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Substituted N-(3,5-Dichlorobenzenesulfonyl)-l-prolyl-phenylalanine analogues as potent VLA-4 antagonists
- Source :
- Bioorganic & Medicinal Chemistry Letters. 12:637-640
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and alpha-methyl-L-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50 approximately 1 nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series.
- Subjects :
- Metabolic Clearance Rate
Stereochemistry
Phenylalanine
Clinical Biochemistry
Biological Availability
Vascular Cell Adhesion Molecule-1
Pharmaceutical Science
Peptide
Integrin alpha4beta1
Ring (chemistry)
Biochemistry
Chemical synthesis
Rats, Sprague-Dawley
Inhibitory Concentration 50
Structure-Activity Relationship
chemistry.chemical_compound
Dogs
Drug Discovery
Animals
Structure–activity relationship
Sulfones
Molecular Biology
IC50
chemistry.chemical_classification
Sheep
Dipeptide
Organic Chemistry
Dipeptides
Haplorhini
Rats
chemistry
Polar effect
Molecular Medicine
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....63055d86099dad6304a5f734a44d503d
- Full Text :
- https://doi.org/10.1016/s0960-894x(01)00821-6