The discovery of sulfonylated dipeptides as potent VLA-4 antagonists
WK Hagmann, PL Durette, T Lanza, NJ Kevin… - Bioorganic & medicinal …, 2001 - Elsevier
WK Hagmann, PL Durette, T Lanza, NJ Kevin, SE de Laszlo, IE Kopka, D Young…
Bioorganic & medicinal chemistry letters, 2001•ElsevierDirected screening of a carboxylic acid-containing combinatorial library led to the discovery
of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis
afforded a series of sulfonylated dipeptide inhibitors with structural components that when
combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for
medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted
biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic …
of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis
afforded a series of sulfonylated dipeptide inhibitors with structural components that when
combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for
medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted
biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic …
Directed screening of a carboxylic acid-containing combinatorial library led to the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic characterization of this series are presented.
Elsevier