Synthesis of human renin inhibitory peptides, angiotensinogen transition-state analogs containing a Retro-inverso amide bond
| Autor: | Ryoji Yamamoto, Iwao Shimaoka, Nakano Yasushi, Hiromu Harada, Kinji Iizuka, Tetsuhiro Kubota, Hideaki Umeyama, Yoshiaki Kiso, Atsushi Tsubaki, Kenji Akahane, Tetsuhide Kamijo |
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| Rok vydání: | 1990 |
| Předmět: |
Chemistry
Stereochemistry medicine.drug_class Molecular Sequence Data Angiotensinogen Biological activity General Chemistry General Medicine Inhibitory postsynaptic potential Amides Renin inhibitor Structure-Activity Relationship chemistry.chemical_compound Residue (chemistry) Transition state analog Renin Drug Discovery medicine Peptide synthesis Humans Peptide bond Amino Acid Sequence Bioisostere |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 38:3042-3047 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.38.3042 |
| Popis: | The experimental details for the synthesis of human renin inhibitors are described. In order to aviod metabolic degradation of the Phe-His (P3-P2) amide bond in transition-state analogs, structurally modified acyl residues (P4-P3) were incorporated into the inhibitors. Compound 1a, which contained 2-(1-naphthylmethyl)-3-(N-phenethylcarbamoyl)propionyl residue (P4-P3) with a retro-inverso amide bond, L-histidine, and norstatine isoamylamide residue (P1-P1') as a transition-state mimic, had potent human renin inhibitory activity, and it lowered blood pressure when administered orally to common marmosets. |
| Databáze: | OpenAIRE |
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