22353-29-3Relevant academic research and scientific papers
Synthesis and Evaluation of Novel Radioligands Based on 3-[5-(Pyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile for Positron Emission Tomography Imaging of Metabotropic Glutamate Receptor Subtype 5
Shimoda, Yoko,Yamasaki, Tomoteru,Fujinaga, Masayuki,Ogawa, Masanao,Kurihara, Yusuke,Nengaki, Nobuki,Kumata, Katsushi,Yui, Joji,Hatori, Akiko,Xie, Lin,Zhang, Yiding,Kawamura, Kazunori,Zhang, Ming-Rong
, p. 3980 - 3990 (2016)
We found out 3-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile analogues as the candidate for positron emission tomography (PET) imaging agents of metabotropic glutamate receptor subtype 5 (mGluR5). Among these compounds, 3-methyl-5-(5-(pyridin-2-yl)-2H-tetrazol-2-yl)benzonitrile (10) exhibited high binding affinity (Ki = 9.4 nM) and moderate lipophilicity (cLogD, 2.4). Subsequently, [11C]10 was radiosynthesized at 25 ± 14% radiochemical yield (n = 11) via C-[11C]methylation of the arylstannyl precursor 15 with [11C]methyl iodide. In vitro autoradiography and PET assessments using [11C]10 showed high specific binding in the striatum and hippocampus, two brain regions enriched with mGluR5. Moreover, test-retest PET studies with [11C]10 indicated high reliability to quantify mGluR5 density, such as the intraclass correlation coefficient (0.90) and Pearson r (0.91) in the striatum of rat brain. We demonstrated that [11C]10 is a useful PET ligand for imaging and quantitative analysis of mGluR5. Furthermore, [11C]10 might be modified using its skeleton as a lead compound.
Asymmetric Radical Process for General Synthesis of Chiral Heteroaryl Cyclopropanes
Deb, Arghya,Ke, Jing,Wang, Xiaoxu,Xu, Yijie,Zhang, X. Peter,Zhu, Yiling
supporting information, p. 11121 - 11129 (2021/08/03)
A highly efficient catalytic method has been developed for asymmetric radical cyclopropanation of alkenes with in situ-generated α-heteroaryldiazomethanes via Co(II)-based metalloradical catalysis (MRC). Through fine-tuning the cavity-like environments of newly-synthesized D2-symmetric chiral amidoporphyrins as the supporting ligand, the optimized Co(II)-based metalloradical system is broadly applicable to α-pyridyl and other α-heteroaryldiazomethanes for asymmetric cyclopropanation of wide-ranging alkenes, including several types of challenging substrates. This new catalytic methodology provides a general access to valuable chiral heteroaryl cyclopropanes in high yields with excellent both diastereoselectivities and enantioselectivities. Combined computational and experimental studies further support the underlying stepwise radical mechanism of the Co(II)-based olefin cyclopropanation involving α- and γ-metalloalkyl radicals as the key intermediates.
Diversity-Oriented Synthesis of 1,2,4-Triazols, 1,3,4-Thiadiazols, and 1,3,4-Selenadiazoles from N-Tosylhydrazones
Wei, Zeyang,Zhang, Qi,Tang, Meng,Zhang, Siyu,Zhang, Qian
supporting information, p. 4436 - 4440 (2021/05/26)
The diversity-oriented synthesis of 1,2,4-triazols, 1,3,4-thiadiazols, and 1,3,4-selenadiazoles from N-tosylhydrazones was developed, and the reactions were general for a wide range of substrates, in which NH2CN, KOCN, KSCN, and KSeCN were used as odorless sources. Two different pathways were proposed, and N-tosylhydrazonoyl chlorides were formed in situ in the presence of NCS.
Visible-Light-Catalyzed in Situ Denitrogenative Sulfonylation of Sulfonylhydrazones
Huang, Xiang,Chen, Xing,Xie, Haisheng,Tan, Zheng,Jiang, Huanfeng,Zeng, Wei
supporting information, p. 6784 - 6788 (2021/09/08)
A photocatalyzed in situ denitrogenative sulfonylation of N-arylsulfonyl hydrazones has been developed. This transformation provides a low-carbon strategy to assemble arylalkyl sulfones in a stepwise denitrogenation/sulfonylation manner.
Iron Hydride Radical Reductive Alkylation of Unactivated Alkenes
Saladrigas, Mar,Bonjoch, Josep,Bradshaw, Ben
supporting information, p. 684 - 688 (2020/01/31)
Iron-catalyzed hydrogen atom transfer-mediated intermolecular C-C coupling reactions between alkenes and tosylhydrazones, followed by in situ cleavage of the tosylhydrazine intermediates using Et3N, are described. The process involves a new strategic bond disconnection resulting in the reductive alkylation of nonactivated alkenes. The reaction is operationally simple, proceeds under mild conditions, and has a wide substrate scope.
KI/TBHP-promoted [3 + 2] cycloaddition of pyrrolo[1,2-a]quinoxalines andN-arylsulfonylhydrazones
He, Jing,Li, Weiwei,Liu, Ping,Wei, Yueting,Yang, Zhen
, p. 3360 - 3366 (2020/05/14)
An efficient KI/TBHP-promoted [3 + 2] cycloaddition of pyrrolo[1,2-a]quinoxalines andN-tosylhydrazones is described. A series of diverse fused [1,2,4]triazolo[3,4-c]quinoxalines was obtained in moderate to good yields with wide functional group tolerance.
Cobalt(II)-based Metalloradical Activation of 2-(Diazomethyl)pyridines for Radical Transannulation and Cyclopropanation
Roy, Satyajit,Das, Sandip Kumar,Chattopadhyay, Buddhadeb
supporting information, p. 2238 - 2243 (2018/02/19)
A new catalytic method for the denitrogenative transannulation/cyclopropanation of in-situ-generated 2-(diazomethyl)pyridines is described using a cobalt-catalyzed radical-activation mechanism. The method takes advantage of the inherent properties of a CoIII-carbene radical intermediate and is the first report of denitrogenative transannulation/cyclopropanation by a radical-activation mechanism, which is supported by various control experiments. The synthetic benefits of the metalloradical approach are showcased with a short total synthesis of (±)-monomorine.
Tetrazole-Based Probes for Integrated Phenotypic Screening, Affinity-Based Proteome Profiling, and Sensitive Detection of a Cancer Biomarker
Cheng, Ke,Lee, Jun-Seok,Hao, Piliang,Yao, Shao Q.,Ding, Ke,Li, Zhengqiu
supporting information, p. 15044 - 15048 (2017/11/20)
Target-identification phenotypic screening has been a powerful approach in drug discovery; however, it is hindered by difficulties in identifying the underlying cellular targets. To address this challenge, we have combined phenotypic screening of a fully functionalized small-molecule library with competitive affinity-based proteome profiling to map and functionally characterize the targets of screening hits. Using this approach, we identified ANXA2, PDIA3/4, FLAD1, and NOS2 as primary cellular targets of two bioactive molecules that inhibit cancer cell proliferation. We further demonstrated that a panel of probes can label and/or image annexin A2 (a cancer biomarker) from different cancer cell lines, thus providing opportunities for potential cancer diagnosis and therapy.
Potent antimicrobial agents against azole-resistant fungi based on pyridinohydrazide and hydrazomethylpyridine structural motifs
Backes, Gregory L.,Jursic, Branko S.,Neumann, Donna M.
, p. 3397 - 3407 (2015/08/03)
Abstract Schiff base derivatives have recently been shown to possess antimicrobial activity, and these derivatives include a limited number of salicylaldehyde hydrazones. To further explore this structure-activity relationship between salicylaldehyde hydrazones and antifungal activity, we previously synthesized and analyzed a large series of salicylaldehyde and formylpyridinetrione hydrazones for their ability to inhibit fungal growth of both azole-susceptible and azole-resistant species of Candida. While many of these analogs showed excellent growth inhibition with low mammalian cell toxicity, their activity did not extend to azole-resistant species of Candida. To further dissect the structural features necessary to inhibit azole-resistant fungal species, we synthesized a new class of modified salicylaldehyde derivatives and subsequently identified a series of modified pyridine-based hydrazones that had potent fungicidal antifungal activity against multiple Candida spp. Here we would like to present our synthetic procedures as well as the results from fungal growth inhibition assays, mammalian cell toxicity assays, time-kill assays and synergy studies of these novel pyridine-based hydrazones on both azole-susceptible and azole-resistant fungal species.
Fast alpha nucleophiles: Structures that undergo rapid hydrazone/oxime formation at neutral pH
Kool, Eric T.,Crisalli, Pete,Chan, Ke Min
supporting information, p. 1454 - 1457 (2014/04/03)
Hydrazones and oximes are widely useful structures for conjugate formation in chemistry and biology, but their formation can be slow at neutral pH. Kinetics studies were performed for a range of structurally varied hydrazines, and a surprisingly large variation in reaction rate was observed. Structures that undergo especially rapid reactions were identified, enabling reaction rates that rival orthogonal cycloaddition-based conjugation chemistries.
