Structure-Activity Relationship of novel phenylacetic CXCR1 inhibitors.
We reported recently the Structure-Activity Relationship (SAR) of a class of CXCL8 allosteric modulators. They invariably share a 2-arylpropionic moiety so far considered a key structural determinant of the biological activity. We show the results of recent SAR studies on a novel series of phenylacetic derivatives supported by a combined approach of mutagenesis experiments and conformational analysis. The results suggest novel insights on the fine role of the propionic/acetic chain in the modulation of CXCL8 receptors.
Sablone
Manolo Rocco
MR
Research Center, Dompé pha.r.ma s.p.a., via Campo di Pile, 67100, L'Aquila, Italy.
Cesta
Maria Candida
MC
Moriconi
Alessio
A
Aramini
Andrea
A
Bizzarri
Cinzia
C
Di Giacinto
Claudia
C
Di Bitondo
Rosa
R
Gloaguen
Isabelle
I
Aschi
Massimiliano
M
Crucianelli
Marcello
M
Bertini
Riccardo
R
Allegretti
Marcello
M
D000494:Allosteric Regulation; D000495:Allosteric Site; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002633:Chemotaxis; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D016296:Mutagenesis; D009154:Mutation; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D023062:Receptors, Interleukin-8A