title: Amine-constrained pyridazinone histamine H₃ receptor antagonists.
abstract: Pyridazinone 1 was recently reported as a potent H(3)R antagonist with good drug-like properties and in vivo activity. A series of constrained amine analogs of 1 was synthesized to identify compounds with improved pharmacokinetic profiles. From these efforts, a new class of (S)-2-pyrrolidin-1-ylmethyl-1-pyrrolidinyl amides was identified.
authors.affiliation: Discovery Research, Cephalon Inc., 145 Brandywine Parkway, West Chester, PA 19380, United States. bsundar@cephalon.com
authors.forename: Babu G
authors.initials: BG
authors.lastname: Sundar
authors.forename: Thomas
authors.initials: T
authors.lastname: Bailey
authors.forename: Edward
authors.initials: E
authors.lastname: Bacon
authors.forename: Lisa
authors.initials: L
authors.lastname: Aimone
authors.forename: Zeqi
authors.initials: Z
authors.lastname: Huang
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Lyons
authors.forename: Rita
authors.initials: R
authors.lastname: Raddatz
authors.forename: Robert
authors.initials: R
authors.lastname: Hudkins
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D054828:Histamine H3 Antagonists; D011724:Pyridazines; D018100:Receptors, Histamine H3