Synthesis and structure-activity relationships of 8-azabicyclo[3.2.1]octane benzylamine NK1 antagonists.
A series of 8-azabicyclo[3.2.1]octane amine hNK1 antagonists has been investigated and structure-activity relationships of the benzylamine and 6-exo substituents described. Acidic substituents at C6 give a series of high affinity compounds for hNK1 with selectivity over the hERG channel.
Thomson
Christopher G
CG
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. christopher_thomson@merck.com
Carlson
Emma
E
Chicchi
Gary G
GG
Kulagowski
Janusz J
JJ
Kurtz
Marc M
MM
Swain
Christopher J
CJ
Tsao
Kwei-Lan C
KL
Wheeldon
Alan
A
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008968:Molecular Conformation; D064729:Neurokinin-1 Receptor Antagonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C509738:8-azabicyclo(3.2.1)octane benzylamine; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D064729:Neurokinin-1 Receptor Antagonists