140926-08-5Relevant academic research and scientific papers
Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides
Rosenberg,Spina,Woods,Polakowski,Martin,Yao,Stein,Cohen,Barlow,Egan,Tricarico,Baker,Kleinert
, p. 449 - 459 (2007/10/02)
A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N- terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 ± 4%) is the highest reported for any peptidic renin inhibitor.
1,2,3-Trisubstituted Cyclopropanes as Conformationally Restricted Peptide Isosteres: Application to the Design and Synthesis of Novel Renin Inhibitors
Martin, Stephen F.,Austin, Richard E.,Oalmann, Christopher J.,Baker, William R.,Condon, Stephen L.,et al.
, p. 1710 - 1721 (2007/10/02)
The 1,2,3-trisubstituted cyclopropanes 6 and 7 are the first members of a novel class of isosteric replacements for peptide linkages that are more generally represented by the dipeptide mimics 2 and 3.These unique peptide surrogates are specifically desig
