The present invention relates to a series of 2,3,5-substituted pyridone derivatives of formula I: wherein R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5'-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.