Renin inhibitors applications

The asymmetric hydrogenation of itaconic acid (Scheme 21) and its derivatives132 has become adopted as something of a standard by which catalysts are compared. A selection of results is given in Table 2 (e.e.s only)133,76. Further applications of related reductions include the synthesis of the Renin inhibitor subunit 12 by reduction of 13 in 95% e.e.132 and the protease inhibitor 14 by reduction of 15 in this case in up to 84% e.e.134. For these processes the ligands of choice were either BINAP (in conjunction with Ru) or a derivative of BPPM (P7). 

Interestingly, researchers at Hoffmann-La Roche reported the foundations for a similar concept applicable to aspartic proteases in 1999, identifying disubstituted piperidines as renin inhibitors (Figure 1.18) [99, 100], Also here, a cyclic disub-... 

J. S. Tokarski and A. J. Hopfinger, Prediction of ligand receptor binding thermodynamics by free energy force field (FEFF) 3D-QSAR analysis application to a set of peptidometic renin inhibitors., J. Chem. Inf. Comput. Sci., 1997, 37, 792-811. 

Kempf. D.J. (1994) Design of symmetry-based, peptidomimetic inhibitors of human immunodeHciency virus protease. Methods Enzymol.. 241. 334-354. Wood, J.M. ef al. (1994) Pharmacology of renin inhibitors and their application to the treatment of hypertension. Pharmacol. Ther, 61.325-344. 

Development, evaluation and application of 3D QSAR Pharmacophore model in the discovery of potential human renin inhibitors. BMC Bioinformatics 12 Suppl 14, S4... 

The consistency of the high levels of enantiocontrol accessible in these diazoester cyclizations is underpinned by their growing applications in enantiose-lective synthesis of bioactive molecules containing cyclopropane units. Notable examples include the preparation of multifunctional cyclopropanes as peptide isosteres for renin inhibitors (Scheme 4) [42] presqualene alcohol from farnesyl diazoacetate (Scheme 5) [43] the GABA analogue 3-azabicyclo[3.1.0]hexan-2-one from N-allyldiazoacetamide, Eq. (26) [23] and precursors of lR,3S)-cis-chrysanthemic acid and the pheromone, E-(-)-dictyopterene C (Scheme 6) [44, 45],... 

Riccioni G, Vitulano N, D Orazio N, Bellocci F. Aliskiren, the first approved renin inhibitor. Clinical application and safety in the treatment of hypertension. Adv Ther 2009 26(7) 700-10. 

Myers pseudoephedrine-based enolate alkylation was more recently applied in total syntheses of (-)-platensimycin [19] and brasilinolides [20]. By linking pseudoephedrine through the alcoholic moiety to a Merrifield resin, a polymer-bound version of Myers reagent was developed [21]. A twofold application of the pseudoephedrine-based enolate alkylation in a synthesis of Novartis orally active renin inhibitor CGP60536B demonstrates the value of this method in pharmaceutical chemistry [22]. 

Lindsay KB, Skrydstrup T. Formal total synthesis of the potent renin inhibitor aliskiren application of a SmL-promoted acyl-like radical coupling. J. Org. Chem. 2006 71(13) 4766-4777. 

The products of the phospho-aldol reaction, a-functionalised phosphonate esters such as a-hydroxy- and a-aminophosphonates, find widespread application directly or indirectly as precursors to enzyme inhibitors (such as the enzymes renin [6], thrombin [7],EPSP synthase [8], HIV protease [9] and various classes of PTK and PTPs [10]) and phosphate analogues [11], antibiotics [ 12], antiviral agents [ 13], and in nucleotide technology [ 14]. Within each application stereochemistry of the phosphonate is crucial to eliciting the required properties [15]. 

The peptidic a-hydroxyl phosphonates present a promising and structurally unique class of transition-state analogue inhibitors of proteolytic enzymes and make the first disclosure of their application in preparing inhibitors of human renin. 

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