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Structure-activity relationship of ortho- and meta-phenol based LFA-1 ICAM inhibitors.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2008 Oct 01; Vol. 18 (19), pp. 5245-8. Date of Electronic Publication: 2008 Aug 22. - Publication Year :
- 2008
-
Abstract
- LFA-1 ICAM inhibitors based on ortho- and meta-phenol templates were designed and synthesized by Mitsunobu chemistry. The selection of targets was guided by X-ray co-crystal data, and led to compounds which showed an up to 30-fold increase in potency over reference compound 1 in the LFA-1/ICAM1-Ig assay. The most active compound exploited a new hydrogen bond to the I-domain and exhibited subnanomolar potency.
- Subjects :
- Animals
Combinatorial Chemistry Techniques
Crystallography, X-Ray
Drug Design
Male
Molecular Conformation
Phenols chemistry
Phenols pharmacology
Rats
Stereoisomerism
Structure-Activity Relationship
Tyrosine chemistry
Intercellular Adhesion Molecule-1 drug effects
Lymphocyte Function-Associated Antigen-1 drug effects
Phenols chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 18
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 18783948
- Full Text :
- https://doi.org/10.1016/j.bmcl.2008.08.062