16831551 [ View in PubMed

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Abstract

The synthesis and optimization of a cyclopentane-based hNK1 antagonist scaffold 3, having four chiral centers, will be discussed in the context of its enhanced water solubility properties relative to the marketed anti-emetic hNK1 antagonist EMEND (Aprepitant). Sub-nanomolar hNK1 binding was achieved and oral activity comparable to Aprepitant in two in vivo models will be 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