title: Synthesis of novel histamine H4 receptor antagonists.
abstract: This letter describes the discovery and synthesis of a series of octahydropyrrolo[3,4-c]pyrrole based selective histamine hH4 receptor antagonists. The amidine compound 20 was found to be a potent and selective histamine H4 receptor antagonist with moderate clearance and a high volume of distribution.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Sandwich, Kent CT13 9NJ, United Kingdom.
authors.forename: Charlotte A L
authors.initials: CA
authors.lastname: Lane
authors.forename: Duncan
authors.initials: D
authors.lastname: Hay
authors.forename: Charles E
authors.initials: CE
authors.lastname: Mowbray
authors.forename: Michael
authors.initials: M
authors.lastname: Paradowski
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Selby
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Swain
authors.forename: David H
authors.initials: DH
authors.lastname: Williams
mesh_terms: D000818:Animals; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D053961:Azabicyclo Compounds; C418607:HRH4 protein, human; D011759:Pyrrolidines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4