Keith Hopkinson Gibson

Studies leading to the identification of ZD1839 (iressa™): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer

This paper describes the development of the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 from a lead series of 4-anilinoquinazoline compounds. ZD1839 has suitable properties for use as a clinically effective drug and shows activity against human tumours. In particular, the use of pharmacokinetic data in the development of ZD1839 is discussed.

Epidermal growth factor receptor tyrosine kinase : Structure-activity relationships and antitumour activity of novel quinazolines

Abstract Investigation of structure-activity relationships of novel quinazolines has identified a 4-(4-iso-quinolylamino)-quinazoline and a 4-(trans-2-phenylcyclopropylamino)-quinazoline as potent inhibitors of EGF-receptor tyrosine kinase in vitro. Further modifications of the latter compound have identified a derivative which shows anti-tumour activity against a tumour xenograft model when dosed orally once per day.

The synthesis of heterosubstituted benzimidazole derivatives with potent angiotensin II antagonist activity

The syntheses and biological activities of novel imidazo[4,5-d]pyridazine and imidazo[4,5-c] pyridone derivatives are reported. These series include analogues which have in vitro and in vivo Angiotensin II antagonist activities which are amongst the most potent yet recorded.