589-15-1Relevant articles and documents
Synthesis, inhibition properties against xanthine oxidase and molecular docking studies of dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives
Yagiz, Güler,Noma, Samir Abbas Ali,Altundas, Aliye,Al-khafaji, Khattab,Taskin-Tok, Tugba,Ates, Burhan
, (2021/01/28)
This study focused on synthesis various dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives under the conditions of green chemistry without the use of solvent and catalysts. Their inhibition properties were also investigated on xanthine oxidase (XO) activity. All dimethanol and dicarboxylate derivatives exhibited significant inhibition activities with IC50 values ranging from 0.71 to 2.25 μM. Especially, (1-(3-bromobenzyl)-1H-1,2,3-triazole-4,5-diyl)dimethanol (5c) and dimethyl 1-(4-chlorobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate (6 g) compounds were found to be the most promising derivatives on the XO enzyme inhibition with IC50 values 0.71 and 0.73 μM, respectively. Moreover, the double docking procedure was to evaluate compound modes of inhibition and their interactions with the protein (XO) at atomic level. Surprisingly, the docking results showed a good correlation with IC50 [correlation coefficient (R2 = 0.7455)]. Also, the docking results exhibited that the 5c, 6f and 6 g have lowest docking scores ?4.790, ?4.755, and ?4.730, respectively. These data were in agreement with the IC50 values. These results give promising beginning stages to assist in the improvement of novel and powerful inhibitor against XO.
[1,3]-Claisen rearrangement via removable functional group mediated radical stabilization
Alam, Md Nirshad,Dash, Soumya Ranjan,Mukherjee, Anirban,Pandole, Satish,Marelli, Udaya Kiran,Vanka, Kumar,Maity, Pradip
supporting information, p. 890 - 895 (2021/02/01)
A thermal O-to-C [1,3]-rearrangement of α-hydroxy acid derived enol ethers was achieved under mild conditions. The 2-aminothiophenol protection of carboxylic acids facilitates formation of the [1,3] precursor and its thermal rearrangement via stabilization of a radical intermediate. Experimental and theoretical evidence for dissociative radical pair formation, its captodative stability via aminothiophenol, and a unique solvent effect are presented. The aminothiophenol was deprotected from rearrangement products as well as after derivatization to useful synthons.
New 3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one-based triazole derivatives: Design, synthesis, and biological evaluation as antiproliferative and apoptosis-inducing agents
Gaikwad, Nikhil B.,Bansode, Sapana,Biradar, Shankar,Ban, Mayuri,Srinivas, Nanduri,Godugu, Chandraiah,Yaddanapudi, Venkata M.
, (2021/08/07)
A series of 1,2,3-triazole derivatives based on the quinoline–benzimidazole hybrid scaffold was designed, synthesized, and screened against a panel of NCI-60 humanoid cancer cell lines for in vitro cytotoxicity evaluation, which revealed that compound Q6 was the most potent cytotoxic agent with excellent GI50, TGI, and LC50 values on multiple cancer cell lines. Q6 was tested further on the BT-474 breast cancer line to evaluate the mechanism of action. Preliminary screening studies based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that compound Q6 had an excellent antiproliferative effect against human breast cancer cells, BT-474, with IC50 values of 0.59 ± 0.01 μM. The detailed study based on the acridine orange/ethidium bromide staining (AO/EB) and the 4′,6-diamidino-2-phenylindole (DAPI) assay suggested that the antiproliferative activity shown was due to the induction of apoptosis on exposure to Q6. Further, DCFDA staining showed the generation of reactive oxygen species, altering the mitochondrial potential and leading to the initiation of apoptosis. This was further supported by JC-1 staining, indicating that this scaffold can contribute to the development of more potent derivatives.
Continuous Synthesis and Separation ofp-Bromobenzyl Bromide Using Atom-Efficient Bromination ofp-Bromotoluene without Any Organic Effluent: Potential for Green Industrial Practice
Sancheti, Sonam V.,Yadav, Ganapati D.
, p. 2071 - 2080 (2021/09/13)
This work focuses on the bromination ofp-bromotoluene (PBT) using different brominating agents such as liquid Br2, NaBr-NaBrO3, NaBr-NaBrO3-NaCl, NaBr-H2O2, and HBr-H2O2. NaBr-NaBrO3-NaCl is an eco-friendly brominating agent obtained from a bromine recovery plant. Both NaBr-NaBrO3and NaBr-NaBrO3-NaCl were found to be nonhazardous and efficient brominating agents. Pure NaBr-NaBrO3resulted in the best PBT conversion with 79.7% Br atom efficiency in water and 98.2% average Br atom efficiency using dichloroethane as a solvent. Dichloroethane is de facto no longer used in the US and Europe and is not eco-friendly; the process with water as a solvent is the best. The substrate to active bromine molar ratio of 3:1 was found to be sufficient to get the maximum selectivity ofp-bromobenzyl bromide (PBBB). The low-temperature crystallization method was used for separation cum purification of the product. Unreacted PBT was recycled along with the dibromo byproduct obtained. The dibromo product, which was built up gradually in the reaction mixture over 10 successive batches, was converted back into PBBB/PBT through NaBH4treatment of the mother liquor. This continuous process is highly sustainable and produces zero organic waste, making it potentially attractive toward green industrial implementation.
NOVEL APOPTOSIS SIGNAL-REGULATING KINASE 1 INHIBITORS
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, (2021/01/23)
The present invention relates to inhibitors of apoptosis signal-regulating kinase 1 ("ASK1"), a process for synthesis of the compounds of the present invention, composition comprising the compounds and use of the compounds for inhibition of ASK1.
Thiourea-Catalyzed C?F Bond Activation: Amination of Benzylic Fluorides
Houle, Camille,Savoie, Paul R.,Davies, Clotilde,Jardel, Damien,Champagne, Pier Alexandre,Bibal, Brigitte,Paquin, Jean-Fran?ois
supporting information, p. 10620 - 10625 (2020/07/24)
We describe the first thiourea-catalyzed C?F bond activation. The use of a thiourea catalyst and Ti(OiPr)4 as a fluoride scavenger allows the amination of benzylic fluorides to proceed in moderate to excellent yields. Preliminary results with S- and O-based nucleophiles are also presented. DFT calculations reveal the importance of hydrogen bonds between the catalyst and the fluorine atom of the substrate to lower the activation energy during the transition state.
Decarboxylative Bromination of Sterically Hindered Carboxylic Acids with Hypervalent Iodine(III) Reagents
Kanazawa, Junichiro,Koyamada, Kenta,Miyamoto, Kazunori,Uchiyama, Masanobu,Watanabe, Ayumi
supporting information, p. 1328 - 1334 (2020/08/14)
Sterically hindered three-dimensional (3D) alkyl halides are promising precursors for various reactions; however, they are difficult to synthesize via conventional reactions. We present an efficient and practical method for decarboxylative bromination of sterically hindered 3D aliphatic carboxylic acids using commercially available (diacetoxyiodo)benzene and potassium bromide, one of the most stable and cheapest bromine sources in nature. The present method features a metal-free/Br2-free system, mild reaction conditions, one-pot operation under air at room temperature, wide functional group compatibility, and gram-scale synthetic capability. This highly efficient reaction cleanly converts a broad range of carboxylic acids, the most inexpensive and readily available sources of highly strained/naturally occurring/drug-related scaffolds, into the corresponding alkyl bromides in good to high yields.
Promotion of Appel-type reactions by N-heterocyclic carbenes
Hussein, Mohanad A.,Nguyen, Thanh Vinh
supporting information, p. 7962 - 7965 (2019/07/12)
N-Heterocyclic carbenes (NHCs) have been extensively used as a versatile class of catalysts and ligands in organocatalytic and organometallic chemistry. However, there are only a small number of synthetic applications where they act as reagents. Here we demonstrate that NHCs can be used as stoichiometric redox reagents for Appel-type halogenation reactions of alcohols. This new reactivity reveals a fresh and interesting aspect and enriches the chemistry of NHCs in an underexplored area. The potential of performing this chemical transformation at the catalytic level using an NHC-oxide derivative is also investigated.
THERAPEUTIC COMPOUNDS AND METHODS TO TREAT INFECTION
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Paragraph 0418-0419, (2019/02/13)
Disclosed herein are compounds of formula I: or a salt thereof and compositions comprising a compound of formula I or a pharmaceutically acceptable salt thereof. Also disclosed herein are methods for treating or preventing a bacterial infection in an animal comprising administering to the animal a compound of formula I or a pharmaceutically acceptable salt thereof, alone or in combination with a bacterial efflux pump inhibitor.
Design, synthesis and biological evaluation of low molecular weight CXCR4 ligands
Sakyiamah, Maxwell M.,Kobayakawa, Takuya,Fujino, Masayuki,Konno, Makoto,Narumi, Tetsuo,Tanaka, Tomohiro,Nomura, Wataru,Yamamoto, Naoki,Murakami, Tsutomu,Tamamura, Hirokazu
supporting information, p. 1130 - 1138 (2019/02/16)
The chemokine receptor CXCR4/stromal cell-derived factor-1 (SDF-1: CXCL12) signaling axis represents a crucial drug target due to its relevance to several diseases such as HIV-1 infection, cancer, leukemia, and rheumatoid arthritis. With the aim of enhancing the binding affinity and anti-HIV activity of a potent CXCR4 ligand as a lead, 23 low molecular weight compounds containing dipicolylamine (Dpa) and cyclam cationic moieties with varying spacers and spatial positioning were designed, synthesized and biologically evaluated. All of the synthesized compounds screened at 1.0 μM in the NanoBRET assay system exhibited >70% inhibition of the binding of a competitive probe TAMRA-Ac-TZ14011 (10 nM) to CXCR4 in the presence of zinc (II) ion. Furthermore, selected compounds 3, 8, 9, 19 and 21 with spatial distances between the next carbon to Dpa and the next carbon to cyclam within the range of 6.5–7.5 ? showed potent binding affinity selective for CXCR4 with IC50 values of 1.6, 7.9, 5.7, 3.5 and 4.5 nM, respectively, with corresponding high anti-HIV activity with EC50s of 28, 13, 21, 28 and 61 nM, respectively, in the presence of zinc (II) ion. Some compounds with remarkably more potent CXCR4-binding affinity than that of an initial lead were obtained. These compounds interact with different but overlapping amino acid residues of CXCR4. The present studies have developed new low molecular weight CXCR4 ligands with high CXCR4-binding and anti-HIV activities, which open avenue into the development of more potent CXCR4 ligands.
