Viral proteases and phosphorodiesterase inhibitors.
A number of novel drug candidates, which are at different stages of development and various therapeutic targets, mechanisms of action and clinical data were discussed in depth. Crystallographic studies and structures of several viral proteases were outlined and described. AG7088 (Agouron Pharmaceuticals Inc) has been developed as a potent, selective human rhinovirus (HRV)3C protease inhibitor, which has now advanced to phase II trials. Vertex Pharmaceuticals Inc has also made significant progress with a series of non-reversible hepatitis C virus (HCV)inhibitors, which were synthesized by solid-phase methods. The pharmacological profile of CI1018 (Parke-Davis (France)), which is in phase I trials for the treatment of asthma, was described as well as the synthesis of potent back-up compounds, 4-oxo-1-phenyl-3,4,6,7-tetrahydro-(1,2)-diazepino[6,7,1-hi]indoles. Other phosphorodiesterase (PDE)4 inhibitors discussed include: SB207499 (SmithKline Beecham plc), now in phase III trials for chronic obstructive pulmonary disease (COPD); and, RP73401, which was in phase II trials for asthma but has been discontinued.
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Current Drugs Ltd, Middlesex House, London W1P 6LB, United Kingdom. petera@cursci.co.uk