Amino-substituted heterocycles as isosteres of trans-cinnamides: design and synthesis of heterocyclic biaryl sulfides as potent antagonists of LFA-1/ICAM-1 binding.
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.
Wang
Gary T
GT
Global Pharmaceutical Research & Development, Abbott Laboratories, Abbott Park Road, Abbott Park, IL 60064, USA. gary.t.wang@abbott.com
Wang
Sheldon
S
Gentles
Robert
R
Sowin
Thomas
T
Leitza
Sandra
S
Reilly
Edward B
EB
von Geldern
Thomas W
TW
D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D002460:Cell Line; D002934:Cinnamates / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding
D000577:Amides; D000588:Amines; D002934:Cinnamates; D006571:Heterocyclic Compounds; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; C029010:cinnamic acid