title: Synthesis and evaluation of novel tricyclic benzo[4.5]cyclohepta[1.2]pyridine derivatives as NMDA/NR2B antagonists.
abstract: A novel series of annulated tricyclic compounds was synthesized and evaluated as NMDA/NR2B antagonists. Structure-activity development was directed towards in vitro optimization of NR2B activity and selectivity over the hERG K(+) channel. Preferred compounds were subsequently evaluated for selectivity in an alpha(1)-adrenergic receptor binding counter-screen and a cell-based assay of NR2B activity.
authors: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. cjmcintyc@yahoo.com
authors: Charles J
authors: CJ
authors: McIntyre
authors: John A
authors: JA
authors: McCauley
authors: Bohumil
authors: B
authors: Bednar
authors: Rodney A
authors: RA
authors: Bednar
authors: John W
authors: JW
authors: Butcher
authors: David A
authors: DA
authors: Claremon
authors: Michael E
authors: ME
authors: Cunningham
authors: Roger M
authors: RM
authors: Freidinger
authors: Stanley L
authors: SL
authors: Gaul
authors: Carl F
authors: CF
authors: Homnick
authors: Ken S
authors: KS
authors: Koblan
authors: Scott D
authors: SD
authors: Mosser
authors: Joseph J
authors: JJ
authors: Romano
authors: Nigel J
authors: NJ
authors: Liverton
mesh_terms: D001567:Benzocycloheptenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006801:Humans; D018377:Neurotransmitter Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001567:Benzocycloheptenes; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; C121001:NR2B NMDA receptor; D018377:Neurotransmitter Agents; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate