Kevin Dinnell

2-Aryl Indole NK1 receptor antagonists: optimisation of indole substitution

The synthesis and biological evaluation of a series of 2-aryl indoles with high affinity for the human neurokinin-1 (hNK1) receptor are reported, concentrating on optimisation of the indole substitution.

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

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.

A convenient method for the preparation of aryl cyclopropyl ethers from phenols

Abstract A general method for the synthesis of cyclopropyl ethers from phenols is described. Alkylation of a phenol using 1-iodo-1-(phenylthio)cyclopropane followed by removal of the phenylthio group furnishes the cyclopropyl ethers in modest to excellent yields. The procedure tolerates a wide range of functional groups.

4,4-Disubstituted cyclohexylamine NK1 receptor antagonists II

Abstract 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.