Spirocyclic NK(1) antagonists II: [4.5]-spiroethers.
A series of novel spiroether-based neurokinin-1 (NK(1)) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration.
Williams
Brian J
BJ
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, UK. brian_williams@merck.com
Cascieri
Margaret A
MA
Chicchi
Gary G
GG
Harrison
Timothy
T
Owens
Andrew P
AP
Owen
Simon N
SN
Rupniak
Nadia M J
NM
Tattersall
David F
DF
Williams
Angela
A
Swain
Christopher J
CJ
D000818:Animals; D000932:Antiemetics / Q000138:chemical synthesis / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D004285:Dogs; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology*; D005289:Ferrets; D005849:Gerbillinae; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
D000932:Antiemetics; D004987:Ethers; D064729:Neurokinin-1 Receptor Antagonists; D013141:Spiro Compounds