2675-89-0Relevant academic research and scientific papers
Studies in sulfur-nitrogen nucleophilicity
Caserio, Marjorie C.,Kim, Jhong K.
, (2018)
As part of a study of nitrogen vs sulfur nucleophiles, the behavior of methylation products from dimethyl-(2-methylthioethyl)amine CH3SCH2CH2N(CH3)2 1 is described. Of the 2 potential products (a sulf
Design, synthesis, and biological evaluation of 2,6,7-substituted pyrrolo[2,3-d]pyrimidines as cyclin dependent kinase inhibitor in pancreatic cancer cells
Shi, Xingpeng,Quan, Yanni,Wang, Yixuan,Wang, Ying,Li, Yanping
supporting information, (2020/12/29)
Pancreatic cancer is a highly malignant tumor, and more effective treatment is urgently needed to lengthen the life of patients. In this paper a class of new 2,6,7-substituted pyrrolo[2,3-d]pyrimidine derivatives of CDK 4/6 inhibitor ribociclib (1) was de
Palladium-Catalyzed β-C(sp3)-H Arylation of Aliphatic Ketones Enabled by a Transient Directing Group
Wang, Yangyang,Wu, Gaorong,Xu, Xiaobo,Pang, Binghan,Liao, Shaowen,Ji, Yafei
, p. 7296 - 7303 (2021/05/29)
The direct arylation of aliphatic ketones has been developed via Pd-catalyzed β-C(sp3)-H bond functionalization with 2-(aminooxy)-N,N-dimethylacetamide as a novel transient directing group (TDG), which showed remarkable directing ability to generate arylated products in moderate to good yields. Furthermore, the reaction can tolerate abundant substrate of ketones and aryl iodides. This study expands the scope of applications for TDGs.
Novel selective ido1 inhibitors with isoxazolo[5,4-d]pyrimidin-4(5h)-one scaffold
?vajger, Urban,Bratkovi?, Toma?,Dol?ak, Ana,Gobec, Stanislav,Mlinari?, Larisa,Ogorevc, Eva,Sova, Matej
, (2021/04/02)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising target in immunomodulation of several pathological conditions, especially cancers. Here we present the synthesis of a series of IDO1 inhibitors with the novel isoxazolo[5,4-d]pyrimidin-4(5H)-one scaffold. A focused library was prepared using a 6-or 7-step synthetic procedure to allow a systematic investigation of the structure-activity relationships of the described scaffold. Chemistry-driven modifications lead us to the discovery of our best-in-class inhibitors possessing p-trifluoromethyl (23), p-cyclohexyl (32), or p-methoxycarbonyl (20, 39) substituted aniline moieties with IC50 values in the low micromolar range. In addition to hIDO1, compounds were tested for their inhibition of indoleamine 2,3-dioxygenase 2 and tryptophan dioxygenase, and found to be selective for hIDO1. Our results thus demon-strate a successful study on IDO1-selective isoxazolo[5,4-d]pyrimidin-4(5H)-one inhibitors, defining promising chemical probes with a novel scaffold for further development of potent small-molecule immunomodulators.
Quinazoline derivative and application thereof as antitumor drug
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Paragraph 0073-0076, (2020/08/22)
The invention belongs to the technical field of medicinal chemistry, and relates to a quinazoline derivative shown as a general formula (I), physiologically acceptable salt formed by the quinazoline derivative and inorganic or organic acid, a pharmaceutical composition containing the quinazoline derivative and the physiologically acceptable salt, and application of the quinazoline derivative and the pharmaceutical composition to preparation of drugs for treating tumor diseases, particularly drugs for treating abnormal EGFR family diseases. The compound has pharmacological properties with important values, and especially has an inhibition effect on signal transduction caused by tyrosine kinase.
DRUGS TO TREAT OCULAR DISORDERS
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Page/Page column 223, (2019/11/12)
The present invention provides new prodrugs of therapeutically active loop diuretics, including oligomeric prodrugs, and compositions to treat medical disorders, for example, ocular disorders such as glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.
Design and synthesis of aminothiazolyl norfloxacin analogues as potential antimicrobial agents and their biological evaluation
Wang, Liang-Liang,Battini, Narsaiah,Bheemanaboina, Rammohan R.Yadav,Zhang, Shao-Lin,Zhou, Cheng-He
, p. 105 - 123 (2019/02/15)
A series of aminothiazolyl norfloxacin analogues as a new type of potential antimicrobial agents were synthesized and screened for their antimicrobial activities. Most of the prepared compounds exhibited excellent inhibitory efficiencies. Especially, norfloxacin analogue II-c displayed superior antimicrobial activities against K. pneumoniae and C. albicans with MIC values of 0.005 and 0.010 mM to reference drugs, respectively. This compound not only showed broad antimicrobial spectrum, rapid bactericidal efficacy and strong enzymes inhibitory potency including DNA gyrase and chitin synthase (CHS), low toxicity against mammalian cells and no obvious propensity to trigger the development of bacterial resistance, but also exerted efficient membrane permeability, and could effectively intercalate into K. pneumoniae DNA to form a steady supramolecular complex, which might block DNA replication to exhibit their powerful antimicrobial activity. Quantum chemical studies were also performed to explain the high antimicrobial activities. Molecular docking showed that compound II-c could bind with gyrase–DNA and topoisomerase IV–DNA through hydrogen bonds and π-π stacking.
Design and Synthesis of New Aryloxy-linked Dimeric 1,2,3-Triazoles via Click Chemistry Approach: Biological Evaluation and Molecular Docking Study
Deshmukh, Tejshri R.,Khare, Smita P.,Krishna, Vagolu S.,Sriram, Dharmarajan,Sangshetti, Jaiprakash N.,Bhusnure, Omprakash,Khedkar, Vijay M.,Shingate, Bapurao B.
, p. 2144 - 2162 (2019/07/12)
A quest for more potent new antitubercular agents has prompted to design and synthesize aryloxy-linked dimeric 1,2,3-triazoles (4a–j), from azides (2a-e) and bis(prop-2-yn-1-yloxy)benzene (3a–b) on 1,3-dipolar cycloaddition reaction via copper (I)-catalyzed click chemistry approach with good to better yields. The titled compounds (4a–j) were designed using molecular hybridization approach by assembling various bioactive pharmacophoric fragments in a single molecular framework. All the synthesized compounds have been screened for their in vitro antitubercular, antifungal, and antioxidant activities against their respective strains. Among them, 4h and 4i show the highest antifungal activity, whereas compounds 4h, 4i, and 4j have revealed promising antitubercular activity against their respective strains. In addition to this, most of the synthesized compounds were found as potent antifungal and antioxidant agents. A significant network of bonded and non-bonded interactions stabilized these molecules into the active site of fungal CYP51 that is realized from the obtained well-placed docking poses and the associated thermodynamic interactions with the enzyme. The synthesized compounds have also been analyzed for absorption, distribution, metabolism, and excretion properties.
Synthesis, bioevaluation and molecular docking study of new piperazine and amide linked dimeric 1,2,3-triazoles
Deshmukh, Tejshri R.,Khare, Smita P.,Khedkar, Vijay M.,Krishna, Vagolu S.,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.,Sriram, Dharmarajan
supporting information, (2019/12/03)
In search of more potent new antitubercular agents, a library of novel piperazine tethered dimeric 1,2,3-triazoles were designed by assembling 1,2,3-triazoles and piperazine in a single molecular architectural framework. The titled compounds (3a–m) were synthesized by 1,3-dipolar cycloaddition of 1,4-di(prop-2-yn-1-yl)piperazine (1) and various azides (2a–m) using click chemistry approach with good yields. All the synthesized compounds (3a–m) have been screened for their in vitro antitubercular, antifungal and antioxidant activities against their respective strains. Among them, 3b, 3d, and 3i have revealed promising antitubercular activity against Mycobacterium tuberculosis (Mtb) H37Rv with MIC 12.5 μg/mL. Molecular docking results provided well-clustered solutions to the mode of binding for these molecules into the active site of Mtb enoyl reductase (InhA). In addition to this, most of synthesized compounds were found to have potential antifungal as well as antioxidant activity.
Design, synthesis and evaluation of new indolylpyrimidylpiperazines for gastrointestinal cancer therapy
Tan, Aaron,Babak, Maria V.,Venkatesan, Gopalakrishnan,Lim, Clarissa,Klotz, Karl-Norbert,Herr, Deron Raymond,Cheong, Siew Lee,Federico, Stephanie,Spalluto, Giampiero,Ong, Wei-Yi,Chen, Yu Zong,Loo, Jason Siau Ee,Pastori, Giorgia
, (2019/11/02)
Human A3 adenosine receptor hA3AR has been implicated in gastrointestinal cancer, where its cellular expression has been found increased, thus suggesting its potential as a molecular target for novel anticancer compounds. Observation
