title: Discovery of orally bioavailable NK1 receptor antagonists.
abstract: Benzyloxyphenethylpiperazines are a new class of high affinity NK1 receptor antagonists. Oral bioavailability and selectivity can be fine tuned by the nature of the substituents on the basic nitrogen atom. Addition of substituents with a carboxylic acid group led to very selective and orally active NK1 antagonists free of interaction with L-type calcium channels.
authors.affiliation: Chemistry Department, UCB Pharma, Chemin du Foriest, B-1420, Braine-l'Alleud, Belgium. christophe.genicot@ucb-group.com
authors.forename: C
authors.initials: C
authors.lastname: Genicot
authors.forename: B
authors.initials: B
authors.lastname: Christophe
authors.forename: P
authors.initials: P
authors.lastname: Collart
authors.forename: M
authors.initials: M
authors.lastname: Gillard
authors.forename: L
authors.initials: L
authors.lastname: Goossens
authors.forename: J-P
authors.initials: JP
authors.lastname: Hénichart
authors.forename: M-A
authors.initials: MA
authors.lastname: Lassoie
authors.forename: F
authors.initials: F
authors.lastname: Moureau
authors.forename: M
authors.initials: M
authors.lastname: Neuwels
authors.forename: J-M
authors.initials: JM
authors.lastname: Nicolas
authors.forename: P
authors.initials: P
authors.lastname: Pasau
authors.forename: L
authors.initials: L
authors.lastname: Quéré
authors.forename: T
authors.initials: T
authors.lastname: Ryckmans
authors.forename: F
authors.initials: F
authors.lastname: Stiernet
authors.forename: T
authors.initials: T
authors.lastname: Taverne
authors.forename: B J
authors.initials: BJ
authors.lastname: Van Keulen
mesh_terms: D000215:Acylation; D000478:Alkylation; D000818:Animals; D001682:Biological Availability; D016466:CHO Cells; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D018360:Crystallography, X-Ray; D006168:Guinea Pigs; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D064729:Neurokinin-1 Receptor Antagonists; D009584:Nitrogen; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D007202:Indicators and Reagents; D064729:Neurokinin-1 Receptor Antagonists; D010879:Piperazines; D009584:Nitrogen