Piperidine-renin inhibitors compounds with improved physicochemical properties

Apo and Inhibitor Complex Structures of BACE (β-secretase)

“…In the complexes, Tyr75 is rotated out from underneath the flap, revealing a binding pocket for lipophilic groups. [27][28][29] Additional movement of the side-chain of Trp39 creates a deeper pocket, which is occupied by the ligands. The work has demonstrated that it is possible to design new classes of inhibitors for aspartic proteases by targeting the flap-open form of the enzymes and this has stimulated considerable interest in the literature.…”

Discovery of new renin inhibitory leads via sequential pharmacophore modeling, QSAR analysis, in silico screening and in vitro evaluation

“…Development efforts relied mainly on classical rational drug design [10,12,13] and structure-based concepts [9,11,14] with only one ligand-based exception that relied on CoMFA and CoMSIA [15]. A recent study combined docking and QSAR to attempt developing predictive model for rennin inhibitors [73].…”

Quantitative Structure-Activity Relationships of Renin Inhibitors

“…Compound 2 is a representative of a series of nonpeptidic piperidine based inhibitors of human plasma renin [16]. An X-ray crystal structure of 3 shows that protonated nitrogen of the piperidine ring is located between the two active site aspartic residues forming one hydrogen bond with each, thus fulfilling the function of the transition state isosteres present in other inhibitors [17].…”