Spirocyclic NK(1) antagonists II: [4.5]-spiroethers

Brian J Williams; Margaret A Cascieri; Gary G Chicchi; Timothy Harrison; Andrew P Owens; Simon N Owen; Nadia M J Rupniak; David F Tattersall; Angela Williams; Christopher J Swain

doi:10.1016/s0960-894x(02)00509-7

Spirocyclic NK(1) antagonists II: [4.5]-spiroethers

Bioorg Med Chem Lett. 2002 Oct 7;12(19):2719-22. doi: 10.1016/s0960-894x(02)00509-7.

Authors

Brian J Williams¹, Margaret A Cascieri, Gary G Chicchi, Timothy Harrison, Andrew P Owens, Simon N Owen, Nadia M J Rupniak, David F Tattersall, Angela Williams, Christopher J Swain

Affiliation

¹ Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, UK. [email protected]

PMID: 12217362
DOI: 10.1016/s0960-894x(02)00509-7

Abstract

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.

MeSH terms

Animals
Antiemetics / chemical synthesis
Antiemetics / pharmacology
Behavior, Animal / drug effects
Binding, Competitive / drug effects
CHO Cells
Cricetinae
Dogs
Ethers / chemical synthesis*
Ethers / pharmacology*
Ferrets
Gerbillinae
Humans
Neurokinin-1 Receptor Antagonists*
Rats
Spiro Compounds / chemical synthesis*
Spiro Compounds / pharmacology*

Substances

Antiemetics
Ethers
Neurokinin-1 Receptor Antagonists
Spiro Compounds