title: Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity.
abstract: A new class of peptidomimetic C5a receptor antagonists characterized by C-terminal amino acids with hydrophobic side chains is presented. Systematic optimization of the first hits led to JPE1375 (36), which was intensively characterized in vitro and in vivo. Compound 36 exhibits high microsomal stability and receptor specificity and is highly active in an immune complex mediated peritonitis model (reverse passive Arthus reaction) in mice.
authors.affiliation: Jerini AG, Invalidenstrasse 130, 10115 Berlin, Germany. schnatbaum@jerini.de
authors.forename: Karsten
authors.initials: K
authors.lastname: Schnatbaum
authors.forename: Elsa
authors.initials: E
authors.lastname: Locardi
authors.forename: Dirk
authors.initials: D
authors.lastname: Scharn
authors.forename: Uwe
authors.initials: U
authors.lastname: Richter
authors.forename: Heiko
authors.initials: H
authors.lastname: Hawlisch
authors.forename: Jochen
authors.initials: J
authors.lastname: Knolle
authors.forename: Thomas
authors.initials: T
authors.lastname: Polakowski
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000009:adverse effects; D004195:Disease Models, Animal; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D051379:Mice; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy*; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000936:Antigen-Antibody Complex; D009842:Oligopeptides; D044087:Receptor, Anaphylatoxin C5a