23776-85-4Relevant articles and documents
Design and Synthesis of 1,2,4-Triazolo[3,2-b]-1,3,5-thiadiazine Derivatives as a Novel Template for Analgesic/Anti-Inflammatory Activity
Sert-Ozgur, Seyma,Tel, Banu C.,Somuncuoglu, Elif I.,Kazkayasi, Inci,Ertan, Mevlut,Tozkoparan, Birsen
, (2017)
Previously, we demonstrated that certain heterocyclic compounds derived from 3-substituted-1,2,4-triazole-5-thiones had promising analgesic/anti-inflammatory activities together with low ulcerogenic properties. Therefore, we sought to design and synthesize new derivatives of triazol-5-thiones-fused heterocycles. In the present study, a series of novel bis-Mannich bases, namely 2,6-disubstituted-6,7-dihydro-5H-1,2,4-triazolo[3,2-b]-1,3,5-thiadiazines (1a–d, 2a–c, and 3a–d), were synthesized and characterized to assess their possible anti-inflammatory/analgesic properties. Additionally, their ability to induce gastric toxicity was also evaluated. Several of the condensed compounds produced a degree of analgesic activity comparable to reference drugs in both the hot plate and tail-flick tests. A strong anti-inflammatory effect was observed for the derivatives carrying a benzyl group at the second position (2a–c). The majority of the prepared compounds caused comparatively less gastrointestinal (GI) side effects than the reference drugs naproxen and indomethacin did. These results showed that 1,2,4-triazolo[3,2-b]-1,3,5-thiadiazine derivatives might afford a safer alternative to currently available analgesic/anti-inflammatory agents for the treatment and management of inflammatory disease and pain.
PCR incorporation of dUMPs modified with aromatic hydrocarbon substituents of different hydrophilicities: Synthesis of C5-modified dUTPs and PCR studies using Taq, Tth, Vent (exo-) and Deep Vent (exo-) polymerases
Chudinov, Alexander V.,Kuznetsova, Viktoriya E.,Miftakhov, Rinat A.,Shershov, Valeriy E.,Surzhikov, Sergey A.,Yurasov, Dmitry A.,Zasedateleva, Olga A.
supporting information, (2020/04/17)
Deoxyuridine triphosphate derivatives (dUTPs) modified at the C5 position of the pyrimidine ring with various aromatic hydrocarbon substituents of different hydrophilicities have been synthesized. The aromatic hydrocarbon substituents were attached to dUTPs via a CH[dbnd]CH[sbnd]CH2[sbnd]NHCO[sbnd]CH2 linker. The efficiency of the PCR incorporation of modified dUMPs using Taq, Tth, Vent (exo-) and Deep Vent (exo-) polymerases and a model DNA template containing one, two and three adjacent adenine nucleotides at three different sites within the sequence was investigated. For all the polymerases used, the yield of the modified PCR product was significantly increased with increasing hydrophilicity of the aromatic hydrocarbon substituent. In particular, for the above polymerases, the efficiency of the incorporation of dUMPs modified with the most hydrophilic of the studied aromatic hydrocarbon substituents, a 4-hydroxyphenyl residue, was 60–85% of the efficiency of dTMP incorporation. At the same time, the relative efficiencies of the incorporation of dUMPs modified with 2-, 4-methoxyphenyl, phenyl and 4-nitrophenyl substituents ranged from 20 to 50% and were 2–18% for the 1-naphthalene and 4-biphenyl groups, which were the most hydrophobic of the studied aromatic hydrocarbon substituents.
Structure-Activity Relationships of Potent, Targeted Covalent Inhibitors That Abolish Both the Transamidation and GTP Binding Activities of Human Tissue Transglutaminase
Akbar, Abdullah,McNeil, Nicole M. R.,Albert, Marie R.,Ta, Viviane,Adhikary, Gautam,Bourgeois, Karine,Eckert, Richard L.,Keillor, Jeffrey W.
, p. 7910 - 7927 (2017/10/06)
Human tissue transglutaminase (hTG2) is a multifunctional enzyme. It is primarily known for its calcium-dependent transamidation activity that leads to formation of an isopeptide bond between glutamine and lysine residues found on the surface of proteins, but it is also a GTP binding protein. Overexpression and unregulated hTG2 activity have been associated with numerous human diseases, including cancer stem cell survival and metastatic phenotype. Herein, we present a series of targeted covalent inhibitors (TCIs) based on our previously reported Cbz-Lys scaffold. From this structure-activity relationship (SAR) study, novel irreversible inhibitors were identified that block the transamidation activity of hTG2 and allosterically abolish its GTP binding ability with a high degree of selectivity and efficiency (kinact/KI > 105 M-1 min-1). One optimized inhibitor (VA4) was also shown to inhibit epidermal cancer stem cell invasion with an EC50 of 3.9 μM, representing a significant improvement over our previously reported "hit" NC9.
