4,4-Disubstituted cyclohexylamine NK(1) receptor antagonists I.
A series of novel 4,4-disubstituted cyclohexylamine based NK(1) antagonists is described. The effect of changes to the C(1)-C(4) relative stereochemistry on the cyclohexane ring and replacements for the flexible linker are discussed, leading to the identification of compounds with high affinity and good in vivo duration of action.
Elliott
Jason M
JM
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. jason_elliot@merck.com
Castro
Jose L
JL
Chicchi
Gary G
GG
Cooper
Laura C
LC
Dinnell
Kevin
K
Hollingworth
Gregory J
GJ
Ridgill
Mark P
MP
Rycroft
Wayne
W
Kurtz
Marc M
MM
Shaw
Duncan E
DE
Swain
Christopher J
CJ
Tsao
Kwei-Lan
KL
Yang
Lihu
L
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005849:Gerbillinae; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D064729:Neurokinin-1 Receptor Antagonists; D011869:Radioligand Assay; D018040:Receptors, Neurokinin-1 / Q000737:chemistry; D013329:Structure-Activity Relationship
D003514:Cyclohexylamines; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1