Piperidine renin inhibitors: from leads to drug candidates
| Autor: | Maerki Hans-Peter, Michelangelo Scalone, Joseph Foricher, Allan D'Arcy, Greg Hirth, Maurice Wilhelm, Christian Oefner, Fiona Grüninger, Thomas Giller, P Sanwald-Ducray, R Zell, Jean-Paul Clozel, Marcel Muller, E M Mervaala, Thomas Hartung, Friedrich C. Luft, Uwe Klinkhammer, Michael Schleimer, A. Treiber, Daniel Bur, Thierry Lavé, Walter Fischli, Rolf Güller, Heinz Stadler, Francois Montavon, Volker Breu, Beate Bittner, Alfred Binggeli, Olivier Valdenaire, H Doebeli, Philippe Coassolo, C Qiu, Wolfgang Wostl, Christoph Funk, Eric Vieira, Rudolf Schmid, Alberto Guenzi, Andreas Reichel, R Wiegand-Chou, V Bohner-Lang, Christian Jenny, Bruno Lohri, Manfred Zell, Manfred Kansy, Pius Waldmeier, Dominik N. Müller |
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| Rok vydání: | 2001 |
| Předmět: |
Drug
medicine.drug_class Peptidomimetic media_common.quotation_subject Pharmaceutical Science Blood Pressure Pharmacology Renin inhibitor Piperidines Drug Discovery Renin–angiotensin system Renin medicine Potency Animals Humans Renal Insufficiency Antihypertensive Agents media_common Kidney biology Chemistry medicine.anatomical_structure Biochemistry Enzyme inhibitor biology.protein Albuminuria medicine.symptom |
| Zdroj: | Farmaco (Societa chimica italiana : 1989). 56(1-2) |
| ISSN: | 0014-827X |
| Popis: | Non-peptidomimetic renin inhibitors of the piperidine type represent a novel structural class of compounds potentially 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 identification of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes. In addition, 14 normalizes 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. |
| Databáze: | OpenAIRE |
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