Substituted piperidines--highly potent renin inhibitors due to induced fit adaptation of the active site.

The identification, synthesis and activity of a novel class of piperidine renin inhibitors is presented. The most active compounds show activities in the picomolar range and are among the most potent renin inhibitors ever identified.

[1]  N. Hollenberg,et al.  Renal circulation and blockade of the renin-angiotensin system. Is angiotensin-converting enzyme inhibition the last word? , 1995, Hypertension.

[2]  J. Ménard,et al.  Effects of Blocking the Angiotensin II Receptor, Converting Enzyme, and Renin Activity on the Renal Hemodynamics of Normotensive Guinea Pigs , 1993, Journal of cardiovascular pharmacology.

[3]  D. Michelot Highly Stereoselective Synthesis of Acetates of Mono- and Diunsaturated Alcohols and Analogous Aldehydes, Components of Lepidopteran Sex Pheromones, using Tetrakis[triphenylphosphine]-palladium , 1983 .

[4]  N. Markandu,et al.  Maintenance of blood pressure by the renin–angiotensin system in normal man , 1981, Nature.

[5]  M. Weber,et al.  Clinical experience with the angiotensin II receptor antagonist losartan. A preliminary report. , 1992, American journal of hypertension.

[6]  F. Bigi,et al.  Modification of the nickl reaction : A general synthetic approach to 2-vinyl-2,3-dihydrobenzofurans , 1983 .

[7]  D. Dezeeuw,et al.  RENAL AND SYSTEMIC EFFECTS OF THE RENIN INHIBITOR REMIKIREN IN PATIENTS WITH ESSENTIAL-HYPERTENSION , 1995 .

[8]  A. Mann,et al.  Selective Removal of the Tert-Butoxycarbonyl Group from Secondary Amines: ZnBr2 as the Deprotecting Reagent , 1989 .

[9]  W. Kiowski,et al.  Functional and biochemical analysis of angiotensin II-forming pathways in the human heart. , 1997, Circulation research.

[10]  G. Chatellier,et al.  Blood pressure effects of acute intravenous renin or oral angiotensin converting enzyme inhibition in essential hypertension , 1994, Journal of hypertension.

[11]  B. Healy,et al.  Angiotensin II-forming pathways in normal and failing human hearts. , 1990, Circulation research.

[12]  S. Mahboobi,et al.  Synthesis of Esters of 3‐(2‐Aminoethyl)‐1H‐indole‐2‐acetic Acid and 3‐(2‐aminoethyl)‐1H‐indole‐2‐malonic acid (= 2‐[3‐(2‐aminoethyl)‐1H‐indol‐2‐yl]propanedioic acid) 4th communication on indoles, indolenines, and indolines , 1988 .

[13]  R. Gentz,et al.  Recombinant human renin produced in different expression systems: biochemical properties and 3D structure. , 1996, Protein expression and purification.

[14]  R. Luther,et al.  Immediate blood pressure effects of the renin inhibitor enalkiren and the angiotensin-converting enzyme inhibitor enalaprilat. , 1991, American heart journal.

[15]  N. Schork,et al.  Mixture Analysis of Erythrocyte Lithium‐Sodium Countertransport and Blood Pressure , 1989, Hypertension.

[16]  D. Hutchinson,et al.  The Synthesis of 1,1-Cyclopropanediylbis(phosphonic acid) , 1990 .