Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists.

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Young JR, Eid R, Turner C, DeVita RJ, Kurtz MM, Tsao KL, Chicchi GG, Wheeldon A, Carlson E, Mills SG

Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists.

Bioorg Med Chem Lett. 2007 Oct 1;17(19):5310-5. Epub 2007 Aug 16.

PubMed ID

17723300 [ View in PubMed

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Abstract

The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK(1) antagonists in vitro and efficacious in vivo with minimal interactions with P(450) liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK(1) binding affinity, functional activity, and a good PD response in vivo.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Aprepitant	Cytochrome P450 3A4	IC 50 (nM)	46	N/A	N/A	Details
Aprepitant	Neurokinin 1 receptor	IC 50 (nM)	0.09	N/A	N/A	Details