Preclinical development of a treatment for systemic lupus erythematosus

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2014
Thesis identifier
  • T16082
Person Identifier (Local)
  • 201292536
Qualification Level
Qualification Name
Department, School or Faculty
  • Janus Kinase 1 (JAK1) inhibitor 1 is being developed between GlaxoSmithKline (GSK) and Galapagos for the treatment of systemic lupus erythematosus (SLE). The medicinal chemistry route to 1 has been scaled up to provide kilogram quantities of 1 for clinical trials. A new sustainable route to 1 is required to fund larger clinical studies and enable commercial manufacture. A new route was identified to prepare 1 using a Suzuki-Miyaura coupling in the final synthetic step. For the new route to be carried out in the pilot plant, it was necessary to develop the final synthetic step to control palladium and impurity levels in order for 1 to be prepared in acceptable quality for clinical use. The new Suzuki-Miyaura coupling has been scaled up using an 45 Kg input of 149 preparing a total of 165 Kg 1 containing <10ppm Pd and all impurities within specification. Metabolism of drug substance 1 has been investigated in order to develop 1 into a medicine. The synthesis of metabolites 157 and 167 was carried out to provide analytical markers for a clinical study.
Advisor / supervisor
  • Tomkinson, Nicholas
Resource Type
  • Previously held under moratorium in Chemistry department (GSK) from 15 November 2014 until 18 June 2021.
  • The confidentiality statement on each page of this thesis DOES NOT apply