15678-99-6Relevant academic research and scientific papers
Templated C-C and C-N Bond Formation Facilitated by a Molybdenum(VI) Metal Center
Zwettler, Niklas,Dupé, Antoine,Schachner, J?rg A.,Belaj, Ferdinand,M?sch-Zanetti, Nadia C.
, p. 11969 - 11976 (2015)
Preparation of molybdenum dioxido complexes with novel iminophenolate ligands bearing pendant secondary amide functionalities led to unprecedented C-C and C-N coupling reactions of two α-iminoamides upon coordination. The diastereoselective cyclization to asymmetric imidazolidines occurs at the metal center in two consecutive steps via a monocoupled intermediate. A meaningful mechanism is proposed on the basis of full characterization of intermediate and final molybdenum-containing products by spectroscopic means and by single-crystal X-ray diffraction analyses. This process constitutes the first example of a diastereoselective self-cyclization of two α-iminoamides.
Neutral and cationic yttrium alkyl complexes with linked 1,4,7-triazacyclononane-amide monoanionic ancillary ligands: Synthesis and catalytic ethene polymerisation
Bambirra,Van Leusen,Meetsma,Hessen,Teuben
, p. 637 - 638 (2001)
Yttrium dialkyl complexes [N,N′-R2-tacn-N″-(CH2)2 NBut]-Y(CH2SiMe3)2 (R = Me, Pri; tacn = 1,4,7-triazacyclononane) were prepared; when activated with [PhNMe2H]-[B(C6F5)4] these complexes form cationic alkyl species that are active ethene polymerisation catalysts.
Synthesis and Structure–Activity Relationship of Thioacetamide-Triazoles against Escherichia coli
Bulitta, Jürgen B.,Dharuman, Suresh,Lee, Richard E.,Reeve, Stephanie M.,Wallace, Miranda J.
supporting information, (2022/03/01)
Infections due to Gram-negative bacteria are increasingly dangerous due to the spread of multi-drug resistant strains, emphasizing the urgent need for new antibiotics with alternative modes of action. We have previously identified a novel class of antibacterial agents, thioacetamide-triazoles, using an antifolate targeted screen and determined their mode of action which is dependent on activation by cysteine synthase A. Herein, we report a detailed examination of the anti-E. coli structure–activity relationship of the thioacetamide-triazoles. Analogs of the initial hit compounds were synthesized to study the contribution of the aryl, thioacetamide, and triazole sections. A clear structure–activity relationship was observed generating compounds with excellent inhibition values. Substitutions to the aryl ring were generally best tolerated, including the introduction of thiazole and pyridine heteroaryl systems. Substitutions to the central thioacetamide linker section were more nuanced; the introduction of a methyl branch to the thioacetamide linker substantially decreased antibacterial activity, but the isomeric propionamide and N-benzamide systems retained activity. Changes to the triazole portion of the molecule dramatically decreased the antibacterial activity, further indicating that 1,2,3-triazole is critical for potency. From these studies, we have identified new lead compounds with desirable in-vitro ADME properties and in-vivo pharmacokinetic properties.
METHODS OF USE FOR PYRIMIDINES AS FERROPORTIN INHIBITORS
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Paragraph 849-852, (2021/11/06)
The subject matter described herein is directed to ferroportin inhibitor compounds of Formula (I) and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of administering the compounds for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis, and also kidney injuries.
Synthesis and Biological Evaluation of 1,2,4-Triazole Thioethers as Both Potential Virulence Factor Inhibitors against Plant Bacterial Diseases and Agricultural Antiviral Agents against Tobacco Mosaic Virus Infections
Fang, Zi-Mian,Guo, Deng-Xuan,Ji, Jin,Liu, Li-Wei,Qi, Pu-Ying,Shao, Wu-Bin,Wang, Jin-Jing,Wang, Pei-Yi,Yang, Song,Zhou, Xiang
, p. 15108 - 15122 (2021/12/27)
Targeting the virulence factors of phytopathogenic bacteria is an innovative strategy for alleviating or eliminating the pathogenicity and rapid outbreak of plant microbial diseases. Therefore, several types of 1,2,4-triazole thioethers bearing an amide l
Design, Synthesis, and SAR Studies of Heteroarylpyrimidines and Heteroaryltriazines as CB2R Ligands
Qian, Hai-Yan,Wang, Zhi-Long,Chen, Li-Li,Pan, You-Lu,Xie, Xiao-Yu,Xie, Xin,Chen, Jian-Zhong
supporting information, p. 2455 - 2463 (2018/11/23)
Herein we describe the design and synthesis of a new series of heteroarylpyrimidine/heteroaryltriazine derivatives on the basis of quinazoline-2,4(1H,3H)-diones as CB2R-selective ligands using a bioisosterism strategy. An acetamide group was explored to displace the enamine linker of the lead compound for the purpose of stereoisomerism elimination and hydrophilicity increase. As a result, some of the synthesized compounds showed high bioactivity and selectivity for CB2R in calcium mobilization assays, and four displayed CB2R agonist activity, with EC50 values below 30 nm. The compound exhibiting the highest agonist activity toward CB2R (EC50=7.53±3.15 nm) had a selectivity over CB1R of more than 1328-fold. Moreover, structure–activity relationship (SAR) studies indicated that the substituents on the nucleus play key roles in the functionality of a ligand, with one such example demonstrating CB2R antagonist activity. Additionally, molecular docking simulations were conducted with the aim of better understanding of these new derivatives in relation to the structural requirements for agonists/antagonists binding to CB2R.
Development of Quinazoline/Pyrimidine-2,4(1H,3H)-diones as Agonists of Cannabinoid Receptor Type 2
Qian, Hai-Yan,Wang, Zhi-Long,Pan, You-Lu,Chen, Li-Li,Xie, Xin,Chen, Jian-Zhong
supporting information, p. 678 - 681 (2017/06/13)
Starting from a prototypical structure 1, we describe our efforts to design and obtain novel quinazoline/pyrimidine-2,4(1H,3H)-diones with high CB2 agonist potency and selectivity as well as improved physicochemical characteristics, mainly hydrophilicity. The most potent and selective CB2 agonists, 8 and 36, in this series were also endowed with lower logP values than that of GW842166X and lead compound 1. These derivatives appear to be promising lead compounds for the development of future CB2 agonists.
Carbamylmethyl Mercaptoacetate Thioether: A Novel Scaffold for the Development of L1 Metallo-β-lactamase Inhibitors
Chang, Ya-Nan,Xiang, Yang,Zhang, Yue-Juan,Wang, Wen-Ming,Chen, Cheng,Oelschlaeger, Peter,Yang, Ke-Wu
supporting information, p. 527 - 532 (2017/05/19)
Given the clinical importance of metallo-β-lactamases (MβLs), a new scaffold, N-substituted carbamylmethyl mercaptoacetate thioether, was constructed. The obtained molecules 1-16 inhibited MβLs from all three subclasses, but preferentially L1 from subclass B3. Compound 9 with a p-carboxyphenyl substituent exhibited the broadest spectrum with at least 70% inhibition of enzymes from all subclasses at 100 μM, while compound 5 with a p-methylphenyl substituent was the most potent inhibitor of any individual enzyme, with 97% inhibition at 100 μM and an IC50 value of 0.41 μM against L1. Isothermal titration calorimetry assays corroborate findings from UV-vis spectrophotometric assays that the inhibition of L1 by 5 is dose-dependent. Docking studies suggest that the carboxyl group, the sulfide atom, and the carbonyl group of the carbamyl coordinate Zn2 in a chelating fashion. Using E. coli cells expressing L1, 6 and 8 were able to decrease cefazolin minimum inhibitory concentration 8-fold.
1,3-dimethyl-7-substituted-quinazolinyl-2,4-diones, and synthesis method and application thereof
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Paragraph 0056; 0057; 0058; 0059; 0060; 0099; 0100, (2017/07/31)
The invention discloses 1,3-dimethyl-7-substituted-quinazolinyl-2,4-diones. The structural general formula of the compounds is disclosed in the specification, wherein R1 is hydrogen or ethyl; and R2 is a benzene ring, benzene ring derivative, heterocyclic ring or aliphatic hydrocarbon. Part of compounds have favorable inhibiting activities for Candida albicans, Aspergillus flavus, Torula histolytica and Aspergillus fumigatus. The compounds have obvious inhibiting activities for chitin synthetase, have favorable antibacterial effects, and can be used for preparing drugs for anti-pathogenic microorganisms.
TREATMENT OF INFECTIOUS DISEASES WITH GLUCOSE UPTAKE INHIBITORS
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Paragraph 0145; 0146, (2017/01/09)
Provided are methods of treating infectious diseases in mammals comprising administering a compound that inhibits glucose uptake. Particular infectious diseases that may be treated include malaria, leishmaniasis, African trypanosomiasis, tuberculosis, HIV, HCMV or herpes virus. In a first aspect, the invention features a method of treating infectious diseases in a mammal, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound or prodrug thereof, or pharmaceutically acceptable salt or ester of said compound or prodrug, wherein the compound is an inhibitor of glucose uptake.
