91787-63-2Relevant articles and documents
A Facile Synthesis of 2-Aminopropane-1,2,3-tricarboxylic Acid and Its Symmetrical Dimethyl Ester
Nizovtsev, Alexey V.,Bovin, Nicolai V.
supporting information, p. 4428 - 4432 (2021/08/20)
A new convenient synthetic route to 2-aminopropane-1,2,3-tricarboxylic acid is described. The first two stages of the threestep synthesis are performed in a one-pot procedure and include the cyclization of hippuric acid with DCC followed by treatment with methyl bromoacetate to yield an alkylated oxazolone. Its hydrolysis with HCl provides 2-aminopropane-1,2,3-tricarboxylic acid as its HCl salt. Esterification of the resulting acid with methanol in the presence of thionyl chloride leads selectively to its symmetrical diester.
Synthesis and in vitro carbonic anhydrases and acetylcholinesterase inhibitory activities of novel imidazolinone-based benzenesulfonamides
Tugrak, Mehtap,Gul, Halise Inci,Demir, Yeliz,Levent, Serkan,Gulcin, Ilhami
, (2020/12/09)
New imidazolinone-based benzenesulfonamides 3a–e and 4a–e were synthesized in three steps?and their chemical structures were confirmed by 1H NMR (nuclear magnetic resonance), 13C NMR, and high-resolution mass spectrometry. The benzenesulfonamides used were sulfacetamide (3a, 4a), sulfaguanidine (3b, 4b), sulfanilamide (3c, 4c), sulfadiazine (3d, 4d), sulfamerazine (3e), and sulfathiazole (4e). The compounds were evaluated against carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes to obtain possible drug candidate/s. The lead compounds of the series were 3a and 4a against human CA (hCA) I, whereas?3d and 4a were leads against hCA II in terms of Ki values. Series 4 includes more effective CAs inhibitors than series 3 (except 3d). Series 4 compounds having a nitro group (except 4d) were 3.3–4.8 times more selective inhibitors than their corresponding analogues 3a–d in series 3, in which hydrogen was located in place of the nitro group, by considering Ki values against hCA II. Compounds 3c and 4c, where the sulfanilamide moiety is available, were the leads in terms of AChE inhibition with the lowest Ki values. The use of secondary sulfonamides was a more effective modification on CA inhibition, whereas the primary sulfonamide was the effective substitution in terms of AChE inhibitory potency.
Synthesis and evaluation of new phenyl acrylamide derivatives as potent non-nucleoside anti-HBV agents
Gu, Xiaoke,Zhang, Yinpeng,Zou, Yueting,Li, Xin,Guan, Mingyu,Zhou, Qingqing,Qiu, Jingying
, (2020/12/09)
As a continuation of our previous work, a series of new phenyl acrylamide derivatives (4Aa-g, 4Ba-t, 5 and 6a-c) were designed and synthesized as non-nucleoside anti-HBV agents. Among them, compound 4Bs could potently inhibit HBV DNA replication in wild-type and lamivudine (3TC)/entecavir resistant HBV mutant strains with IC50 values of 0.19 and 0.18 μM, respectively. Notably, the selective index value of 4Bs was above 526, indicating the favorable safety profile. Interestingly, unlike nucleoside analogue 3TC, 4Bs could significantly inhibit 3.5 kb pgRNA expression. Molecular docking study revealed that 4Bs could fit well into the dimer-dimer interface of HBV core protein by hydrophobic, π–π and H-bond interactions. Considering the potent anti-HBV activity, low toxicity and diverse anti-HBV mechanism from that of nucleoside anti-HBV agent 3TC, compound 4Bs might be a promising lead to develop novel non-nucleoside anti-HBV therapeutic agents, and warranted further investigation.
Cu(II)-promoted oxidative C-N bond cleavage of N-benzoylamino acids to primary aryl amides
Zhou, Liandi,Liu, Wei,Zhao, Yongli,Chen, Junmin
, p. 52 - 62 (2021/02/06)
A novel protocol for CuCl2-promoted oxidative C-N bond cleavage of N-benzoyl amino acids was developed. It is the first example of using accessible amino acid as an ammonia synthetic equivalent for the synthesis of primary aryl amides via CuCl2-promoted oxidative C-N bond cleavage reaction. The present protocol shows excellent functional group tolerance and provides an alternative method for the synthetic of primary aryl amides in 84-96% yields.
Design, synthesis and anti-inflammatory/analgesic evaluation of novel di-substituted urea derivatives bearing diaryl-1,2,4-triazole with dual COX-2/sEH inhibitory activities
Abdelazeem, Ahmed H.,El-Din, Asmaa G. Safi,Arab, Hany H.,El-Saadi, Mohammed T.,El-Moghazy, Samir M.,Amin, Noha H.
, (2021/05/19)
Herein, two novel series of diaryl-1,2,4-triazole hybrid to amide conjugates (5a-e) or urea conjugates (10a-f) have been synthesized followed by in vitro evaluation against cyclooxygenase-2/soluble epoxide hydrolase (COX-2/sEH) enzymes using ELISA enzyme assays. In vivo analgesic and anti-inflammatory activities for the new compounds have been carried out using the reported animal protocols. The preliminary results revealed that compounds 10e and 10c were the most active compounds against both COX-2/sEH enzymes (COX-2 IC50 = 1.98 μM and 2.13 μM; sEH = 1.09 and 1.23 nM, respectively). Moreover, the in vivo screening assays confirmed their superiority compared to the other derivatives by exhibiting higher anti-inflammatory and analgesic activity (91.27 and 89.32% edema inhibition; 55.97–50.00% writhing inhibition, respectively) than celecoxib (88.30% edema inhibition; 13.43% writhing inhibition). Collectively, compounds 10e and 10c can be considered as promising dual COX-2/sEH inhibitors with expected less cardiovascular adverse effects affording good anti-inflammatory and analgesic leads for further optimization.
4-Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae
Mancuso, Francesca,De Luca, Laura,Bucolo, Federica,Vrabel, Milan,Angeli, Andrea,Capasso, Clemente,Supuran, Claudiu T.,Gitto, Rosaria
, p. 3787 - 3794 (2021/10/20)
A current issue of antimicrobial therapy is the resistance to treatment with worldwide consequences. Thus, the identification of innovative targets is an intriguing challenge in the drug and development process aimed at newer antimicrobial agents. The state-of-art of anticholera therapy might comprise the reduction of the expression of cholera toxin, which could be reached through the inhibition of carbonic anhydrases expressed in Vibrio cholerae (VchCAα, VchCAβ, and VchCAγ). Therefore, we focused our interest on the exploitation of sulfonamides as VchCA inhibitors. We planned to design and synthesize new benzenesulfonamides based on our knowledge of the VchCA catalytic site. The synthesized compounds were tested thus collecting useful SAR information. From our investigation, we identified new potent VchCA inhibitors, some of them displayed high affinity toward VchCAγ class, for which few inhibitors are currently reported in literature. The best interesting VchCAγ inhibitor (S)-N-(1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)furan-2-carboxamide (40) resulted more active and selective inhibitor when compared with acetazolamide (AAZ) as well as previously reported VchCA inhibitors.
Synthesis, antimicrobial evaluation and docking studies of oxazolone-1,2,3-triazole-amide hybrids
Kumar, Lokesh,Lal, Kashmiri,Kumar, Aman,Kumar, Ashwani
, p. 5079 - 5097 (2021/09/22)
In an attempt to develop quality antimicrobial agents, a series of oxazolone-1,2,3-triazole-amide hybrids were obtained from oxazolone tethered with a terminal alkyne and in situ generated 2-azido-N-phenylacetamides. All the synthesized compounds were characterized by using various spectroscopic techniques. The developed hybrids were evaluated for their in vitro antimicrobial activity toward three Gram-positive bacteria S. aureus, B. subtilis and S. gorodonii and three Gram-negative bacteria—E. coli, S. enterica and P. aeruginosa—and two fungi, viz. C. albicans and A. niger. Oxazolone-amide-1,2,3-triazoles (8a–e, 9a–e, 10a–e) exhibited almost 15 times better efficacy than alkyne precursors, i.e., oxazolone-linked terminal alkynes (6a–c). Compound 10d exhibited very good antimicrobial activity toward all the tested microorganisms. Docking studies of compounds 10d and 6c were also carried out in the binding site of enzyme sterol-14-α-demethylase of C. albicans, which supported the in vitro experimental results.
Site-Specific Oxidation of (sp3)C-C(sp3)/H Bonds by NaNO2/HCl
Zhao, Jianyou,Shen, Tong,Sun, Zhihui,Wang, Nengyong,Yang, Le,Wu, Jintao,You, Huichao,Liu, Zhong-Quan
, p. 4057 - 4061 (2021/05/26)
A site-specific oxidation of (sp3)C-C(sp3) and (sp3)C-H bonds in aryl alkanes by the use of NaNO2/HCl was explored. The method is chemical-oxidant-free, transition-metal-free, uses water as the solvent, and proceeds under mild conditions, making it valuable and attractive to synthetic organic chemistry.
Base Induced Condensation of Malononitrile with Erlenmeyer Azlactones: An Unexpected Synthesis of Multi-Substituted Δ2-Pyrrolines and Their Cytotoxicity
Anil, Seegehalli M.,Kiran, Kuppalli R.,Rajeev, Narasimhamurthy,Sadashiva, Maralinganadoddi P.,Shobith, Rangappa,Sudhanva, Muddenahalli S.,Swaroop, Toreshettahally R.,Vinayaka, Ajjampura C.
, (2020/04/29)
An efficient, metal free approach to synthesize multi-substituted Δ2-pyrroline derivatives by mild base catalyzed cyclocondensation of malononitrile with Erlenmeyer azlactones via 1,2 addition was developed. The modularity of this reaction was used to assemble a range of poly-substituted pyrrolines. Further, synthesized products were screened for cytotoxic properties on different cancer cell lines such as A549 (Human lung adenocarcinoma cells), HeLa (Human cervical adenocarcinoma cells), Jurkat (Human chronic myeloid leukemia cells) and K562 (Human leukemic T cell Lymphoblast cells). Among the synthesized library of compounds, 6f and 6q displayed potent cytotoxic activity.
Synthesis and pharmacological effects of novel benzenesulfonamides carrying benzamide moiety as carbonic anhydrase and acetylcholinesterase inhibitors
Tu?rak, Mehtap,Gül, Halise Inci,Anil, Bar??,Gül?in, Ilhami
, p. 1601 - 1609 (2021/01/05)
N-(1-(4-Methoxyphenyl)-3-oxo-3-((4-(N-(substituted)sulfamoyl)phenyl)amino)prop-1-en-1-yl)benzamides 3a - g were designed since sulfonamide and benzamide pharmacophores draw great attention in novel drug design due to their wide range of bioactivities including acetylcholinesterase (AChE) and human carbonic anhydrase I and II (hCA I and hCA II) inhibitory potencies. Structure elucidation of the compounds was carried out by 1H NMR, 13C NMR, and HRMS spectra. In vitro enzyme assays showed that the compounds had significant inhibitory potential against hCA I, hCA II, and AChE enzymes at nanomolar levels. Ki values were in the range of 4.07 ± 0.38 - 29.70 ± 3.18 nM for hCA I and 10.68 ± 0.98 - 37.16 ± 7.55 nM for hCA II while Ki values for AChE were in the range of 8.91 ± 1.65 - 34.02 ± 5.90 nM. The most potent inhibitors 3g (Ki = 4.07 ± 0.38 nM, hCA I), 3c (Ki = 10.68 ± 0.98 nM, hCA II), and 3f (Ki = 8.91 ± 1.65 nM, AChE) can be considered as lead compounds of this study with their promising bioactivity results. Secondary sulfonamides showed promising enzyme inhibitory effects on AChE while primary sulfonamide derivative was generally effective on hCA I and hCA II isoenzymes.
