Document Report Card

ID: ALA1126141

Journal: J Med Chem

Title: Substituted 4,6-diaminoquinolines as inhibitors of C5a receptor binding.

Authors: Lanza TJ, Durette PL, Rollins T, Siciliano S, Cianciarulo DN, Kobayashi SV, Caldwell CG, Springer MS, Hagmann WK.

Abstract: The anaphylatoxin C5a is implicated in a number of inflammatory diseases. It is a highly cationic protein with 13 of 74 amino acids being either arginine or lysine. A search focusing on positively charged molecules, particularly amine-containing functionalities, led to the discovery of substituted 4,6-diaminoquinolines 1 [N,N'-bis(4-amino-2-methyl-6-quinolyl)urea] and 7 [6-N-(2-chlorocinnamoyl)-4,6-diamino-2-methylquinoline] as inhibitors of C5a receptor binding. These two compounds inhibited the binding of radiolabeled C5a to its receptor isolated from human neutrophils with IC50's = 3.3 and 12 micrograms/mL, respectively. Our efforts to enhance their potencies by chemical modification revealed a narrow profile of potency for effective C5a receptor binding inhibition.

CiteXplore: 1310118

DOI: 10.1021/jm00080a008