The reversed binding of beta-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors.

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Nordhoff S, Cerezo-Galvez S, Feurer A, Hill O, Matassa VG, Metz G, Rummey C, Thiemann M, Edwards PJ

The reversed binding of beta-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors.

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1744-8. Epub 2006 Jan 11.

PubMed ID
16376544 [ View in PubMed
]
Abstract

The co-crystal structure of beta-phenethylamine fragment inhibitor 5 bound to DPP-IV revealed that the phenyl ring occupied the proline pocket of the enzyme. This finding provided the basis for a general hypothesis of a reverse binding mode for beta-phenethylamine-based DPP-IV inhibitors. Novel inhibitor design concepts that obviate substrate-like structure-activity relationships (SAR) were thereby enabled, and novel, potent inhibitors were discovered.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(S)-2-[(R)-3-amino-4-(2-fluorophenyl)butyryl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamideDipeptidyl peptidase 4IC 50 (nM)237.425Details
1-(1-phenylcyclopentyl)methylamineDipeptidyl peptidase 4IC 50 (nM)330007.425Details
N-({(2S)-1-[(3R)-3-AMINO-4-(2-FLUOROPHENYL)BUTANOYL]PYRROLIDIN-2-YL}METHYL)BENZAMIDEDipeptidyl peptidase 4IC 50 (nM)907.425Details