Renin inhibitors molecular modeling

For a series of renin inhibitors a good correlation between the measured membrane permeability and log D was found (r2 = 0.8). The model has been validated against a human perfusion model [10], as well as being extended by including molecular weight as a third parameter [27]. A further development of the model is to chronically cannulate the animals so that they can be allowed to recover [28]. This model should avoid any effects from the anesthetic on the absorption process. 

E. A. Lunney and C. Humblet, in Medicinal Chemistry of the Renin-Angiotensin System, Pharmaco Chemistry Library, 21, P. B. M. W. M. Timmermans and R. R. Wexler, Eds., Elsevier, New York, 1994, pp. 73-101. Renin Inhibitor Design Through Molecular Modeling. 

Using this scheme, a molecular modelling method was developed, in order to substitute earlier peptide inhibitors with a compound lacking the PI—P4 spanning backbone that would optimally fit the hydrophobic surface of the large S3—SI cavity of renin Fig. 2.3 [6]. 

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