Piperidine renin inhibitors: from leads to drug candidates


  • H.P. Maerki
  • A. Binggeli
  • B. Bittner
  • V. Bohner-Lang
  • V. Breu
  • D. Bur
  • P.H. Coassolo
  • J.P. Clozel
  • A. D'Arcy
  • H. Doebeli
  • W. Fischli
  • C.H. Funk
  • J. Foricher
  • T. Giller
  • F. Grueninger
  • A. Guenzi
  • R. Gueller
  • T. Hartung
  • G. Hirth
  • C.H. Jenny
  • M. Kansy
  • U. Klinkhammer
  • T. Lave
  • B. Lohri
  • F.C. Luft
  • E.M. Mervaala
  • D.N. Mueller
  • M. Mueller
  • F. Montavon
  • C.H. Oefner
  • C. Qiu
  • A. Reichel
  • P. Sanwald-Ducray
  • M. Scalone
  • M. Schleimer
  • R. Schmid
  • H. Treiber
  • A. Treiber
  • O. Valdenaire
  • E. Vieira
  • P. Waldmeier
  • R. Wiegand-Chou
  • M. Wilhelm
  • W. Wostl
  • M. Zell
  • R. Zell


  • Farmaco


  • Farmaco 56 (1-2): 21-27


  • Non-peptidomimetic renin inhibitors of the pipersine type represent the a novel structural class of compounds free of the drawbacks seen with peptidomimetic compounds so far. Synthetic optimization in two structural series focusing on improvement of potency, as well as on physicochemical properties and metabolic stability, has led to the identificiation of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes. In addition, 14 normalized albuminuria and kidney tissue damage in these rats when given over a period of 4 weeks. These data suggest that treatment of chronic renal failure patients with a renin inhibitor might result in a significant improvement of the disease status.