Discovery of a potent and novel motilin agonist.

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Li JJ, Chao HG, Wang H, Tino JA, Lawrence RM, Ewing WR, Ma Z, Yan M, Slusarchyk D, Seethala R, Sun H, Li D, Burford NT, Stoffel RH, Salyan ME, Li CY, Witkus M, Zhao N, Rich A, Gordon DA

Discovery of a potent and novel motilin agonist.

J Med Chem. 2004 Mar 25;47(7):1704-8.

PubMed ID

15027861 [ View in PubMed

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Abstract

A novel series of dihydro- and tetrahydrotriazolopyridazine-1,3-dione-based amino acid derivatives were identified as very potent motilin receptor agonists. Incorporating one additional phenylethyl glycinamide subunit to 1 (EC(50) = 660 nM) was found to improve in vitro potency approximately 3000-fold, resulting in compound 10 (EC(50) = 0.22 nM). The more potent enantiomer 11A has an EC(50) of 0.047 nM in the motilin receptor functional assay and a K(i) of 0.7 nM in the binding assay. In addition, compound 11A was shown to have a significantly reduced tendency to cause receptor desensitization as compared with the motilin receptor agonist ABT-229.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Erythromycin	Motilin receptor	EC 50 (nM)	400	N/A	N/A	Details
Erythromycin	Motilin receptor	Ki (nM)	37000	N/A	N/A	Details