2-Aryl indole NK1 receptor antagonists: optimisation of the 2-aryl ring and the indole nitrogen substituent

K Dinnell; G G Chicchi; M J Dhar; J M Elliott; G J Hollingworth; M M Kurtz; M P Ridgill; W Rycroft; K L Tsao; A R Williams; C J Swain

doi:10.1016/s0960-894x(01)00183-4

2-Aryl indole NK1 receptor antagonists: optimisation of the 2-aryl ring and the indole nitrogen substituent

Bioorg Med Chem Lett. 2001 May 7;11(9):1237-40. doi: 10.1016/s0960-894x(01)00183-4.

Authors

K Dinnell¹, G G Chicchi, M J Dhar, J M Elliott, G J Hollingworth, M M Kurtz, M P Ridgill, W Rycroft, K L Tsao, A R Williams, C J Swain

Affiliation

¹ Department of Medicinal Chemistry, Merck, Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Harlow, Essex, UK. [email protected]

PMID: 11354385
DOI: 10.1016/s0960-894x(01)00183-4

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.

MeSH terms

Animals
Behavior, Animal / drug effects
Binding, Competitive / drug effects
CHO Cells
Cricetinae
Electrons
Gerbillinae
Indoles / chemical synthesis*
Indoles / pharmacokinetics
Indoles / pharmacology*
Molecular Conformation
Neurokinin-1 Receptor Antagonists*
Nitrogen / chemistry
Recombinant Proteins / drug effects
Structure-Activity Relationship
Substance P / metabolism

Substances

Indoles
Neurokinin-1 Receptor Antagonists
Recombinant Proteins
Substance P
Nitrogen