Discovery of new C3aR ligands. Part 1: arginine derivatives.
The synthesis and in vitro binding of several new arginine-containing C3aR ligands are reported. DMPK properties and functional activities of selected compounds have been evaluated. One compound is shown to be active in an in vivo model of airway inflammation after aerosol administration.
Denonne
Frédéric
F
UCB Global Chemistry, Chemin du Foriest R4, 1420 Braine l'Alleud, Belgium. frederic.denonne@ucb-group.com
Binet
Sophie
S
Burton
Maggi
M
Collart
Philippe
P
Dipesa
Alan
A
Ganguly
Tanmoy
T
Giannaras
Alexander
A
Kumar
Seema
S
Lewis
Timothy
T
Maounis
Florence
F
Nicolas
Jean-Marie
JM
Mansley
Tamsin
T
Pasau
Patrick
P
Preda
Dorin
D
Stebbins
Karin
K
Volosov
Alexander
A
Zou
Dong
D
D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000473:pathology; D013329:Structure-Activity Relationship; D013997:Time Factors
D000336:Aerosols; D008024:Ligands; D008565:Membrane Proteins; D011951:Receptors, Complement; C085567:complement C3a receptor; D001120:Arginine; D017346:Protein Serine-Threonine Kinases