Inhibition of human leukocyte elastase (HLE) by N-substituted peptidyl trifluoromethyl ketones was written by Skiles, Jerry W.;Fuchs, Victor;Miao, Clara;Sorcek, Ronald;Grozinger, Karl G.;Mauldin, Scott C.;Vitous, Jana;Mui, Philip W.;Jacober, Stephen. And the article was included in Journal of Medicinal Chemistry in 1992.Category: esters-buliding-blocks This article mentions the following:
A series of tripeptides possessing trifluoromethyl or aryl kinase residues at P1 were prepared and evaluated both in vitro and in vivo as potential inhibitors of human leukocyte elastase (HLE). Tripeptides containing nonnaturally occurring N-substituted glycine residues at the P2-position have been demonstrated to be potent in vitro inhibitors of HLE, with IC50 values in the submicromolar range. Sterically demanding substituents on the P2-nitrogen have no detrimental effect on in vitro potency. The inhibition process presumably acts via hemiketal formation with the active site Ser195 of HLE, and is facilitated by the strongly electron withdrawing trifluoromethyl functionality. Deletion of the amino acid at the P3-subsite region affords inactive compounds Valine is the preferred residue at the P1-position, whereas the corresponding glycine, alanine, α,α-dimethylglycine, or phenylalanine analogs are all inactive. The compounds described herein all confer a high degree of in vitro specificity when tested against representing cysteine, aspartyl, metallo, and other serine proteases. One of the most potent in vitro inhibitors is tripeptide trifluoromethyl ketone I (IC50 = 0.084 μM). I was also tested in hamsters in an elastase-induced pulmonary hemorrhage (EPH) model. In this model, intratracheal (it) administration of I, 5 min prior to HLE challenge, effectively inhibited hemorrhage in a dose-dependent manner with an ED50 of 4.8 μg. The administration of 20 μg (i.t.) of I 24, 48 and 72 h prior to HLE challenge exhibits significant inhibition against hemorrhage at all time points (97%, 64% and 49%, resp.). In a 21-day chronic model of emphysema in hamsters, 200 μg of HLE administered i.t. caused an elastase-induced emphysema in the lungs which can be quantitated histol. utilizing image anal. In this assay, I significantly inhibited pulmonary lesions associated with septal destruction and increased alveolar spaces, when dosed at 20 μg i.t. 5 min prior to challenge with HLE. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Category: esters-buliding-blocks).
(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Category: esters-buliding-blocks
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Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics