Inhibition of Human Neutrophil Elastase with Peptidyl Electrophilic Ketones. 2. Orally Active PG-Val-Pro-Val Pentafluoroethyl Ketones
| العنوان: | Inhibition of Human Neutrophil Elastase with Peptidyl Electrophilic Ketones. 2. Orally Active PG-Val-Pro-Val Pentafluoroethyl Ketones |
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| المؤلفون: | Michael R. Angelastro, Joseph P. Burkhart, M J Janusz, Chen Tm, Edward W. Huber, Koehl, Baugh Le, S L Durham, Philippe Bey, C M Hare |
| المصدر: | Journal of Medicinal Chemistry. 37:4538-4553 |
| بيانات النشر: | American Chemical Society (ACS), 1994. |
| سنة النشر: | 1994 |
| مصطلحات موضوعية: | Stereochemistry, Molecular Sequence Data, Administration, Oral, Hamster, Hemorrhage, Chemical synthesis, Structure-Activity Relationship, chemistry.chemical_compound, Oral administration, In vivo, Cricetinae, Drug Discovery, Animals, Humans, Amino Acid Sequence, Chromatography, High Pressure Liquid, Dipeptide, Pancreatic Elastase, biology, Elastase, Ketones, Rats, chemistry, Enzyme inhibitor, Lipophilicity, biology.protein, Molecular Medicine, Leukocyte Elastase |
| الوصف: | Valylprolylvalyl pentafluoroethyl ketones with different N-protecting groups were evaluated in vitro and in vivo as inhibitors of human neutrophil elastase (HNE). Several of these compounds were found to be orally active in HNE-induced rat and hamster lung hemorrhage models. The compound with 4-(4-morpholinylcarbonyl)benzoyl as the protecting group, 71 (MDL 101,146), was studied in greater detail. Hydration and epimerization studies were performed on 71 and related compounds in various media, including human blood serum. High-performance liquid chromatography studies on a reversed-phase system as a measure of the lipophilicity of 71 and related compounds revealed a small range of relative retention times wherein the orally active compounds fell. The K i value determined for 71 vs HNE was 25 nM |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c42ac75d902ff0576990760d71e72cc0 https://doi.org/10.1021/jm00052a013 |
| رقم الأكسشن: | edsair.doi.dedup.....c42ac75d902ff0576990760d71e72cc0 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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