title: Lead optimisation of pyrazoles as novel FPR1 antagonists.
abstract: Optimisation of a series of pyrazole inhibitors of the human FPR1 receptor has been achieved. The use of an in vitro media loss assay was utilised to identify sub-series with more robust DMPK profiles. These were subsequently improved to generate analogues with attractive overall profiles.
authors.affiliation: Chemistry Department, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. andymorley@live.com
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Morley
authors.forename: Sarah
authors.initials: S
authors.lastname: King
authors.forename: Bryan
authors.initials: B
authors.lastname: Roberts
authors.forename: Sarah
authors.initials: S
authors.lastname: Lever
authors.forename: Barry
authors.initials: B
authors.lastname: Teobald
authors.forename: Adrian
authors.initials: A
authors.lastname: Fisher
authors.forename: Tony
authors.initials: T
authors.lastname: Cook
authors.forename: Beth
authors.initials: B
authors.lastname: Parker
authors.forename: Mark
authors.initials: M
authors.lastname: Wenlock
authors.forename: Caroline
authors.initials: C
authors.lastname: Phillips
authors.forename: Ken
authors.initials: K
authors.lastname: Grime
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002627:Chemistry, Physical / Q000379:methods; D015195:Drug Design; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C469986:FPR1 protein, human; D011720:Pyrazoles; D044042:Receptors, Formyl Peptide