- A general procedure for carbon isotope labeling of linear urea derivatives with carbon dioxide
-
Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. This article reports on a general approach to label urea derivatives with all carbon isotopes, including14C and11C, based on a Staudinger aza-Wittig sequence. It provides access to all aliphatic/aromatic urea combinations.
- Babin, Victor,Sallustrau, Antoine,Loreau, Olivier,Caillé, Fabien,Goudet, Amélie,Cahuzac, Hélo?se,Del Vecchio, Antonio,Taran, Frédéric,Audisio, Davide
-
supporting information
p. 6680 - 6683
(2021/07/12)
-
- Synthesis of new derivatives of alepterolic acid via click chemistry
-
Alepterolic acid is a natural diterpenoid isolated from Aleuritopteris argentea (S. G. Gmél.) Fée, a fern with potential medicinal activity, used in China as a folk medicine to regulate menstruation and prevent cancer. Nevertheless, there are few reports
- Aisa, Haji Akber,Cao, Jianguo,Guo, Hongmei,Huang, Guozheng,Jin, Xin,Wang, Qi,Zhao, Qingjie
-
p. 917 - 925
(2021/11/16)
-
- Design and synthesis of novel diosgenin-triazole hybrids targeting inflammation as potential neuroprotective agents
-
Alzheimer's disease is a progressive neurodegenerative disease, and its incidence is expected to increase as the global population ages. Recent studies provide increasing evidence that inflammation plays a key role in the pathogenesis and progression of AD. Diosgenin, an active ingredient in Dioscorea nipponica Makino, is a promising bioactive lead compound in the treatment of Alzheimer's disease, which exhibited anti-inflammatory activity. To search for more efficient anti-Alzheimer agents, a series of novel diosgenin-triazolyl hybrids were designed, synthesized, and their neuroprotective effects against oxygen-glucose deprivation-induced neurotoxicity and LPS-induced NO production were evaluated. Most of these new hybrids displayed better activities than DIO. In particular, the promising compound L6 not only demonstrated an excellent neuroprotective effect but also showed the best anti-inflammatory activity. The structure-activity relationship study illustrated that the introduction of benzyl or phenyl triazole did improve the activity, and the introduction of benzyl triazole was better than that of phenyl triazole. The results we obtained showed that the diosgenin skeleton could be a promising structural template for the development of new anti-Alzheimer drug candidates, and compound L6 has the potential to be an important lead compound for further research.
- Huang, Yi,Huang, Weiwei,Yang, Guixiang,Wang, Rui,Ma, Lei
-
supporting information
(2021/05/21)
-
- NOVEL DIBENZOOXAPHOSPHININE OXIDE DERIVATIVE COMPOUNDS AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DEGENERATIVE DISEASE COMPRISING THE SAME AS AN ACTIVE INGREDIENT
-
The present invention relates to a novel dibenzooxininin oxide derivative compound having various nitrogen-containing substituents introduced at 6-position of a dibenzooxaphosphorin oxide mononuclear, and to the use thereof. The present invention relates to a pharmaceutical composition for preventing or treating degenerative diseases and a health supplement food composition for preventing or treating degenerative diseases, comprising the dibenzooxaphosphorin oxide derivative compound of the present invention.
- -
-
Paragraph 0157-0160
(2021/03/23)
-
- Identification of Phenylphthalazinones as a New Class of Leishmania infantum Inhibitors
-
Leishmaniasis is a neglected parasitic disease caused by over 20 different Leishmania species. Current treatments often rely on harsh regimes of pentavalent antimonials such as sodium stibogluconate, while more recent drugs suffer other shortcomings such
- Sijm, Maarten,de Heuvel, Erik,Matheeussen, An,Caljon, Guy,Maes, Louis,Sterk, Geert-Jan,de Esch, Iwan J. P.,Leurs, Rob
-
supporting information
p. 219 - 227
(2019/12/27)
-
- Sequencing [3+2]-cycloaddition and multicomponent reactions: A regioselective microwave-assisted synthesis of 1,4-disubstituted 1,2,3-triazoles using ionic liquid supported Cu(II) precatalysts in methanol
-
Heterocyclic compounds with two to three nitrogen atoms play a pivotal role in the normal life cycle of a cell. Further the design and synthesis of a quality heterocyclic compound library with N-atoms as new chemical probes active, is vital in drug discov
- Saikia, Ananya Anubhav,Nishanth Rao,Das, Soumyadip,Jena, Sushovan,Rej, Sourav,Maiti, Barnali,Chanda, Kaushik
-
-
- A New Class of Dengue and West Nile Virus Protease Inhibitors with Submicromolar Activity in Reporter Gene DENV-2 Protease and Viral Replication Assays
-
Dengue and West Nile virus are rapidly spreading global pathogens for which no specific therapeutic treatments are available. One of the promising targets for drug discovery against dengue and other flaviviruses is the viral serine protease NS2B-NS3. We present the design, synthesis, and in vitro and cellular characterization of a novel chemotype of potent small-molecule non-peptidic dengue protease inhibitors derived from 4-benzyloxyphenylglycine. A newly developed luciferase-based DENV-2 protease reporter system in HeLa cells (DENV2proHeLa) was employed to determine the activity of the compounds in a cellular environment. Specificity and selectivity of the DENV2proHeLa system were confirmed by viral titer reduction assays. The compounds reach low micromolar to upper nanomolar inhibitory potency in cell-based assays, are selective against other serine proteases, and do not show relevant cytotoxicity. An extensive structure-activity relationship study provides a perspective for further drug development against flaviviral infections.
- Kühl, Nikos,Graf, Dominik,Bock, Josephine,Behnam, Mira A. M.,Leuthold, Mila-Mareen,Klein, Christian D.
-
supporting information
p. 8179 - 8197
(2020/09/21)
-
- Regioselective synthesis of 4-fluoro-1,5-disubstituted-1,2,3-triazoles from synthetic surrogates of α-fluoroalkynes
-
α-Fluoroalkynes are elusive molecules due to their instability and inaccessibility. Here, we show that α-fluoronitroalkenes can serve as synthetic surrogates of α-fluoroalkynes in [3+2] cycloaddition reactions with organic azides facilitated by a catalytic amount of trifluoroacetic acid (TFA). This work provides the first regioselective method to access 4-fluoro-1,5-disubstituted-1,2,3-triazoles.
- Jana, Sampad,Adhikari, Sweta,Cox, Michael R.,Roy, Sudeshna
-
supporting information
p. 1871 - 1874
(2020/02/20)
-
- Design and synthesis of C-ring quinoxaline-substituted sinomenine 1,2,3-triazole derivatives via click reactions
-
The synthesis of C-ring quinoxaline-substituted sinomenine 1,2,3-triazole derivatives at the 4-OH via click reactions is accomplished, and a total of 16 novel sinomenine double N-heterocyclic derivatives are obtained in 74%–95% yields. The C-ring is first transformed into a 1,2-diketone structure under the action of hydrochloric acid, and then reacted with o-phenylenediamine to obtain a C-ring quinoxaline-substituted structure. The 4-OH of sinomenine reacts with chloropropyne to give an alkynyl sinomenine, and then reacts with sodium azide and various benzyl chlorides to give the target compounds. All the synthesized derivatives are characterized by Fourier-transform infrared spectrometry, high resolution mass spectrometry, 1H NMR, and 13C NMR spectroscopy.
- Chen, Xia,Dong, Ling,Gu, Chengwen,Jin, Jie,Lu, Tong,Pan, Hongmei,Tao, Naili,Wang, Ao,Wu, Xuedan,Zhang, Kehua
-
p. 699 - 704
(2020/06/03)
-
- A Nanosized Propeller-like Polyoxometalate-linked Copper(I)-Resorcin[4]arene for Efficient Catalysis
-
The design and assembly of polyoxometalate-resorcin[4]arene-based metal-organic molecular materials are particularly attractive for their elegant structures and potential functions. By applying a newly designed resorcin[4]arene ligand (TPC4R-II), a copper(I)-coordinated polyoxometalate-based metal-organic molecular material, namely, [CuI6(Br)3(TPC4R-II)3(PMo12O40)]·8H2O (1), was rationally assembled. Three copper(I)-coordinated resorcin[4]arenes are held together by a central [PMo12O40]3- to yield a supramolecular propeller. 1 features efficient catalytic performances for oxidation desulfurization (ODS) and azide-alkyne cycloaddition (AAC) reactions. This work affords a feasible method for the nanosized polyoxometalate-based metal-resorcin[4]arene assemblies by well combinating two types of large composites as well as low coordination metal cations.
- Guo, Ting-Ting,Ma, Jian-Fang,Xiong, Yan-Ling,Yang, Jin,Yu, Ming-Yue
-
p. 15402 - 15409
(2020/11/02)
-
- Structure-activity relationship studies and bioactivity evaluation of 1,2,3-triazole containing analogues as a selective sphingosine kinase-2 inhibitors
-
Sphingosine kinase (SphK) is primarily responsible for the production of Sphingosine-1-phosphate (S1P) that plays an important role in many biological and pathobiological processes including cancer, inflammation, neurological and cardiovascular disorders. Most research has focused on developing inhibitors of SphK1 rather than inhibitors of the other isoform SphK2 which has great importance in several pathophysiologic pathways. Exploration of new analogues for improving the potency and selectivity of SphK2 inhibitors is critical. We now have designed, synthesized, and evaluated eighteen new 1,2,3-triazole analogues for their SphK2 inhibitory activity using a ADP-Glo kinase assay, and explored their in vivo anti-tumor bioactivity. Several compounds including 21c, 21e, 21g, 25e-h, 29a-c have high selectivity for SphK2 over SphK1; compound 21g displayed the highest potency with an IC50 value of 0.23 μM. In addition, three compounds 21a, 21b, and 25b have high anti-tumor activity against U-251 MG human glioblastoma cells. Molecular modeling study was performed to elucidate the polar head group and 1,2,3-triazole pharmacophore impact on the SphK2 selectivity.
- Graham, Thomas J. A.,Gropler, Robert,Jiang, Hao,Liu, Hui,Perlmutter, Joel,Rogers, Buck E.,Tangadanchu, Vijai Kumar Reddy,Tu, Zhude,Yu, Yanbo
-
-
- NOVEL TETRAZOLE COMPOUNDS AND THEIR USE IN THE TREATMENT OF TUBERCULOSIS
-
The invention relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by mycobacterium, such as tuberculosis.
- -
-
Page/Page column 61; 62
(2019/03/05)
-
- Tuning Molecular Vibrational Energy Flow within an Aromatic Scaffold via Anharmonic Coupling
-
From guiding chemical reactivity in synthesis or protein folding to the design of energy diodes, intramolecular vibrational energy redistribution harnesses the power to influence the underlying fundamental principles of chemistry. To evaluate the ability
- Schmitz, Andrew J.,Pandey, Hari Datt,Chalyavi, Farzaneh,Shi, Tianjiao,Fenlon, Edward E.,Brewer, Scott H.,Leitner, David M.,Tucker, Matthew J.
-
p. 10571 - 10581
(2019/12/24)
-
- Design, synthesis, in-vitro evaluation and molecular docking studies of novel indole derivatives as inhibitors of SIRT1 and SIRT2
-
Sirtuins (SIRTs), class III HDAC (Histone deacetylase) family proteins, are associated with cancer, diabetes, and other age-related disorders. SIRT1 and SIRT2 are established therapeutic drug targets by regulating its function either by activators or inhi
- Manjula, Ramu,Gokhale, Nikhila,Unni, Sruthi,Deshmukh, Prashant,Reddyrajula, Rajkumar,Srinivas Bharath,Dalimba, Udayakumar,Padmanabhan, Balasundaram
-
-
- Identification of highly potent and selective Cdc25 protein phosphatases inhibitors from miniaturization click-chemistry-based combinatorial libraries
-
Cell division cycle 25 (Cdc25) protein phosphatases play key roles in the transition between the cell cycle phases and their association with various cancers has been widely proven, which makes them ideal targets for anti-cancer treatment. Though several Cdc25 inhibitors have been developed, most of them displayed low activity and poor subtype selectivity. Therefore, it is extremely important to discover novel small molecule inhibitors with potent activities and significant selectivity for Cdc25 subtypes, not only served as drugs to treat cancer but also to probe its mechanism in transitions. In this study, miniaturized parallel click chemistry synthesis via CuAAC reaction followed by in situ biological screening were used to discover selective Cdc25 inhibitors. The bioassay results showed that compound M2N12 proved to be the most potent Cdc25 inhibitor, which also act as a highly selective Cdc25C inhibitor and was about 9-fold potent than that of NSC 663284. Moreover, M2N12 showed remarkable anti-growth activity against the KB-VIN cell line, equivalent to that of PXL and NSC 663284. An all-atom molecular dynamics (MD) simulation approach was further employed to probe the significant selectivity of M2N12 for Cdc25C relative to its structural homologs Cdc25A and Cdc25B. Overall, above results make M2N12 a promising lead compound for further investigation and structural modification.
- Jing, Lanlan,Wu, Gaochan,Hao, Xia,Olotu, Fisayo A.,Kang, Dongwei,Chen, Chin Ho,Lee, Kuo-Hsiung,Soliman, Mahmoud E.S.,Liu, Xinyong,Song, Yuning,Zhan, Peng
-
-
- Polyoxometalate-Bridged Cu(I)- And Ag(I)-Thiacalix[4]arene Dimers for Heterogeneous Catalytic Oxidative Desulfurization and Azide-Alkyne "click" Reaction
-
Two remarkable polyoxometalate-bridged Cu(I)- and Ag(I)-thiacalix[4]arene dimers, namely, [Cu4(SiW12O40)(L)2(DMF)2]·2EtOH·DMF (1-Cu) and [Ag4(PMo12O40)(L)2]·OH (1-Ag), were prepared by using a new thiacalix[4]arene, metal cation and polyoxometalate (L = tetra[2-(ethylthio)-1-methyl-1H-imidazole]-thiacalix[4]arene). In 1-Cu and 1-Ag, two thiacalix[4]arenes were linked together by one [SiW12O40]4- or [PMo12O40]3- anion via two metal cations to give a molecular dimer. Further, adjacent dimers were extended into a high-dimensional supramolecular architecture through hydrogen bonds. Markedly, these molecular dimers are exceedingly stable in organic solvents and then were employed as efficient catalysts for catalytic oxidation desulfurization as well as the azide-alkyne "click" reaction.
- Yu, Ming-Yue,Guo, Ting-Ting,Shi, Xiao-Chuan,Yang, Jin,Xu, Xianxiu,Ma, Jian-Fang,Yu, Zhen-Tao
-
supporting information
p. 11010 - 11019
(2019/08/26)
-
- Carcarinic acid-1, 2, 3- based triazole compound as well as preparation method and application thereof (by machine translation)
-
The method comprises the following steps: firstly 1, 2, 3 - oxidizing and opening the carbon- carbon double bond of the, carcarinic acid into methylene to, obtain carcarinic acid (not shown, in the technical field of, organic 3 - synthesis), Wolf - Kishner - 1, 2, 3 - 1, 2, 3 - 1, 2, 3 - 3 . (by machine translation)
- -
-
Paragraph 0190-0192
(2019/12/25)
-
- Hit discovery of Mycobacterium tuberculosis inosine 5′-monophosphate dehydrogenase, GuaB2, inhibitors
-
Tuberculosis remains a global concern. There is an urgent need of newer antitubercular drugs due to the development of resistant forms of Mycobacterium tuberculosis (Mtb). Inosine 5′-monophosphate dehydrogenase (IMPDH), guaB2, of Mtb, required for guanine nucleotide biosynthesis, is an attractive target for drug development. In this study, we screened a focused library of 73 drug-like molecules with desirable calculated/predicted physicochemical properties, for growth inhibitory activity against drug-sensitive MtbH37Rv. The eight hits and mycophenolic acid, a prototype IMPDH inhibitor, were further evaluated for activity on purified Mtb-GuaB2 enzyme, target selectivity using a conditional knockdown mutant of guaB2 in Mtb, followed by cross-resistance to IMPDH inhibitor-resistant SRMV2.6 strain of Mtb, and activity on human IMPDH2 isoform. One of the hits, 13, a 5-amidophthalide derivative, has shown growth inhibitory potential and target specificity against the Mtb-GuaB2 enzyme. The hit, 13, is a promising molecule with potential for further development as an antitubercular agent.
- Sahu, Niteshkumar U.,Singh, Vinayak,Ferraris, Davide M.,Rizzi, Menico,Kharkar, Prashant S.
-
p. 1714 - 1718
(2018/05/05)
-
- Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library
-
The HIV-1 capsid (CA) protein plays essential roles in both early and late stages of HIV-1 replication and is considered an important, clinically unexploited therapeutic target. As such, small drug-like molecules that inhibit this critical HIV-1 protein h
- Wu, Gaochan,Zalloum, Waleed A.,Meuser, Megan E.,Jing, Lanlan,Kang, Dongwei,Chen, Chin-Ho,Tian, Ye,Zhang, Fangfang,Cocklin, Simon,Lee, Kuo-Hsiung,Liu, Xinyong,Zhan, Peng
-
p. 478 - 492
(2018/09/25)
-
- Design of a DNA-Programmed Plasminogen Activator
-
Although the functional specificity and catalytic versatility of enzymes have been exploited in numerous settings, controlling the spatial and temporal activity of enzymes remains challenging. Here we describe an approach for programming the function of s
- Mukherjee, Purba,Leman, Luke J.,Griffin, John H.,Ghadiri, M. Reza
-
p. 15516 - 15524
(2018/11/30)
-
- Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry
-
The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50 = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10 μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100 μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.
- Cao, Jiangying,Ma, Chunhua,Zang, Jie,Gao, Shuai,Gao, Qianwen,Kong, Xiujie,Yan, Yugang,Liang, Xuewu,Ding, Qin'ge,Zhao, Chunlong,Wang, Binghe,Xu, Wenfang,Zhang, Yingjie
-
p. 3145 - 3157
(2018/06/01)
-
- Development of new scaffolds as reversible tissue transglutaminase inhibitors, with improved potency or resistance to glutathione addition
-
Previous studies within our group have yielded a class of cinnamoyl-based competitive reversible inhibitors for tissue transglutaminase (TG2), with Ki values as low as 1.0 μM (compound CP4d). However, due to the electrophilic nature of their al
- Apperley, Kim Y. P.,Roy, Isabelle,Saucier, Vincent,Brunet-Filion, Nicholas,Piscopo, Sara-Pier,Pardin, Christophe,De Francesco, élise,Hao, Catherine,Keillor, Jeffrey W.
-
supporting information
p. 338 - 345
(2017/03/08)
-
- Benzylic C-H Azidation Using the Zhdankin Reagent and a Copper Photoredox Catalyst
-
An azidation method for C-N bond formation at benzylic C-H positions is described using copper-catalyzed visible light photochemistry and the Zhdankin azidoiodinane reagent. The method is applicable to a wide range of substrates bearing different functional groups and having a primary, secondary, or tertiary benzylic position, and is thought to proceed through a radical chain reaction.
- Rabet, Pauline T. G.,Fumagalli, Gabriele,Boyd, Scott,Greaney, Michael F.
-
supporting information
p. 1646 - 1649
(2016/04/26)
-
- Synthesis of novel 5-[(1,2,3-triazol-4-yl)methyl]-1-methyl-3H-pyridazino[4,5-b]indol-4-one derivatives by click reaction and exploration of their anticancer activity
-
A series of pyridazino[4,5-b]indole derivatives containing alkyl-, benzyl- and phenacyl-substituted 1,2,3-triazolylmethyl units was synthesized using click chemistry approach. All 30 compounds of the series were screened in vitro against four cancer cell lines, viz. breast cancer cells MDA-MB-231 and MCF 7, human primary glioblastoma U-87 and human neuroblastoma IMR-32 cell lines. Most of the compounds exhibited potent cancer cell growth inhibition activity at very low micromolar concentrations. The IC50 value of compounds 7v and 7x against human neuroblastoma IMR-32 cell line is 0.07 and 0.04 μM, respectively. Among the tested compounds, ten compounds showed IC50 value less than 1 μM against MDA-MB-231 cells, whereas against IMR-32 cells, nine compounds and, against U-87 cells, six compounds showed similar inhibition activity. Further, these molecules exhibited prominent binding affinity and docking scores in the molecular simulation study with the target enzyme PI3 kinase. Graphical Abstract: This paper illustrates the synthesis of new fused indole-pyridazinone derivatives containing substituted 1,2,3-triazoles via click chemistry approach. Most of the compounds exhibited potent cancer cell growth inhibition activity at very low micromolar concentrations. [Figure not available: see fulltext.]
- Panathur, Naveen,Gokhale, Nikhila,Dalimba, Udayakumar,Koushik, Pulla Venkat,Yogeeswari, Perumal,Sriram, Dharmarajan
-
p. 135 - 148
(2016/01/25)
-
- From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)
-
The sphingosine kinase (SK) inhibitor, SKI-II, has been employed extensively in biological investigations of the role of SK1 and SK2 in disease and has demonstrated impressive anticancer activity in vitro and in vivo. However, interpretations of results u
- Aurelio, Luigi,Scullino, Carmen V.,Pitman, Melissa R.,Sexton, Anna,Oliver, Victoria,Davies, Lorena,Rebello, Richard J.,Furic, Luc,Creek, Darren J.,Pitson, Stuart M.,Flynn, Bernard L.
-
p. 965 - 984
(2016/02/23)
-
- O-(triazolyl)methyl carbamates as a novel and potent class of Fatty Acid Amide Hydrolase (FAAH) inhibitors
-
Inhibition of fatty acid amide hydrolase (FAAH) activity is under investigation as a valuable strategy for the treatment of several disorders, including pain and drug addiction. A number of potent FAAH inhibitors belonging to different chemical classes have been disclosed to date; O-aryl carbamates are one of the most representative families. In the search for novel FAAH inhibitors, a series of O-(1,2,3-triazol-4-yl)methyl carbamate derivatives were designed and synthesized exploiting a coppercatalyzed [3+2] cycloaddition reaction between azides and alkynes (click chemistry). Exploration of the structure-activity relationships within this new class of compounds identified potent inhibitors of both rat and human FAAH with IC50 values in the single-digit nanomolar range. In addition, these derivatives showed improved stability in rat plasma and kinetic solubility in buffer with respect to the lead compound. Based on the results of the study, the novel analogues identified can be considered to be promising starting point for the development of new FAAH inhibitors with improved drug-like properties.
- Colombano, Giampiero,Albani, Clara,Ottonello, Giuliana,Ribeiro, Alison,Scarpelli, Rita,Tarozzo, Glauco,Daglian, Jennifer,Jung, Kwang-Mook,Piomelli, Daniele,Bandiera, Tiziano
-
supporting information
p. 380 - 395
(2015/02/05)
-
- One-pot sequential alkynylation and cycloaddition: Regioselective construction and biological evaluation of novel benzoxazole-triazole derivatives
-
Individually, benzoxazole and triazole moieties are of significant biological interest owing to their importance in drugs and pharmaceuticals. To assess their combined biological impact when woven into one molecule, we designed a novel, regioselective, multicomponent, one-pot (MCOP) approach for the construction of benzoxazole-linked triazoles. The synthesis has been achieved in two sequential steps involving copper-catalyzed alkynylation of benzoxazole followed by a 1,3-dipolar cycloaddition reaction. By combination of these two bioactive units into one core, a series of new benzoxazole-triazole scaffolds has been synthesized and subjected to in vitro antibacterial and anticancer evaluation. Tests against clinical isolates of Staphylococcus aureus and Escherichia coli showed potent Gram-negative activity for compounds 4{1,1,1}, 4{1,1,4}, and 4{1,2,1}. The cytotoxicity of the synthesized library was determined against three cancer cell lines: HeLa, SKBr3, and Hep G2. Compound 4{2,2,2} showed significant cytotoxicity against all the cell lines. These preliminary bioassay evaluations strongly suggest the promise and scope of these novel molecules as therapeutic agents in medical science.
- Srivastava, Ananya,Aggarwal, Leena,Jain, Nidhi
-
-
- New indole-isoxazolone derivatives: Synthesis, characterisation and in vitro SIRT1 inhibition studies
-
A new series of indole-isoxazolone hybrids bearing substituted amide, substituted [(1,2,3-triazol-4-yl)methoxy]methyl group or substituted benzylic ether at position-2 of the indole nucleus was synthesised using a facile synthetic route and the molecules
- Panathur, Naveen,Gokhale, Nikhila,Dalimba, Udayakumar,Koushik, Pulla Venkat,Yogeeswari, Perumal,Sriram, Dharmarajan
-
supporting information
p. 2768 - 2772
(2015/06/08)
-
- 'Click' ligand for 'click' chemistry: (1-(4-methoxybenzyl)-1-H-1,2,3-triazol-4-yl)methanol (MBHTM) accelerated copper-catalyzed [3+2] azide-alkyne cycloaddition (CuAAC) at low catalyst loading
-
Readily accessible, cost effective, remarkably stable and easily tunable 1,2,3-triazole based ligand, (1-(4-methoxybenzyl)-1-H-1,2,3-triazol-4-yl)methanol (MBHTM) synthesized itself by 'click' chemistry shown to promote the dramatic rate enhancement of co
- Tale, Rajesh H.,Gopula, Venkatesh B.,Toradmal, Gopal K.
-
supporting information
p. 5864 - 5869
(2015/11/02)
-
- Synthesis and antifungal activity of benzamidine derivatives carrying 1,2,3-triazole moieties
-
Eighteen novel benzamidine derivatives containing 1,2,3-triazole moieties were synthesized. The in vitro and in vivo fungicidal acitivities of the title compounds and the arylamidine intermediates against Colletotrichum lagenarium and Botrytis cinerea wer
- Chen, Guangyou,Zhou, Yiwan,Cai, Chonglin,Lu, Jia,Zhang, Xing
-
p. 5674 - 5691
(2014/06/10)
-
- Biological evaluation of new mimetics of annonaceous acetogenins: Alteration of right scaffold by click linkage with aromatic functionalities
-
A small library of analogues of annonaceous acetogenins through click linkage with aromatic moieties is established using a convergent modular fragment-assembly approach. These analogues exhibited low micromolar inhibitory activities against the proliferation of several human cancer cell lines. Structure-activity relationship (SAR) of these analogues indicates that replacement of the methoxy groups of ubiquinone ring with methyl groups is proved to be a useful strategy for improving the anticancer activity of quinone-acetogenin hybrids.
- Liu, Yanghan,Xiao, Qicai,Liu, Yongqiang,Li, Zheng,Qiu, Yatao,Zhou, Guang-Biao,Yao, Zhu-Jun,Jiang, Sheng
-
p. 248 - 258
(2014/04/17)
-
- A green and efficient access to aryl nitriles via an electrochemical anodic oxidation
-
The nitrile functionality is a key building block in synthetic chemistry, and has wide applications in pharmaceuticals. However, traditional methodologies for the synthesis of nitriles are limited to harsh reaction conditions. Herein, we report a new and efficient access to aryl nitriles by an electrochemical synthesis. Compared with the conventional synthetic methods, this electrochemical synthesis is more environmentally friendly and easier to handle.
- Ye, Jia-Qian,Zhang, Zhen-Lei,Zha, Zheng-Gen,Wang, Zhi-Yong
-
supporting information
p. 1112 - 1114
(2014/08/18)
-
- Trapping of azidocarbenium ion: A unique route for azide synthesis
-
For the first time, a sensitive azidocarbenium ion intermediate has been trapped with various nucleophiles to provide azides in excellent chemoselectivity. This provides a novel approach for the chemoselective synthesis of primary and secondary benzyl azides from aldehydes in a one-pot reaction. Enantioselective nucleophilic addition to the azidocarbenium ion has also been initiated.
- Pramanik, Suman,Ghorai, Prasanta
-
supporting information
p. 2104 - 2107
(2014/05/06)
-
- SPIROHYDANTOIN COMPOUNDS AND THEIR USE AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
-
The present invention relates to a compound of formula (1-1 ) in free form or in pharmaceutically acceptable salt form in which the substituents are as defined in the specification; to its preparation, to its use as a medicament and to medicaments comprising it. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
- -
-
Page/Page column 65
(2013/09/12)
-
- Synthesis and antifungal activity of the novel triazole derivatives containing 1,2,3-triazole fragment
-
A series of fluconazole analogues containing 1,2,3-triazole fragment have been designed and synthesized on the basis of the active site of the cytochrome P450 14α-demethylase (CYP51). Their structures were characterized by 1H NMR, 13C NMR and LC-MS. The MIC80 values indicate that the target compounds 1a-r showed higher activities against nearly all the fungi tested to some extent except against Aspergillus fumigatus. Compounds 1c, e, f, l and p showed 128 times higher activity (with the MIC 80 value of 0.0039 mg/mL) than that of fluconazole against Candida albicans and also showed higher activity than that of the other positive controls.
- Yu, Shichong,Wang, Nan,Chai, Xiaoyun,Wang, Baogang,Cui, Hong,Zhao, Qingjie,Zou, Yan,Sun, Qingyan,Meng, Qingguo,Wu, Qiuye
-
p. 1215 - 1222
(2013/11/06)
-
- Facile synthesis of 1,2,3-triazole analogs of SGLT2 inhibitors by 'click chemistry'
-
Novel analogs of SGLT2 inhibitors containing the 1,2,3-triazole motif were designed and synthesized for urinary glucose excretion evaluation. The C-glucosides with triazole aglycone can be easily constructed by click chemistry. Most of the synthesized compounds increased urinary glucose excretion and demonstrated inhibition of glucose transport.
- Li, Lan-Tao,Zhou, Li-Fei,Li, Yan-Jun,Huang, Juan,Liu, Rui-Hua,Wang, Bin,Wang, Peng
-
supporting information; experimental part
p. 642 - 644
(2012/03/11)
-
- Synthesis and antimalarial activities of a diverse set of triazole-containing furamidine analogues
-
Four different series of triazole diamidines have been prepared by the Pinner method from the corresponding triazole dinitriles. Copper-catalyzed "click chemistry" was used for the synthesis of 1,4- and 4,5-substituted triazoles, aryl magnesium acetylide
- Berger, Olivier,Kaniti, Archana,van Ba, Christophe Tran,Vial, Henri,Ward, Stephen A.,Biagini, Giancarlo A.,Bray, Patrick G.,O'Neill, Paul M.
-
experimental part
p. 2094 - 2108
(2012/06/18)
-
- A copper(I) isonitrile complex as a heterogeneous catalyst for azide-alkyne cycloaddition in water
-
A structurally well-defined copper(I) isonitrile complex is shown to be an efficient, heterogeneous catalyst for the Huisgen azide-alkyne 1,3-dipolar cycloaddition under mild conditions in water. Notably, this catalyst can also be utilized in a three-component reaction of halides, sodium azide and alkynes to form 1,4-disubstituted 1,2,3-triazoles in high yields. Furthermore, it can be readily recovered by precipitation and filtration and recycled for at least five runs without significant loss of activity.(Figure Presented)
- Liu, Meina,Reiser, Oliver
-
supporting information; experimental part
p. 1102 - 1105
(2011/04/24)
-
- Synthesis and structure-activity relationship of 1- and 2-substituted-1,2,3-triazole letrozole-based analogues as aromatase inhibitors
-
A series of bis- and mono-benzonitrile or phenyl analogues of letrozole 1, bearing (1,2,3 and 1,2,5)-triazole or imidazole, were synthesized and screened for their anti-aromatase activities. The unsubstituted 1,2,3-triazole 10a derivative displayed inhibitory activity comparable with that of the aromatase inhibitor, letrozole 1. Compound 10a, bearing a 1,2,3-triazole, is also 10000-times more tightly binding than the corresponding analogue 25 bearing a 1,2,5-triazole, which confirms the importance of a nitrogen atom at position 3 or 4 of the 5-membered ring needed for high activity. The effect on human epithelial adrenocortical carcinoma cell line (H295R) proliferation was also evaluated. The compound 10j (IC50 = 4.64 μM), a letrozole 1 analogue bearing para-cyanophenoxymethylene-1,2,3-triazole decreased proliferation rates of H295R cells by 76 and 99% in 24 and 72 h respectively. Computer calculations, using quantum ab initio structures, suggest a possible correlation between anti-aromatase activity and the distance between the nitrogen in position 3 or 4 of triazole nitrogen and the cyano group nitrogen.
- Doiron, Jeremie,Soultan, Al Haliffa,Richard, Ryan,Toure, Mamadou Mansour,Picot, Nadia,Richard, Remi,Cuperlovic-Culf, Miroslava,Robichaud, Gilles A.,Touaibia, Mohamed
-
scheme or table
p. 4010 - 4024
(2011/10/30)
-
- Microwave-assisted benzyne-click chemistry: preparation of 1H-benzo[d][1,2,3]triazoles
-
The benzotriazoles were prepared by three-component and two-component microwave-assisted [3+2] cycloadditions of various azides to benzyne, 3-methoxybenzyne, and 4,5-difluorobenzyne. In the three-component reaction, the aryne is generated, in the presence of an azide prepared in situ, by the reaction of an o-(trimethylsilylaryl) triflate with either CsF or KF/18-Crown-6. However, in the two-component reactions, a freshly prepared azide is added to the reaction vessel prior to aryne generation. Good to excellent yields of benzotriazoles were obtained in 15-20 min when the microwave-assisted reactions were carried out at 125 °C. These reaction times are significantly faster than similar reactions carried out using conventional heating.
- Ankati, Haribabu,Biehl, Ed
-
supporting information; experimental part
p. 4677 - 4682
(2009/10/26)
-
- [(NHC)2Cu]X complexes as efficient catalysts for azide-alkyne click chemistry at low catalyst loadings
-
(Chemical Equation Presented) La click, c'est chic! A catalytic system based on an [(NHC)2Cu]X complex (NHC=N-heterocyclic carbene) was developed for the [3+2] cycloaddition of azides with alkynes under click conditions (see scheme). This syste
- Diez-Gonzlez, Silvia,Nolan, Steven P.
-
supporting information; experimental part
p. 8881 - 8884
(2009/05/26)
-
- A [(NHC)CuCl] complex as a latent Click catalyst
-
A latent catalyst for the [3+2] cycloaddition reaction of azides and alkynes has been developed in accordance with the principles of Click chemistry. The Royal Society of Chemistry.
- Diez-Gonzalez, Silvia,Stevens, Edwin D.,Nolan, Steven P.
-
supporting information; experimental part
p. 4747 - 4749
(2009/03/12)
-
- (NHC)copper(I)-catalyzed [3+2] cycloaddition of azides and Mono- Or disubstituted alkynes
-
A versatile and highly efficient catalyst for the Huisgen cycloaddition reaction has been developed. Previously isolated or in situ generated azides yielded 1,2,3-triazoles with differently substituted alkynes in the presence of a [(NHC)CuBr] complex (NHC
- Diez-Gonzalez, Silvia,Correa, Andrea,Cavallo, Luigi,Nolan, Steven P.
-
p. 7558 - 7564
(2007/10/03)
-
- 4-HYDROXYQUINOLINE-3-CARBOXAMIDES AND HYDRAZIDES AS ANTIVIRAL AGENTS
-
The present invention provides 4-hydroxyquinoline-3-carboxamide and hydrazide compounds of formula I These compounds are useful to treat or prevent the herpesviral infections, particularly, human cytomegaloviral infection.
- -
-
Page/Page column 124
(2010/02/13)
-
- Preparation of a clinically investigated ras farnesyl transferase inhibitor
-
The synthesis of ras farnesyl-protein transferase inhibitor 1 is described on a multi-kilogram scale. Retrosynthetic analysis reveals chloromethylimidazole 2 and a piperazinone 3 as viable precursors. The 1,5-disubstituted imidazole system was regioselectively assembled via an improved Marckwald imidazole synthesis. A new imidazole dethionation procedure has been developed to convert the Marckwald mercaptoimidazole product to the desired imidazole. This methodology was found to be tolerant of a variety of functional groups providing good to excellent yields of 1,5-disubstituted imidazoles. A new Mitsunobu cyclization strategy was developed to prepare the arylpiperazinone fragment 3.
- Maligres, Peter E.,Waters, Marjorie S.,Weissman, Steven A.,McWilliams, J. Christopher,Lewis, Stephanie,Cowen, Jennifer,Reamer, Robert A.,Volante,Reider, Paul J.,Askin, David
-
p. 229 - 241
(2007/10/03)
-
- Thrombin inhibitors having a lactam at P3
-
The present invention provides compounds having a lactam ring at P3 and at P1 have a six-membered heterocyclic ring having two ring nitrogen ring atoms and the remainder of the ring atoms carbon atoms. These compounds have biological activity as active and potent inhibitors of thrombin. Their pharmaceutically acceptable salts, pharmaceutical compositions thereof and methods of using these compounds and pharmaceutical compositions comprising these compounds as therapeutic agents for treatment of disease states in mammals which are characterized by abnormal thrombosis are also described.
- -
-
-
- Non-covalent inhibitors of urokinase and blood vessel formation
-
Novel compounds having activity as non-covalent inhibitors of urokinase and having activity in reducing or inhibiting blood vessel formation are provided. These compounds have P1 a group having an amidino or guanidino moiety or derivative thereof. These compounds are useful in vitro for monitoring plasminogen activator levels and in vivo in treatment of conditions which are ameliorated by inhibition of or decreased activity of urokinase and in treating pathologic conditions wherein blood vessel formation is related to a pathologic condition.
- -
-
-
- Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position
-
Thrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the α-thrombin-hirugen complex provides an explanation for these unanticipated results.
- Rittle, Kenneth E.,Barrow, James C.,Cutrona, Kellie J.,Glass, Kristen L.,Krueger, Julie A.,Kuo, Lawrence C.,Lewis, S. Dale,Lucas, Bobby J.,McMasters, Daniel R.,Morrissette, Matthew M.,Nantermet, Philippe G.,Newton, Christina L.,Sanders, William M.,Yan, Youwei,Vacca, Joseph P.,Selnick, Harold G.
-
p. 3477 - 3482
(2007/10/03)
-
- Novel, potent non-covalent thrombin inhibitors incorporating P3-lactam scaffolds
-
Evolution of P1-argininal inhibitor prototypes led to a series of non-covalent P3-7-membered lactam inhibitors 1a-w, featuring novel peptidomimetic units that probe each of the S1, S2, and S3 specificity pockets of thrombin. Rigid P1-arginine surrogates possessing a wide range of basicity (calcd pKa's~neutral-14) were surveyed. The design, synthesis, and biological activity of these targets are presented.
- Ho, Jonathan Z.,Gibson, Tony S.,Semple
-
p. 743 - 748
(2007/10/03)
-
- Non-covalent inhibitors of urokinase and blood vessel formation
-
Novel compounds having activity as non-covalent inhibitors of urokinase and having activity in reducing or inhibiting blood vessel formation are provided. These compounds have Pi a group having an amidino or guanidino moiety or derivative thereof. These compounds are useful in vitro for monitoring plasminogen activator levels and in vivo in treatment of conditions which are ameliorated by inhibition of or decreased activity of urokinase and in treating pathologic conditions wherein blood vessel formation is related to a pathologic condition.
- -
-
-