Discovery of N-(3-fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-pi peridinamine (GSK962040), the first small molecule motilin receptor agonist clinical candidate.

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Westaway SM, Brown SL, Fell SC, Johnson CN, MacPherson DT, Mitchell DJ, Myatt JW, Stanway SJ, Seal JT, Stemp G, Thompson M, Lawless K, McKay F, Muir AI, Barford JM, Cluff C, Mahmood SR, Matthews KL, Mohamed S, Smith B, Stevens AJ, Bolton VJ, Jarvie EM, Sanger GJ

Discovery of N-(3-fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-pi peridinamine (GSK962040), the first small molecule motilin receptor agonist clinical candidate.

J Med Chem. 2009 Feb 26;52(4):1180-9. doi: 10.1021/jm801332q.

PubMed ID
19191554 [ View in PubMed
]
Abstract

N-(3-fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-pi peridinamine 12 (GSK962040) is a novel small molecule motilin receptor agonist. It possesses excellent activity at the recombinant human motilin receptor and also at the native rabbit motilin receptor where its agonist activity results in potentiation of the amplitude of neuronal-mediated contractions of isolated gastric antrum tissue. Compound 12 also possesses highly promising pharmacokinetic profiles in both rat and dog, and these results, in combination with further profiling in human native tissue and an in vivo model of gastrointestinal transit in the rabbit, have led to its selection as a candidate for further development.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ErythromycinCytochrome P450 3A4IC 50 (nM)1900N/AN/ADetails
ErythromycinCytochrome P450 3A4IC 50 (nM)190N/AN/ADetails
ErythromycinMotilin receptorEC 50 (nM)50.12N/AN/ADetails