Academic Journal
A hit expansion of 3‐benzamidopyrazine‐2‐carboxamide: Toward inhibitors of prolyl‐tRNA synthetase with antimycobacterial activity
| العنوان: | A hit expansion of 3‐benzamidopyrazine‐2‐carboxamide: Toward inhibitors of prolyl‐tRNA synthetase with antimycobacterial activity |
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| المؤلفون: | Pallabothula, Vinod Sukanth Kumar, Abdalrahman, Nechirwan Taimur, Mori, Matteo, Fekri, Amir Hossein, Janďourek, Ondřej, Konečná, Klára, Paterová, Pavla, Novák, Martin, Dudášová‐Hatoková, Paulína, Štěrbová‐Kovaříková, Petra, Castellano, Carlo, Meneghetti, Fiorella, Villa, Stefania, Kuneš, Jiří, Juhás, Martin, Zitko, Jan |
| المصدر: | Archiv der Pharmazie ; volume 357, issue 8 ; ISSN 0365-6233 1521-4184 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2024 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | This study presents an exploration of the chemical space around derivatives of 3‐benzamidopyrazine‐2‐carboxamides, previously identified as potent antimycobacterial compounds with predicted binding to mycobacterial prolyl‐transfer RNA synthetase. New urea derivatives (Series‐1) were generally inactive, probably due to their preference for cis ‐ trans conformation (confirmed by density functional theory calculations and experimentally by nuclear overhauser effect spectroscopy NMR). Series‐2 (3‐benzamidopyrazine‐2‐carboxamides with disubstituted benzene ring) demonstrated that substituents larger than fluorine are not tolerated in the ortho position of the benzene ring. This series brought two new compounds ( 21 : R = 2‐F, 4‐Cl and 22 : R = 2‐F, 4‐Br) with in vitro activity against Mycobacterium tuberculosis H37Rv as well as multidrug‐resistant clinical isolates, with minimum inhibitory concentration ranging from 6.25 to 25 μg/mL. The lactone‐type derivatives 4 H ‐pyrazino[2,3‐ d ][1,3]oxazin‐4‐ones (Series‐3) were inactive, but solvent stability studies of compound 29 indicated that they might be developed to usable lactone prodrugs of inhibitors of mycobacterial aspartate decarboxylase (PanD). |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/ardp.202400171 |
| الاتاحة: | http://dx.doi.org/10.1002/ardp.202400171 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ardp.202400171 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.E4DF1E16 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/ardp.202400171 |
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