2,4,6-trisubstituted triazines as protein a mimetics for the treatment of autoimmune diseases.
A first-in-class series of low molecular weight trisubstituted triazines were synthesized and evaluated for their ability to mimic protein A binding to human IgG antibody. The structure-activity relationship (SAR) demonstrates that the 1,3-phenylenediamine component was essential for robust activity. Twenty-two compounds, represented by lead molecule 34, displayed significant activity compared to protein A. These compounds may prove useful for the treatment of autoimmune disease.
Zacharie
Boulos
B
ProMetic BioSciences Inc., 500 Boulevard Cartier Ouest, Bureau 150, Laval, Québec H7V 5B7, Canada. b.zacharie@prometic.com
Abbott
Shaun D
SD
Bienvenu
Jean-François
JF
Cameron
Alan D
AD
Cloutier
Josée
J
Duceppe
Jean-Simon
JS
Ezzitouni
Abdallah
A
Fortin
Daniel
D
Houde
Karine
K
Lauzon
Caroline
C
Moreau
Nancie
N
Perron
Valérie
V
Wilb
Nicole
N
Asselin
Michel
M
Doucet
André
A
Fafard
Marie-Eve
ME
Gaudreau
Dannyck
D
Grouix
Brigitte
B
Sarra-Bournet
François
F
St-Amant
Natalie
N
Gagnon
Lyne
L
Penney
Christopher L
CL
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology / Q000378:metabolism; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D013205:Staphylococcal Protein A / Q000276:immunology / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D014227:Triazines