Jason Matthew Elliott

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.

Reversed stereochemical control in the regioselective reduction of hindered diphenylphosphinoyl (Ph2PO-) ketones and enones

Reduction of α′-diphenylphosphinoyl enones (6) and crowded α-diphenylphosphinoyl ketones (4) with sodium borohydride in the presence of cerium chloride gives the otherwise difficult to obtain erythro-alcohols (5) and (7).

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.

Horner-Wittig reactions using dibenzophosphole oxides: Stereochemically controlled reduction of ketones

Abstract Reduction of ketones having an α-dibenzophosphoie-5-oxide group witin NaBH4, L-Selectride, or Superhydride gives threo Horner-Wittig intermediates and hence E -alkenes, while NaBH4/CeCl3 gives erythro intermediates and hence Z -alkenes.

Neurokinin receptor antagonists

The competitive area of neurokinin (NK) receptor antagonists has recently seen the publication of early clinical results which provide strong support for their use in the treatment of pain, emesis and asthma. Preclinical models support their use in a number of additional disorders including anxiety, arthritis, migraine, cancer and schizophrenia. New indications, such as glaucoma and ocular hypotension, neuronal injury and stroke, cardiac disorders and topical applications have recently been claimed. Published patent applications from most of the major pharmaceutical companies claim a wide variety of structural classes as antagonists at all three neurokinin receptors. This review discusses the significance of new clinical data for ongoing drug discovery efforts, and patent claims for new indications and new structural classes for the period since the last review in early 1996.

Serine derived NK1 antagonists 2: a pharmacophore model for arylsulfonamide binding

Modifications to the spirocyclic aryl sulfonamide portion of serine derived NK1 antagonists allow a partial pharmacophore model to be developed.

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.

Serine derived NK1 antagonists. 1: The effect of modifications to the serine substituents.

A series of novel serine derived NK1 antagonists is described. The effect of variations in the N-benzyl, O-benzyl and serine groups are used to define the elements which are necessary for binding.

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.

Regiospecific synthesis of enones via α-(phenylthio)-ketones: 2,5-dimethyl-4-hexen-3-one, E-6-methyl-2-hepten-4-one, E-7-methyl-4-octen-3-one, and ar-turmerone

Enones not available from aldol condensations may be synthesised regio-specifically via α-(phenylthio)ketones: the title compounds have been made by this route.