2-Arylacetamido-4-phenylamino-5-substituted pyridazinones as formyl peptide receptors agonists

التفاصيل البيبلوغرافية
Parent link:Bioorganic & Medicinal Chemistry
Vol. 24, Iss. 11.— 2016.— [P. 2530–2543]
مؤلف مشترك: Национальный исследовательский Томский политехнический университет Институт физики высоких технологий Кафедра биотехнологии и органической химии
مؤلفون آخرون: Vergelli C. Claudia, Schepetkin (Shchepyotkin) I. A. Igor Aleksandrovich, Ciciani G. Giovanna, Cilibrizzi A. Agostino, Crocetti L. Letizia, Giovannoni M. P. Maria Paola, Guerrini G. Gabriella, Iacovone A. Antonella, Kirpotina L. N. Liliya Nikolaevna, Khlebnikov A. I. Andrey Ivanovich, Ye R. D. Richard, Quinn M. T. Mark
الملخص:Title screen
N-Formyl peptide receptors (FPRs: FPR1, FPR2, and FPR3) are G protein-coupled receptors that play key roles in modulating immune cells. FPRs represent potentially important therapeutic targets for the development of drugs that could enhance endogenous anti-inflammation systems associated with various pathologies, thereby reducing the progression of inflammatory conditions. Previously, we identified 2-arylacetamide pyridazin-3(2H)-ones as FPR1- or FPR2-selective agonists, as well as a large number of FPR1/FPR2-dual agonists and several mixed-agonists for the three FPR isoforms. Here, we report a new series of 2-arylacetamido-4-aniline pyridazin-3(2H)-ones substituted in position 5 as a further development of these FPR agonists. Chemical manipulation presented in this work resulted in mixed FPR agonists 8a, 13a and 27b, which had EC50 values in nanomolar range. In particular, compound 8a showed a preference for FPR1 (EC50 = 45 nM), while 13a and 27b showed a moderate preference for FPR2 (EC50 = 35 and 61 nM, respectively). Thus, these compounds may represent valuable tools for studying FPR activation and signaling.
Режим доступа: по договору с организацией-держателем ресурса
منشور في: 2016
الموضوعات:
الوصول للمادة أونلاين:http://dx.doi.org/10.1016/j.bmc.2016.04.019
التنسيق: الكتروني فصل الكتاب
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=649367

MARC

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200 1 |a 2-Arylacetamido-4-phenylamino-5-substituted pyridazinones as formyl peptide receptors agonists  |f C. Vergelli, I. A. Schepetkin (Shchepyotkin), G. Ciciani [et al.] 
203 |a Text  |c electronic 
300 |a Title screen 
320 |a [References: p. 2543 (36 tit.)] 
330 |a N-Formyl peptide receptors (FPRs: FPR1, FPR2, and FPR3) are G protein-coupled receptors that play key roles in modulating immune cells. FPRs represent potentially important therapeutic targets for the development of drugs that could enhance endogenous anti-inflammation systems associated with various pathologies, thereby reducing the progression of inflammatory conditions. Previously, we identified 2-arylacetamide pyridazin-3(2H)-ones as FPR1- or FPR2-selective agonists, as well as a large number of FPR1/FPR2-dual agonists and several mixed-agonists for the three FPR isoforms. Here, we report a new series of 2-arylacetamido-4-aniline pyridazin-3(2H)-ones substituted in position 5 as a further development of these FPR agonists. Chemical manipulation presented in this work resulted in mixed FPR agonists 8a, 13a and 27b, which had EC50 values in nanomolar range. In particular, compound 8a showed a preference for FPR1 (EC50 = 45 nM), while 13a and 27b showed a moderate preference for FPR2 (EC50 = 35 and 61 nM, respectively). Thus, these compounds may represent valuable tools for studying FPR activation and signaling. 
333 |a Режим доступа: по договору с организацией-держателем ресурса 
461 |t Bioorganic & Medicinal Chemistry 
463 |t Vol. 24, Iss. 11  |v [P. 2530–2543]  |d 2016 
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701 1 |a Schepetkin (Shchepyotkin)  |b I. A.  |c doctor-biophysicist  |c leading researcher of Tomsk Polytechnic University, candidate of medical science  |f 1962-  |g Igor Aleksandrovich  |3 (RuTPU)RU\TPU\pers\37358  |9 20276 
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701 1 |a Iacovone  |b A.  |g Antonella 
701 1 |a Kirpotina  |b L. N.  |g Liliya Nikolaevna 
701 1 |a Khlebnikov  |b A. I.  |c Chemist  |c Professor of Tomsk Polytechnic University  |f 1963-  |g Andrey Ivanovich  |3 (RuTPU)RU\TPU\pers\33927  |9 17500 
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