title: The identification of potent, orally bioavailable tricyclic CGRP receptor antagonists.
abstract: A series of tricyclic CGRP receptor antagonists was optimized in order to improve oral bioavailability. Attenuation of polar surface area and incorporation of a weakly basic indoline nitrogen led to compound 5, a potent antagonist with good oral bioavailability in three species.
authors: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. ian_bell@merck.com
authors: Ian M
authors: IM
authors: Bell
authors: Rodney A
authors: RA
authors: Bednar
authors: Halea A
authors: HA
authors: Corcoran
authors: John F
authors: JF
authors: Fay
authors: Steven N
authors: SN
authors: Gallicchio
authors: Victor K
authors: VK
authors: Johnston
authors: James C
authors: JC
authors: Hershey
authors: Cynthia M
authors: CM
authors: Miller-Stein
authors: Eric L
authors: EL
authors: Moore
authors: Scott D
authors: SD
authors: Mosser
authors: Shane A
authors: SA
authors: Roller
authors: Christopher A
authors: CA
authors: Salvatore
authors: Cory R
authors: CR
authors: Theberge
authors: Bradley K
authors: BK
authors: Wong
authors: C
authors: C
authors: Blair Zartman
authors: Stefanie A
authors: SA
authors: Kane
authors: Theresa M
authors: TM
authors: Williams
authors: Samuel L
authors: SL
authors: Graham
authors: Joseph P
authors: JP
authors: Vacca
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002460:Cell Line; D004285:Dogs; D000882:Haplorhini; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D051381:Rats; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D013141:Spiro Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D006575:Heterocyclic Compounds, 3-Ring; D018015:Receptors, Calcitonin Gene-Related Peptide; D013141:Spiro Compounds