title: 2-Aryl indole NK1 receptor antagonists: optimisation of the 2-aryl ring and the indole nitrogen substituent.
abstract: Novel 2-aryl indole hNK1 receptor ligands were prepared utilising palladium cross-coupling chemistry of a late intermediate as a key step. Compounds with high hNK1 receptor binding affinity and good brain penetration (e.g., 9d) were synthesised.
authors.affiliation: Department of Medicinal Chemistry, Merck, Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Harlow, Essex, UK. kevin_dinnell@merck.com
authors.forename: K
authors.initials: K
authors.lastname: Dinnell
authors.forename: G G
authors.initials: GG
authors.lastname: Chicchi
authors.forename: M J
authors.initials: MJ
authors.lastname: Dhar
authors.forename: J M
authors.initials: JM
authors.lastname: Elliott
authors.forename: G J
authors.initials: GJ
authors.lastname: Hollingworth
authors.forename: M M
authors.initials: MM
authors.lastname: Kurtz
authors.forename: M P
authors.initials: MP
authors.lastname: Ridgill
authors.forename: W
authors.initials: W
authors.lastname: Rycroft
authors.forename: K L
authors.initials: KL
authors.lastname: Tsao
authors.forename: A R
authors.initials: AR
authors.lastname: Williams
authors.forename: C J
authors.initials: CJ
authors.lastname: Swain
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D004583:Electrons; D005849:Gerbillinae; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008968:Molecular Conformation; D064729:Neurokinin-1 Receptor Antagonists; D009584:Nitrogen / Q000737:chemistry; D011994:Recombinant Proteins / Q000187:drug effects; D013329:Structure-Activity Relationship; D013373:Substance P / Q000378:metabolism
chemical_list: D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D011994:Recombinant Proteins; D013373:Substance P; D009584:Nitrogen