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Piperidine renin inhibitors: from leads to drug candidates

Item Type:Article
Title:Piperidine renin inhibitors: from leads to drug candidates
Creators Name:Maerki, H.P. and Binggeli, A. and Bittner, B. and Bohner-Lang, V. and Breu, V. and Bur, D. and Coassolo, P.H. and Clozel, J.P. and D'Arcy, A. and Doebeli, H. and Fischli, W. and Funk, C.H. and Foricher, J. and Giller, T. and Grueninger, F. and Guenzi, A. and Gueller, R. and Hartung, T. and Hirth, G. and Jenny, C.H. and Kansy, M. and Klinkhammer, U. and Lave, T. and Lohri, B. and Luft, F.C. and Mervaala, E.M. and Mueller, D.N. and Mueller, M. and Montavon, F. and Oefner, C.H. and Qiu, C. and Reichel, A. and Sanwald-Ducray, P. and Scalone, M. and Schleimer, M. and Schmid, R. and Treiber, H. and Treiber, A. and Valdenaire, O. and Vieira, E. and Waldmeier, P. and Wiegand-Chou, R. and Wilhelm, M. and Wostl, W. and Zell, M. and Zell, R.
Abstract: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.
Keywords:Renin, Renin-Inhibitor, Aspartic Proteinase, Animals
Page Range:21-27
Date:1 March 2001
Official Publication:https://doi.org/10.1016/S0014-827X(01)01004-7
PubMed:View item in PubMed

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