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Potent and systemically active aminopeptidase N inhibitors designed from active-site investigation

Cite this: J. Med. Chem. 1992, 35, 7, 1259–1266
Publication Date (Print):April 1, 1992
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    Cited By

    This article is cited by 77 publications.

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    7. Huixiong Chen,, Florence Noble,, Aurélie Mothé,, Hervé Meudal,, Pascale Coric,, Sophie Danascimento,, Bernard P. Roques,, Pascal George, and, Marie-Claude Fournié-Zaluski. Phosphinic Derivatives as New Dual Enkephalin-Degrading Enzyme Inhibitors: Synthesis, Biological Properties, and Antinociceptive Activities. Journal of Medicinal Chemistry 2000, 43 (7) , 1398-1408.
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    15. Reda Hmazzou, Yannick Marc, Adrien Flahault, Romain Gerbier, Nadia De Mota, Catherine Llorens-Cortes. Brain ACE2 activation following brain aminopeptidase A blockade by firibastat in salt-dependent hypertension. Clinical Science 2021, 135 (6) , 775-791.
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    58. Marie-Claude Fournié-Zaluski, Bernard P. Roques. New Selective Aminopeptidase N Inhibitors as Potential Therapeutics. 2002, 51-94.
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    61. Annabelle Reaux, Marie Claude Fournie-Zaluski, Christelle David, Sylvie Zini, Bernard P. Roques, Pierre Corvol, Catherine Llorens-Cortes. Aminopeptidase A inhibitors as potential central antihypertensive agents. Proceedings of the National Academy of Sciences 1999, 96 (23) , 13415-13420.
    62. Huixiong Chen, Bernard P. Roques, Marie-Claude Fournié-Zaluski. Design of the first highly potent and selective aminopeptidase N (EC inhibitor. Bioorganic & Medicinal Chemistry Letters 1999, 9 (11) , 1511-1516.
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    64. Tu-Cai Zheng, Maureen Burkart, David E. Richardson. A general and mild synthesis of thioesters and thiols from halides. Tetrahedron Letters 1999, 40 (4) , 603-606.
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    66. Dominique Chansel, Stanislas Czekalski, Sophie Vandermeersch, Emmanuel Ruffet, Marie-Claude Fournié-Zaluski, Raymond Ardaillou. Characterization of angiotensin IV-degrading enzymes and receptors on rat mesangial cells. American Journal of Physiology-Renal Physiology 1998, 275 (4) , F535-F542.
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    68. Raymond Ardaillou, Dominique Chansel. Synthesis and effects of active fragments of angiotensin II. Kidney International 1997, 52 (6) , 1458-1468.
    69. Mohammed Sajid, Richard E Isaac, Ian D Harrow. Purification and properties of a membrane aminopeptidase from Ascaris suum muscle that degrades neuropeptides AF1 and AF2. Molecular and Biochemical Parasitology 1997, 89 (2) , 225-234.
    70. Bradley D. Anderson. Prodrugs for improved CNS delivery. Advanced Drug Delivery Reviews 1996, 19 (2) , 171-202.
    71. Reza Oliyai. Prodrugs of peptides and peptidomimetics for improved formulation and delivery. Advanced Drug Delivery Reviews 1996, 19 (2) , 275-286.
    72. Martine Migaud, Christiane Durieux, Jason Viereck, Evelyne Soroca-Lucas, Marie-Claude Fournié-Zaluski, Bernard P. Roques. The in vivo metabolism of cholecystokinin (CCK-8) is essentially ensured by aminopeptidase A. Peptides 1996, 17 (4) , 601-607.
    73. Bernard P. ROQUES, Christiane GARBAY, Fabrice CORNILLE, Hugues de ROCQUIGNY, Armand BLOMMAERT, Marie-Claude FOURNIE-ZALUSKI. RATIONAL DRUG DESIGN BASED ON TARGET STRUCTURE ANALOGIES AND MOLECULAR BIOLOGY STUDIES. European Journal of Medicinal Chemistry 1995, 30 , 51s-66s.
    74. . Metallopeptidase (ACE, Enkephalinase and Atriopeptidase) Inhibitors. 1993, 524-581.
    75. A. Patel, H.J. Smith, R.D.E. Sewell. 6 Inhibitors of Enkephalin-degrading Enzymes as Potential Therapeutic Agents. 1993, 327-378.
    76. Florence Noble, Serge Turcaud, Marie-Claude Fournié-Zaluski, Bernard P. Roques. Repeated systemic administration of the mixed inhibitor of enkephalin-degrading enzymes, RB101, does not induce either antinociceptive tolerance or cross-tolerance with morphine. European Journal of Pharmacology 1992, 223 (1) , 83-89.
    77. Bradley D. Anderson. Prodrug Approaches for Drug Delivery to the Brain. , 573-651.

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