Synthesis and analytical characterization of new thiazol-2-(3H)-ones as human neutrophil elastase (HNE) inhibitors; Chemistry Central Journal; Vol. 11
| Parent link: | Chemistry Central Journal Vol. 11.— 2017.— [127, 15 p.] |
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| Korporativna značnica: | |
| Drugi avtorji: | , , , , , , , , , , |
| Izvleček: | Title screen Human neutrophil elastase (HNE) is a potent serine protease belonging to the chymotrypsin family and is involved in a variety of pathologies affecting the respiratory system. Thus, compounds able to inhibit HNE proteolytic activity could represent effective therapeutics. We present here the synthesis of new thiazol-2-(3H)-ones as an elaboration of potent HNE inhibitors with an isoxazol-5-(2H)-one scaffold that we recently identified. Two-dimensional NMR spectroscopic techniques and tandem mass spectrometry allowed us to correctly assign the structure of the final compounds arising from both tautomers of the thiazol-2-(3H)-one nucleus (N-3 of the thiazol-2-(3H)-one and 3-OH of the thiazole). All new compounds were tested as HNE inhibitors, and no activity was found at the highest concentration used (40 [mu]M), demonstrating that the thiazol-2-(3H)-one is not a good scaffold for HNE inhibitors. Molecular modelling experiments indicate that the low-energy pose might limit the nucleophilic attack on the endocyclic carbonyl group of the thiazolone-based compounds by HNE catalytic Ser195, in contrast to isoxazol-5-(2H)-one analogues. Режим доступа: по договору с организацией-держателем ресурса |
| Jezik: | angleščina |
| Izdano: |
2017
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| Teme: | |
| Online dostop: | https://doi.org/10.1186/s13065-017-0358-1 |
| Format: | Elektronski Book Chapter |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=664581 |
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| 200 | 1 | |a Synthesis and analytical characterization of new thiazol-2-(3H)-ones as human neutrophil elastase (HNE) inhibitors |f L. Crocetti, G. Bartolucci, A. Cilibrizzi [et al.] | |
| 203 | |a Text |c electronic | ||
| 300 | |a Title screen | ||
| 320 | |a [References: 30 tit.] | ||
| 330 | |a Human neutrophil elastase (HNE) is a potent serine protease belonging to the chymotrypsin family and is involved in a variety of pathologies affecting the respiratory system. Thus, compounds able to inhibit HNE proteolytic activity could represent effective therapeutics. We present here the synthesis of new thiazol-2-(3H)-ones as an elaboration of potent HNE inhibitors with an isoxazol-5-(2H)-one scaffold that we recently identified. Two-dimensional NMR spectroscopic techniques and tandem mass spectrometry allowed us to correctly assign the structure of the final compounds arising from both tautomers of the thiazol-2-(3H)-one nucleus (N-3 of the thiazol-2-(3H)-one and 3-OH of the thiazole). All new compounds were tested as HNE inhibitors, and no activity was found at the highest concentration used (40 [mu]M), demonstrating that the thiazol-2-(3H)-one is not a good scaffold for HNE inhibitors. Molecular modelling experiments indicate that the low-energy pose might limit the nucleophilic attack on the endocyclic carbonyl group of the thiazolone-based compounds by HNE catalytic Ser195, in contrast to isoxazol-5-(2H)-one analogues. | ||
| 333 | |a Режим доступа: по договору с организацией-держателем ресурса | ||
| 461 | |t Chemistry Central Journal | ||
| 463 | |t Vol. 11 |v [127, 15 p.] |d 2017 | ||
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| 610 | 1 | |a труды учёных ТПУ | |
| 610 | 1 | |a Thiazol-2-(3H)-one | |
| 610 | 1 | |a Synthesis | |
| 610 | 1 | |a LC-MS/MS | |
| 610 | 1 | |a ERMS | |
| 610 | 1 | |a Human neutrophil elastase | |
| 610 | 1 | |a синтез | |
| 610 | 1 | |a нейтрофилы | |
| 610 | 1 | |a ингибиторы | |
| 701 | 1 | |a Crocetti |b L. |g Letizia | |
| 701 | 1 | |a Bartolucci |b G. |g Gianluca | |
| 701 | 1 | |a Cilibrizzi |b A. |g Agostino | |
| 701 | 1 | |a Giovannoni |b M. P. |g Maria Paola | |
| 701 | 1 | |a Guerrini |b G. |g Gabriella | |
| 701 | 1 | |a Iacovone |b A. |g Antonella | |
| 701 | 1 | |a Menicatti |b M. |g Marta | |
| 701 | 1 | |a Shchepyotkin |b I. A. |g Igor Aleksandrovich | |
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