Synthesis and biological activity of new HMG-CoA reductase inhibitors. 1. Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids

  • J Med Chem. 1990 Jan;33(1):52-60. doi: 10.1021/jm00163a010.
G Beck  1 ,  K Kesseler ,  E Baader ,  W Bartmann ,  A Bergmann ,  E Granzer ,  H Jendralla ,  B von Kerekjarto ,  R Krause ,  E Paulus
Affiliations
  • 1. Hoechst AG, Frankfurt/M, West Germany.
PMID: 2296036 DOI: 10.1021/jm00163a010
Abstract

Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids 2-4 have been synthesized. Extensive exploration of structure-activity relationships led to several compounds exceeding the inhibitory activity of mevinolin (1b) on HMG-CoA reductase, both in vitro and in vivo. First clinical trials with 2i (HR 780) are in preparation.