Amino-substituted heterocycles as isosteres of trans-cinnamides: design and synthesis of heterocyclic biaryl sulfides as potent antagonists of LFA-1/ICAM-1 binding

Gary T Wang; Sheldon Wang; Robert Gentles; Thomas Sowin; Sandra Leitza; Edward B Reilly; Thomas W von Geldern

doi:10.1016/j.bmcl.2004.10.008

Amino-substituted heterocycles as isosteres of trans-cinnamides: design and synthesis of heterocyclic biaryl sulfides as potent antagonists of LFA-1/ICAM-1 binding

Bioorg Med Chem Lett. 2005 Jan 3;15(1):195-201. doi: 10.1016/j.bmcl.2004.10.008.

Authors

Gary T Wang¹, Sheldon Wang, Robert Gentles, Thomas Sowin, Sandra Leitza, Edward B Reilly, Thomas W von Geldern

Affiliation

¹ Global Pharmaceutical Research & Development, Abbott Laboratories, Abbott Park Road, Abbott Park, IL 60064, USA. gary.t.wang@abbott.com

PMID: 15582439
DOI: 10.1016/j.bmcl.2004.10.008

Abstract

2-Amino-4-phenyl pyridine and, to a lesser extent, 4-amino-6-phenyl pyrimidine, were established as isosteres of trans-cinnamide moiety. Applying this isosterism to previously reported p-arylthio cinnamides resulted in the identification of 4-amino-6-(p-arylthio)phenyl-pyrimidines and 2-amino-4-(p-arylthio)phenyl-pyridines as potent antagonists of LFA-1/ICAM-1 binding.

MeSH terms

Amides / chemistry
Amines / chemistry*
Cell Line
Cinnamates / chemistry*
Heterocyclic Compounds / chemical synthesis
Heterocyclic Compounds / chemistry*
Heterocyclic Compounds / pharmacology*
Intercellular Adhesion Molecule-1 / drug effects*
Intercellular Adhesion Molecule-1 / metabolism
Lymphocyte Function-Associated Antigen-1 / drug effects*
Lymphocyte Function-Associated Antigen-1 / metabolism
Protein Binding

Substances

Amides
Amines
Cinnamates
Heterocyclic Compounds
Lymphocyte Function-Associated Antigen-1
Intercellular Adhesion Molecule-1
cinnamic acid