title: Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of sulphone-based CRTh2 antagonists.
abstract: Monocyclic and bicyclic ring systems were investigated as the "core" section of a series of diphenylsulphone-containing acetic acid CRTh2 receptor antagonists. A range of potencies were observed and single-digit nanomolar potencies were obtained in both the monocyclic and bicyclic cores. Residence times for the monocyclic compounds were very short. Some of the bicyclic cores displayed better residence times. A methyl group in the northern part of the core, between the head and tail was a necessary requirement for the beginnings of long residence times. Variations of the tail substitution maximised potencies and residence times.
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Buil
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Calbet
authors.affiliation: Almirall-Barcelona Science Park Unit, Barcelona Science Park, Josep Samitier 1-5, 08028 Barcelona, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Castillo
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Castro
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteve
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: Almirall-Barcelona Science Park Unit, Barcelona Science Park, Josep Samitier 1-5, 08028 Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Forns
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Jacob
authors.initials: J
authors.lastname: González
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: López
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain. Electronic address: rick.roberts@almirall.com.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Roberts
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Sevilla
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Vidal
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Vidal
authors.affiliation: Almirall R&D Centre, Laureano Miró, 408-410, 08980, Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Vilaseca
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013450:Sulfones; C036293:prostaglandin D2 receptor
keywords: CRTh2 antagonist; Receptor residence time; Structure-activity relationship (SAR); Structure-kinetic relationship (SKR)