- Synthesis, Docking, and Biological activities of novel Metacetamol embedded [1,2,3]-triazole derivatives
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ERα controls the breast tissue development and progression of breast cancer. In our search for novel compounds to target Estrogen Receptor Alpha Ligand-Binding Domain, we identified “N-(3-((1H-1,2,3-triazol-4-yl)methoxy)phenyl)acetamide” derivatives as lead compounds. The Docking studies indicated good docking score for Metacetamol derivatives when docked into the 1XP6. A series of metacetamol derivatives have been synthesized, characterized and evaluated for cytotoxicity, anti bacterial and anti oxidant activities. Among the tested twelve hybrid compounds, “7a, 7g, 7h and 7i” derivatives showed promising cytotoxicity with IC50 value of 50 value of 30 μM, whereas Compounds “7a, 7b, 7c, 7d, 7g, 7j, 7k and 7l” showed moderate anti bacterial activity with the MIC value of 300 μM.
- Battu, Satyanarayana,Joolakanti, Hima Bindhu,Kamepalli, Ramanjaneyulu,Miryala, Jeevanreddy
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- [1,3]-Claisen rearrangement via removable functional group mediated radical stabilization
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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.
- Alam, Md Nirshad,Dash, Soumya Ranjan,Mukherjee, Anirban,Pandole, Satish,Marelli, Udaya Kiran,Vanka, Kumar,Maity, Pradip
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supporting information
p. 890 - 895
(2021/02/01)
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- 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
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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.
- Gaikwad, Nikhil B.,Bansode, Sapana,Biradar, Shankar,Ban, Mayuri,Srinivas, Nanduri,Godugu, Chandraiah,Yaddanapudi, Venkata M.
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- Visible-Light-Driven Oxidative Mono- and Dibromination of Benzylic sp 3 C-H Bonds with Potassium Bromide/Oxone at Room Temperature
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Benzylic sp 3 C-H bonds have been successfully brominated with potassium bromide by using Oxone as an oxidant in water/dichloromethane under visible light at room temperature. Toluene, ethylbenzene and other alkylbenzenes bearing an electron-withdrawing group, such as Br, Cl, COMe, CO 2 Et, CO 2 H, CN or NO 2, provide the corresponding benzylic monobromides in good to excellent yields in this reaction. Dibromides can also be produced in the presence of excess potassium bromide in a prolonged reaction time. Control of the illuminance of visible light (~500 lux) is crucial to achieving both high yield and high selectivity in these brominations. Mono- and difluorides can be conveniently prepared through nucleophilic substitutions of the benzylic bromides with potassium fluoride.
- Zhao, Mengdi,Li, Meiqi,Lu, Wenjun
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supporting information
p. 4933 - 4939
(2018/12/14)
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- Method for preparing benzyl bromide
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The invention provides a method for preparing benzyl bromide. The method comprises the following steps: by taking bromine released from a redox reaction between bromates and negative bromide ions in the presence of an acid as a bromine source in an organic solvent, carrying out a benzyl radical substitution reaction with a methylbenzene compound shown as a formula I under initiation of an initiator, thereby obtaining a corresponding benzyl bromide compound shown a formula II, wherein in the formula II, m represents the number of Br and is equal to 1 or 2; when m is equal to 1, the formula II shows a benzyl monobromo compound; and when m is equal to 2, the formula II shows a benzyl dibromo compound. The reaction is carried out in an organic solvent, the initiator is combined and used, the radical substitution reaction is high in selectivity and wide in substrate application range, the substituent group replacing methylbenzene may be an electron-withdrawing group or an electron-donating group and can give extremely high yield on strong electron-donating groups (such as methoxy group). Moreover, the method disclosed by the invention is also applicable to preparation of benzyl dibromo compounds, and the product yield is high.
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Paragraph 0043-0045
(2017/10/05)
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- Synthesis of Novel Triazole-incorporated Isatin Derivatives as Antifungal, Antitubercular, and Antioxidant Agents and Molecular Docking Study
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A library of 1,2,3-triazoles efficiently prepared via click chemistry and evaluated for their antifungal, antitubercular, antioxidant, cytotoxicity, molecular docking and ADME prediction.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Nawale, Laxman,Arkile, Manisha,Sarkar, Dhiman,Shingate, Bapurao B.
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p. 413 - 421
(2017/02/03)
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- Synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent
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In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and M. bovis BCG, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34-29.37 μg/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG. The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC50 range = 14.14-47.11 μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Arkile, Manisha,Khedkar, Vijay M.,Jadhav, Nandadeep,Sarkar, Dhiman,Shingate, Bapurao B.
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p. 561 - 569
(2016/01/09)
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- Synthesis, biological evaluation and molecular docking of novel coumarin incorporated triazoles as antitubercular, antioxidant and antimicrobial agents
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A series of new coumarin-based 1,2,3-triazole derivatives were designed, synthesized and evaluated for their antitubercular activity in vitro against Mycobacterium tuberculosis H37Ra, antioxidant activity by DPPH radical scavenging assay, antimicrobial activity in vitro against three gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus and Bacillus cereus) and three gram-negative bacteria (Escherichia coli, Pseudomonas fluorescens and Flavobacterium devorans as well as three fungi (Aspergillus niger, Penicillium chrysogenum and Curvularia lunata). The bioactive assay showed that some synthesized coumarin triazoles displayed comparable or even better antitubercular, antioxidant, antibacterial and antifungal efficacy in comparison with reference drugs. Furthermore, docking study has been performed against DprE1 enzyme of M. tuberculosis that showed good binding interactions. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential to build up as good oral drug candidates. Graphical Abstract: New coumarin-based 1,2,3-triazole derivatives were designed, synthesized and evaluated for their antitubercular, antioxidant, antibacterial and antifungal activity. Some of the coumarin-based triazole derivatives displayed comparable or even better efficacy in comparison with reference drugs. Molecular docking study has been performed against DprE1 enzyme of Mycobacterium tuberculosis showed good binding interactions.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Shingate, Bapurao B.,Kalam Khan, Firoz A.,Sangshetti, Jaiprakash N.,Khedkar, Vijay M.,Nawale, Laxman,Sarkar, Dhiman,Navale, Govinda R.,Shinde, Sandip S.
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p. 790 - 804
(2016/03/08)
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- 1,2,3-Triazole tethered acetophenones: Synthesis, bioevaluation and molecular docking study
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A small focused library of eighteen new 1,2,3-triazole tethered acetophenones has been efficiently prepared via click chemistry approach and evaluated for their antifungal and antioxidant activity. The antifungal activity was evaluated against five human pathogenic fungal strains: Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger, and Cryptococcus neoformans. Among the synthesized compounds, 9c, 9i, and 9p found to be more potent antifungal agents that the reference standard. These 1,2,3-triazole based derivatives were also evaluated for antioxidant activity, and compound 9h was found to be the most potent antioxidant as compared to the standard drug. Furthermore, molecular docking study of the newly synthesized compounds was performed and results showed good binding mode in the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential as good oral drug candidates.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Khedkar, Vijay M.,Jha, Prakash C.,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
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p. 1058 - 1063
(2016/07/29)
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- 1,2,3-Triazole incorporated coumarin derivatives as potential antifungal and antioxidant agents
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A series of novel ethyl-7-((1-(benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxylates 8a-h as potential antifungal agents were synthesized via click chemistry. The antifungal activity was evaluated against five human pathogenic fungal strains, such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Compound 8c, 8d, 8e and 8h were found to be equipotent against C. albicans when compared with miconazole and compound 8f was found to be two-fold more active compared with miconazole and equipotent to fluconazole against C. albicans. The coumarin-based triazole derivatives were also evaluated for antioxidant activity and compound 8a was found to be potent antioxidant when compared with standard drug. Furthermore, molecular docking study of the newly synthesized compounds was performed and results showed good binding mode in the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential to build up as good oral drug candidates.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
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p. 295 - 301
(2018/03/22)
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- 1,2,3-Triazole derivatives as antitubercular agents: synthesis, biological evaluation and molecular docking study
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Searching for new active molecules against Mycobacterium tuberculosis (MTB) H37Ra, a small focused library of 1,2,3-triazoles has been efficiently prepared via a click chemistry approach. The newly synthesized compounds were tested against drug-sensitive MTB. Several derivatives were found to be promising inhibitors of MTB characterized by lower MIC values (5.8-29.9 μg mL-1). Among all the synthesized 31 compounds, 15e was the most active compound against MTB. Based on the results from the anti-tubercular activity, SAR for the synthesized series has been developed. The active compounds from the anti-tubercular study were further tested for anti-proliferative activity against THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity against these three cell lines except THP-1 at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activities with an IC50 range of 10.1-37.3 μg mL-1. The molecular docking study of the synthesized compounds was performed against the DprE1 enzyme of MTB to understand the binding interactions. Moreover, the synthesized compounds were also analysed for ADME properties and all the experimental results promote us to consider this series as a starting point for the development of novel and more potent anti-tubercular agents in the future.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Nawale, Laxman,Sarkar, Dhiman,Kalam Khan, Firoz A.,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
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p. 1104 - 1116
(2015/06/25)
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- Palladium(0)-catalyzed cyclopropanation of benzyl bromides via C(sp 3)-H bond activation
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A novel and highly efficient Pd(0)-catalyzed domino reaction to prepare cyclopropane derivatives has been established. The process involves a Heck-type coupling reaction and a C(sp3)-H bond activation. Preliminary DFT calculations suggest that a four-membered palladacycle intermediate is involved. This journal is the Partner Organisations 2014.
- Mao, Jiangang,Zhang, Shuo-Qing,Shi, Bing-Feng,Bao, Weiliang
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p. 3692 - 3694
(2014/04/03)
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- Synthesis of 2,4-unsubstituted quinoline-3-carboxylic acid ethyl esters from arylmethyl azides via a domino process
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A convenient synthesis of 2,4-unsubstituted quinoline-3-carboxylic acid ethyl esters via a domino process is described. The synthesis employs arylmethyl azides as the precursor which undergoes an acid-promoted rearrangement to give an N-aryl iminium ion. Following the addition with ethyl 3-ethoxyacrylate, intramolecular electrophilic aromatic substitution, elimination and subsequent oxidation, the quinoline products were obtained in moderate to excellent yields.
- Tummatorn, Jumreang,Thongsornkleeb, Charnsak,Ruchirawat, Somsak,Gettongsong, Tanita
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supporting information
p. 1463 - 1467
(2013/05/08)
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- Catalyst and solvent-free bromination of toluene derivatives by HBr-H 2O2 with visible-light photocatalysis using a continuous-flow micro reactor
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The efficiency of the bromination of toluene derivatives has been improved significantly by utilising a combination of hydrogen peroxide (30%) and hydrogen bromide (40%) in a continuous-flow micro reactor. This catalyst and solvent-free reaction takes place by visible-light photocatalysis.
- Yu, Wu-Bin,Yu, Dong-Ping,Zheng, Ming-Ming,Shan, Shu-Ting,Li, Yu-Jin,Gao, Jian-Rong
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experimental part
p. 258 - 260
(2012/09/22)
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- Polyvinylpyrrolidone-bromine complex: An efficient polymeric reagent for selective preparation of benzyl bromides in the presence of hexamethyldisilane
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Benzylic bromides were conveniently obtained in high yields via the reaction of the corresponding alcohols with crosslinked polyvinylpyrrolidone- bromine complex (PVPP-Br2)/hexamethyldisilane in chloroform at reflux condition. Selective conversion of benzyl alcohol to benzyl bromide in the presence of primary aliphatic alcohols, e.g. 2-phenylethanol was also achieved.
- Mokhtary, Masoud,Lakouraj, Moslem M.
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p. 305 - 309
(2012/10/29)
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- High selectively oxidative bromination of toluene derivatives by the H 2O2-HBr system
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An aqueous solution of hydrogen peroxide and hydrogen bromide illuminated by a 60 W incandescent light bulb serves as a source of bromine radicals. Various substituted toluenes (NO2, Cl, Br, H, CH3) were high selectively brominated at the benzyl position for monobromination in CH2Cl2 at ice water with catalyst free. This simple but effective bromination of toluene derivatives with an aqueous H2O 2-HBr system is characterized with the use of inexpensive reagents and a lower impact on the environment, which make it a good alternative to the existing bromination methods.
- Ju, Jie,Li, Yu Jin,Gao, Jian Rong,Jia, Jian Hong,Han, Liang,Sheng, Wei Jian,Jia, Yi Xia
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experimental part
p. 382 - 384
(2012/01/05)
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- Benzylic bromination of toluene derivatives with boron tribromide
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A facile method for the benzylic bromination of toluene derivatives was developed. Various substituted toluenes were brominated with boron tribromide as bromine source in carbon tetrachloride at room temperature, affording their corresponding benzyl bromides in good yields.
- Chen, Hongbiao,Shen, Litao,Lin, Yuanbin
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experimental part
p. 998 - 1003
(2010/05/18)
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- Visible-light-promoted Wohl-Ziegler functionalization of organic molecules with N-bromosuccinimide under solvent-free reaction conditions
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The visible-light-induced transformation of toluenes with N-bromosuccinimide (NBS) under solvent-free reaction conditions (SFRC) was studied. The reaction took place in spite of the very restricted molecular motion; toluenes could be regioselectively converted to benzyl bromides. Selective radical-chain reactions with NBS were carried out in liquid/liquid and in solid/solid systems; furthermore, reactions could be performed in the presence of air. The radical scavenger TEMPO (=2,2,6,6-tetramethylpiperidin-1- yloxy) completely suppressed the side-chain bromination of toluenes with NBS under SFRC. Electron-withdrawing groups decreased the reactivity of the toluenes, and the Hammett reaction constant ρ+ = -1.7 indicated involvement of polar radical intermediates with electrophilic character.
- Jereb, Marjan,Zupan, Marko,Stavber, Stojan
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scheme or table
p. 555 - 566
(2009/09/06)
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- Antineoplastic pyrrolo[4,3,2-de]quinolin-8(1H)-ones
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The invention discloses certain antitumor pyrrolo[4,3,2-de]quinolin-8(1H)-ones isolated from the Fijian marine sponge Z. cf. marsailis and structurally modified compounds thereof and pharmaceutical compositions.
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- NUCLEOPHILIC SUBSTITUTION REACTION OF BENZYL BROMIDE WITH N,N-DIMETHYLANILINE: SIGNIFICANCE OF EQUILIBRIUM CROSS-INTERACTION CONSTANT
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Kinetic studies on the reversible reactions of benzyl bromides with N,N-dimethylanilines were carried out for both the forward (kf) and reverse (kr) directions.The equilibrium constants, K were calculated using the ratio kf//kr and the equilibrium cross-interaction constant, ρeXY was determined.The ρeXY value was shown to represent a maximum intensity of interactions between substituents X and Y through covalent bonds within a molecule.The normalized values of ρX (ρnuc) and ρXY indicate that in the transition state the fractional development or loss of polar and resonance interactions in the benzyl system are imbalanced or non-perfectly synchronized.In the forward reaction the fractional loss of resonance interaction becomes enhanced, whereas in the reverse reaction the fractional development of resonance interaction lags behind the corresponding changes of polar interaction by ca 45percent.
- Lee, Ikchoon,Park, Yong Kyun,Huh, Chul,Lee, Hai Whang
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p. 555 - 560
(2007/10/02)
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- ORGANIC PHOSPHORUS COMPOUNDS 91. SYNTHESIS AND PROPERTIES OF 1-AMINO-2-ARYLETHYLPHOSPHONIC AND -PHOSPHINIC ACIDS AS WELL AS -PHOSPHINE OXIDES
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The preparation, physical and spectroscopic properties of 1-amino-2-arylethylphosphonic, and -phosphinic acids as well as -phosphine oxides, the phosphorus analogues of phenylalanine are described, and the reactions of 1-amino-2-(4-fluorophenyl)ethylphosphonates with acetals, isocyanides, esters, acid anhydrides, activated aromatic nitro- and halogen compounds, and with N-protected alanine are reported.It is shown that several of the 1-amino-2-arylethylphosphonic acids are strong inhibitors of PAL and anthocyanin synthesis and also are quite active botryticides.Among the active compounds were 1-amino-2-(4-fluorophenyl)ethylphosphonic acid, 3f, and the methyl-substituted compounds 3k, 3l, and 3m.The fluoroderivative 3f was also effective as a seed-dressing agent in barley showing a 100percent protection against the fungus Fusarium nivale at 600 ppm.
- Maier, Ludwig
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- MECHANISMS OF FREE-RADICAL REACTIONS. XX. REACTIVITY IN THE FREE-RADICAL HALOGENATION REACTIONS OF ARYLFLUOROALKANES
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The free-radical chlorination and bromination of meta- and para-substituted benzyl fluorides and 1,1-difluoro-2-phenylethane and also the chlorination of 1-fluoro-2-arylethanes by phenylchloroiodonium chloride and the bromination of meta- and para-substituted benzyl bromides were studied by the method of competing reactions.In all cases a good correlation is observed between log krel and the Brown ?+ constants.In cases where change in the reactivity in the transition from one reaction series to another is due mainly to the polar effect of the substituent whilethe selectivity is measured in relation to the polar effect direct relationships are observed between the reactivity and the selectivity.
- Dneprovskii, A. S.,Eliseenkov, E. V.
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p. 711 - 719
(2007/10/02)
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- Polar Radicals. 14. On the Mechanism of Trialkylstannane Reductions. Positive ρ Values for the Tri-n-butylstannane Reduction of Benzyl Halides. A Correlation with ?-
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The relative reactivities towards reduction by tri-n-butylstannane of a series of substituted benzyl halides have been determined.The order of reactivity was shown to be I > Br > Cl, the same as that reported for alkyl halide reductions.Under the reaction conditions (90 deg C, benzene as solvent, benzoyl peroxide initiation), both aralkyl and alkyl fluorides were shown to be completely unreactive.Activation energies were estimated for the direct abstraction of halogen by tri-n-butyl radicals, and on the basis of these estimates all of the halogens would be predicted to readily undergo abstraction.To explain the non-reactivity of the fluorides several other mechanisms were considered: reversible tin radical addition to the halogen to form an intermediate with an expanded octet, and a free radical chain mechanism involving an electron-transfer reaction between the trialkyltin radical and the benzyl halide. The benzyl halide reductions showed excellent Hammett correlations with positive ρ values; all of these correlations were obtained using ?- substituent constants.The demonstration (the first ever reported) that ?- substituent constants correlate with the relative reactivities for reduction infers that bond breaking takes place in the transition state for the reaction.The magnitudes of the ρ values were not found, as were expected, to be in the inverse order of the relative reactivities: ρ for the iodides (+0.81), for the bromides (+0.17), and for the chlorides (+0.34).To explain the anomalously high value of ρ found for the iodide reduction, it was suggested that the benzyl iodides underwent reduction by a different mechanism than the chlorides and the bromides.The relative rates of reduction of the benzyl iodides in a more polar solvent than benzene, acetonitrile, showed decreased sensitivity to substituents, whereas the reduction of the bromides and chlorides was relatively insensitive to solvent effects.
- Blackburn, Edward V.,Tanner, Dennis D.
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p. 692 - 697
(2007/10/02)
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- Amino-benzimidazole derivatives
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Amino-benzimidazole derivatives of the structure STR1are provided which are useful as anti-inflammatory agents. In addition, a method for preparing such compounds, pharmaceutical compositions containing such compounds, and methods for using such pharmaceutical compositions in the treatment of inflammation are taught.
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