title: Tricyclic aminopyrimidine histamine H4 receptor antagonists.
abstract: This report discloses the development of a series of tricyclic histamine H(4) receptor antagonists. Starting with a low nanomolar benzofuranopyrimidine HTS hit devoid of pharmaceutically acceptable properties, we navigated issues with metabolism and solubility to furnish a potent, stable and water soluble tricyclic histamine H(4) receptor antagonist with desirable physiochemical parameters which demonstrated efficacy a mouse ova model.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, LLC 3210 Merryfield Row, San Diego, CA 92121, USA. bsavall@its.jnj.com
authors.forename: Brad M
authors.initials: BM
authors.lastname: Savall
authors.forename: Laurent
authors.initials: L
authors.lastname: Gomez
authors.forename: Frank
authors.initials: F
authors.lastname: Chavez
authors.forename: Michael
authors.initials: M
authors.lastname: Curtis
authors.forename: Steven P
authors.initials: SP
authors.lastname: Meduna
authors.forename: Aaron
authors.initials: A
authors.lastname: Kearney
authors.forename: Paul
authors.initials: P
authors.lastname: Dunford
authors.forename: Jeffery
authors.initials: J
authors.lastname: Cowden
authors.forename: Robin L
authors.initials: RL
authors.lastname: Thurmond
authors.forename: Cheryl
authors.initials: C
authors.lastname: Grice
authors.forename: James P
authors.initials: JP
authors.lastname: Edwards
mesh_terms: D000818:Animals; D006633:Histamine Antagonists / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4
chemical_list: D006633:Histamine Antagonists; C498829:Hrh4 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4