title: Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists I.
abstract: A knowledge-based design strategy led to the discovery of several new series of potent and orally bioavailable CRTh2 antagonists where a bicyclic heteroaromatic ring serves as the central core. Structure-kinetic relationships (SKR) opened up the possibility of long receptor residence times.
authors.affiliation: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Alonso
authors.affiliation: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Andrés
authors.affiliation: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Bravo
authors.affiliation: Drug Discovery Division, 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: Drug Discovery Division, 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: Drug Discovery Division, 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: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain. Electronic address: paul.eastwood@almirall.com.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Eastwood
authors.affiliation: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Peter
authors.initials: P
authors.lastname: Eichhorn
authors.affiliation: Drug Discovery Division, 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: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gómez
authors.affiliation: Drug Discovery Division, 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: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Mir
authors.affiliation: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Petit
authors.affiliation: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Roberts
authors.affiliation: Drug Discovery Division, 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: Drug Discovery Division, 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: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Vilaseca
authors.affiliation: Drug Discovery Division, Almirall R&D Centre, Laureano Miró, 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Zanuy
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000085:Acetates; D001643:Bridged Bicyclo Compounds; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor
keywords: CRTh2 antagonist; Receptor residence time; Structure–activity relationship (SAR); Structure–kinetic relationship (SKR)