title: Discovery and characterization of novel, potent, non-peptide parathyroid hormone-1 receptor antagonists.
abstract: A 1,3,4-benzotriazepine was identified as a suitable lead in our effort toward obtaining a non-peptide parathyroid hormone-1 receptor (PTH1R) antagonist. A process of optimization afforded derivatives displaying nanomolar PTH1R affinity, a representative example of which behaved as a PTH1R antagonist in cell-based cyclic adenosine monophosphate (cAMP) assays, with selectivity over PTH2 receptors.
authors.affiliation: James Black Foundation, 68 Half Moon Lane, Dulwich, London, SE24 9JE, UK. iain.mcdonald@kcl.ac.uk
authors.forename: Iain M
authors.initials: IM
authors.lastname: McDonald
authors.forename: Carol
authors.initials: C
authors.lastname: Austin
authors.forename: Ildiko M
authors.initials: IM
authors.lastname: Buck
authors.forename: David J
authors.initials: DJ
authors.lastname: Dunstone
authors.forename: John
authors.initials: J
authors.lastname: Gaffen
authors.forename: Eric
authors.initials: E
authors.lastname: Griffin
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Harper
authors.forename: Robert A D
authors.initials: RA
authors.lastname: Hull
authors.forename: S Barret
authors.initials: SB
authors.lastname: Kalindjian
authors.forename: Ian D
authors.initials: ID
authors.lastname: Linney
authors.forename: Caroline M R
authors.initials: CM
authors.lastname: Low
authors.forename: Dipa
authors.initials: D
authors.lastname: Patel
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pether
authors.forename: Michelle
authors.initials: M
authors.lastname: Raynor
authors.forename: Sonia P
authors.initials: SP
authors.lastname: Roberts
authors.forename: Mark E
authors.initials: ME
authors.lastname: Shaxted
authors.forename: John
authors.initials: J
authors.lastname: Spencer
authors.forename: Katherine I M
authors.initials: KI
authors.lastname: Steel
authors.forename: David A
authors.initials: DA
authors.lastname: Sykes
authors.forename: Paul T
authors.initials: PT
authors.lastname: Wright
authors.forename: Wei
authors.initials: W
authors.lastname: Xun
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D011869:Radioligand Assay; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D001552:Benzazepines; D044168:Receptor, Parathyroid Hormone, Type 1; D011994:Recombinant Proteins; D000242:Cyclic AMP