Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2001 Oct 22;11(20):2709-13.

The discovery of sulfonylated dipeptides as potent VLA-4 antagonists.

Author information

1
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. william_hagmann@merck.com

Abstract

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.

PMID:
11591507
DOI:
10.1016/s0960-894x(01)00544-3
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center