cas 51012-64-7, 2-Bromo-3-methylacetophenone

Articles about 51012-64-7Total 61 be found

Article title
Article abstract
Author
Journal number and time
Download

High Chemo-/Stereoselectivity for Synthesis of Polysubstituted Monofluorinated Pyrimidyl Enol Ether Derivatives
A novel intramolecular Smiles rearrangement of α-fluoro-β-keto-pyrimidylsulfones (usually used as a carbon nucleophile) was developed, providing a versatile avenue for synthesis of tri/tetra-substituted monofluorinated pyrimidyl enol ethers. Among these, diverse (Z)-monofluorovinylsulfones and sulfinates were efficiently assembled by adding extra electrophile and fine-tuning reaction conditions. The process is triggered by a keto-enol tautomerism from enol oxyanion to pyrimidine 2-carbon, completely different from the classical carbon nucleophilic addition reaction approach.
Kang, Lei,Wang, Fang,Zhang, Jinlong,Yang, Huameng,Xia, Chungu,Qian, Jinlong,Jiang, Gaoxi
supporting information
p. 1669 - 1674
(2021/03/08)

Base-Catalyzed Intramolecular Defluorination/O-Arylation Reaction for the Synthesis of 3-Fluoro-1,4-oxathiine 4,4-Dioxide
A novel process involving base-catalyzed intramolecular defluorination/O-arylation of readily available α-fluoro-β-one-sulfones was realized and provided a series of 3-fluoro-1,4-oxathiine 4,4-dioxide derivatives in good to excellent yields. Unlike traditional defluorination reactions with stoichiometric base as the deacid reagent, this process is triggered by a catalytic amount of base (TMG: tetramethylguanidine) and molecular sieves serve as both an adsorbent to remove HF acid and an activator to assist C-F bond cleavage.
Kang, Lei,Zhang, Jinlong,Yang, Huameng,Qian, Jinlong,Jiang, Gaoxi
supporting information
p. 785 - 789
(2021/04/09)

Structure-activity relationship studies in substituted sulfamoyl benzamidothiazoles that prolong NF-κB activation
In the face of emerging infectious diseases, there remains an unmet need for vaccine development where adjuvants that enhance immune responses to pathogenic antigens are highly desired. Using high-throughput screens with a cell-based nuclear factor κB (NF-κB) reporter assay, we identified a sulfamoyl benzamidothiazole bearing compound 1 that demonstrated a sustained activation of NF-κB after a primary stimulus with a Toll-like receptor (TLR)-4 agonist, lipopolysaccharide (LPS). Here, we explore systematic structure–activity relationship (SAR) studies on compound 1 that indicated the sites on the scaffold that tolerated modification and yielded more potent compounds compared to 1. The selected analogs enhanced release of immunostimulatory cytokines in the human monocytic cell line THP-1 cells and murine primary dendritic cells. In murine vaccination studies, select compounds were used as co-adjuvants in combination with the Food and Drug Administration approved TLR-4 agonistic adjuvant, monophosphoryl lipid A (MPLA) that showed significant enhancement in antigen-specific antibody titers compared to MPLA alone. Additionally, our SAR studies led to identification of a photoaffinity probe which will aid the target identification and mechanism of action studies in the future.
Belsuzarri, Masiel,Carson, Dennis A.,Chan, Michael,Chu, Paul J.,Corr, Maripat,Cottam, Howard B.,Hayashi, Tomoko,Lao, Fitzgerald S.,Nan, Jason,Saito, Tetsuya,Sato-Kaneko, Fumi,Shukla, Nikunj M.,Yao, Shiyin
(2021/07/19)

Microwave-assisted synthesis and luminescent activity of imidazo[1,2-a]pyridine derivatives
In this work, a series of phenacyl bromide derivatives was synthesized and employed as key intermediate for the synthesis of substituted imidazo[1,2-a]pyridines. First, phenacyl bromide molecules were obtained from the bromination reaction of acetophenones assisted by microwave irradiation, obtaining the products 4a-v in a 15 minutes reaction with yields in the range of 50% to 99%. Subsequently, the conjugation of these molecules with 2-aminopyridine conduced to the production of imidazo[1,2-a]pyridine derivatives (7a-v) in a 60-second reaction with yields of 24% to 99%. Improved yields were determined with respect to those obtained with more tedious methodologies like thermally and mechanically assisted routes. Intense luminescence emissions in the purple and blue regions of the electromagnetic spectra were observed under UV excitation according to the nature of the substituents. This environmentally friendly methodology is expected to constitute an important class of organic compounds for the development of biomarkers, photochemical sensors, and medicinal applications.
Rodríguez, Juan C.,Maldonado, Rony A.,Ramírez-García, Gonzalo,Díaz Cervantes, Erik,de la Cruz, Fabiola N.
p. 2279 - 2287
(2020/03/16)

MAT2A INHIBITORS
Disclosed herein are compounds of Formula (I), that inhibit Methionine Adenosyltransferase 2A (MAT2A) activity. In particular, the invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the
-
Paragraph 0141-0142

(2020/08/28)

Pd-Catalyzed Decarboxylative Olefination: Stereoselective Synthesis of Polysubstituted Butadienes and Macrocyclic P-glycoprotein Inhibitors
The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.
Chen, Xiangyang,Hao, Jiping,Houk, K. N.,Li, Yingzi,Lou, Liguang,Quan, Haitian,Song, Bichao,Wang, Lu,Xia, Yuanzhi,Xie, Peipei,Xu, Zhongliang,Yang, Weibo
supporting information
p. 9982 - 9992
(2020/06/27)

Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
(2020/10/08)

Design and synthesis of new donepezil analogs derived from arylpiperazine scaffold as acetylcholinesterase inhibitors
Newly synthesized 4-substituted phenyl-2-(4-substituted phenylpiperazine-1-yl)thiazole derivatives (4a–v) were evaluated in terms of their acetylcholinesterase (AChE) inhibition activities. Twenty-two compounds were tested against AChE at six different concentrations that varied between 10?4 and 10?9 M. The concentrations that inhibited AChE were calculated between 1.15 and 3.45 μM in seven compounds (4a, 4b, 4h, 4l, 4m, 4q, 4r). Compounds 4m, 4b, and 4l represented 1.15, 1.31, 1.34 μM (IC50) inhibitions, respectively. Although the inhibition values are lower than that of donepezil, they are considerable. Modeling studies of these analogs revealed similar positioning with donepezil, in which Ar–Ar interactions with Tyr337 and Trp 286 exist.
Sahin, Zafer,Biltekin, Sevde Nur,Bülbül, Emre Fatih,Yurttas, Leyla,Berk, Barkin,Demirayak, ?eref
p. 283 - 293
(2020/10/29)

Synthesis and Structure-Activity Relationship of Dual-Stage Antimalarial Pyrazolo[3,4- b]pyridines
Malaria remains one of the most deadly infectious diseases, causing hundreds of thousands of deaths each year, primarily in young children and pregnant mothers. Here, we report the discovery and derivatization of a series of pyrazolo[3,4-b]pyridines targeting Plasmodium falciparum, the deadliest species of the malaria parasite. Hit compounds in this series display sub-micromolar in vitro activity against the intraerythrocytic stage of the parasite as well as little to no toxicity against the human fibroblast BJ and liver HepG2 cell lines. In addition, our hit compounds show good activity against the liver stage of the parasite but little activity against the gametocyte stage. Parasitological profiles, including rate of killing, docking, and molecular dynamics studies, suggest that our compounds may target the Qo binding site of cytochrome bc1.
Eagon, Scott,Hammill, Jared T.,Sigal, Martina,Ahn, Kevin J.,Tryhorn, Julia E.,Koch, Grant,Belanger, Briana,Chaplan, Cory A.,Loop, Lauren,Kashtanova, Anna S.,Yniguez, Kenya,Lazaro, Horacio,Wilkinson, Steven P.,Rice, Amy L.,Falade, Mofolusho O.,Takahashi, Rei,Kim, Katie,Cheung, Ashley,Dibernardo, Celine,Kimball, Joshua J.,Winzeler, Elizabeth A.,Eribez, Korina,Mittal, Nimisha,Gamo, Francisco-Javier,Crespo, Benigno,Churchyard, Alisje,García-Barbazán, Irene,Baum, Jake,Anderson, Marc O.,Laleu, Beno?t,Guy, R. Kiplin
p. 11902 - 11919
(2020/11/26)

Discovery of novel potent GPR40 agonists containing imidazo[1,2-a]pyridine core as antidiabetic agents
Free fatty acid receptor 1 (FFA1 or GPR40) has been studied for many years as a target for the treatment of type 2 diabetes mellitus. In order to increase potency and reduce hepatotoxicity, a series of novel compounds containing imidazo[1,2-a]pyridine sca
Ye, Zhiwen,Liu, Chunxia,Zou, Feng,Cai, Yan,Chen, Bin,Zou, Yuxing,Mo, Jiaxian,Han, Ting,Huang, Wenlong,Qiu, Qianqian,Qian, Hai
(2020/06/19)

Facile Synthesis of α-Haloketones by Aerobic Oxidation of Olefins Using KX as Nonhazardous Halogen Source
An operationally simple and safe synthesis of α-haloketones using KBr and KCl as nonhazardous halogen sources is reported. It involves an iron-catalysed reaction of alkenes with KBr/KCl using O2 as terminal oxidant under the irradiation of visible-light. This strategy avoids the risks associated with handling halo-contained electrophiles (Cl2, Br2, NCS, NBS). The process is tolerant to several functional groups, and extended to a range of substituted styrenes in up to 89% yield. A radical reaction pathway is proposed based on control experiments and spectroscopy studies.
Luo, Zhibin,Meng, Yunge,Gong, Xinchi,Wu, Jie,Zhang, Yulan,Ye, Long-Wu,Zhu, Chunyin
supporting information
p. 173 - 177
(2020/01/02)

A focused structure-activity relationship study of psoralen-based immunoproteasome inhibitors
The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. The development of immunoproteasome-selective inhibitors with non-peptidic scaffolds remains a challenging task. Here, we describe a focused series of psoralen-based inhibitors of the β5i subunit of the immunoproteasome with different substituents placed at position 4′. The most promising compound was further evaluated through changes at position 3 of the psoralen ring. Despite a small decrease in the inhibitory potency in comparison with the parent compound, we were able to improve the selectivity against other subunits of both the immunoproteasome and the constitutive proteasome. The most potent compounds discriminated between both proteasome types in cell lysates and also showed a decrease in cytokine secretion in peripheral blood mononuclear cells.
?terman, Andrej,Gobec, Martina,Gobec, Stanislav,Mravljak, Janez,Ra??an, Irena Mlinari?,Schiffrer, Eva Shannon,Sosi?, Izidor
supporting information
p. 1958 - 1965
(2019/11/20)

Diaryl-containing imidazole compound and preparation method and medical application thereof
The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).
-
Paragraph 0174; 0175; 0176

(2019/02/21)

A visible-light-induced cascade reaction of etherification/C-C cyclization: Efficient synthesis of dibenzo[: B, d] oxepin-7(6 H)-ones
A visible-light-induced palladium-catalyzed cascade reaction was developed by etherification/C-C coupling cyclization of α-bromoacetophenones with phenols. A series of dibenzo[b,d]oxepin-7(6H)-one derivatives were efficiently synthesized by using this method in good yields. Furthermore, this method was applied to the synthesis of protosappanin A. The protocol has advantages such as simple reaction conditions, wide range of substrates and high reaction efficiency.
Fu, Wanyong,Yu, Aixia,Jiang, Hongshuo,Zuo, Minghui,Wu, Hongfeng,Yang, Zhongwen,An, Qi,Sun, Zhizhong,Chu, Wenyi
supporting information
p. 3324 - 3327
(2019/04/03)

Vinylethylene Carbonates as α,β-Unsaturated Aldehyde Surrogates for Regioselective [3 + 3] Cycloaddition
Herein, we report a novel stepwise addition-controlled ring size method, to access tetrahydropyrimidines through an operationally simple [3 + 3] cycloaddition of vinylethylene carbonates with triazinanes. Interestingly, we could also use this method for a [3 + 3] oxidative cycloaddition, which allows the facile synthesis of polysubstituted terphenyls under mild conditions. Mechanistic studies suggest that vinylethylene carbonates could generate α,β-unsaturated aldehydes as 3-carbon synthons for cycloaddition via a combination process of Pd-catalyzed decarboxylation and β-H elimination.
Xu, Yi,Chen, Lu,Yang, Yu-Wen,Zhang, Zhiqiang,Yang, Weibo
supporting information
p. 6674 - 6678
(2019/09/03)

Novel thiazole-piperazine derivatives as potential cholinesterase inhibitors
Dementia is a cognitive disorder mostly associated with Alzheimer's disease (AD) in addition to being seen in many other diseases of the central nervous system (CNS). The limited number of drugs is not sufficient to provide adequate improvement to increase the quality of life of patients suffering from this symptom; therefore, all treatment options should be evaluated in detail. In this study, new molecules, [2-(4-(2/3/4-substituted phenyl)piperazin-1-yl)-4-phenylthiazol-5-yl][3/4-substituted phenyl]methanone derivatives (1-44), were obtained and analyzed in terms of their anticholinesterase activities. Kinetic mode and molecular interactions were also evaluated. An enzyme inhibition study was undertaken on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the Ellman method. Maestro program was used in molecular modeling studies. Forty-four compounds were evaluated on AChE and BChE enzymes at 10?3 and 10?4 concentrations. The inhibition concentrations were calculated as 0.268μM to 2.104μM for six compounds (4, 5, 16, 27, 37, and 38) on AChE. Compound 5 including the 4-methoxy substituent (IC50: 0.268μM) and compound 38 containing the 4-methoxy and 3-methyl substituents (IC50: 0.286μM) showed the highest AChE inhibitory activity. They were further examined in terms of hydrogen bonding with Arg296 and Ar-Ar interaction with Trp286. The activity of compound 5 was also assessed in mixed-type kinetic mode.
Demirayak, ?eref,?ahin, Zafer,Erta?, Merve,Bülbül, Emre Fatih,Bender, Ceysu,Biltekin, Sevde Nur,Berk, Barkin,Sa?l?k, Begüm Nurpelin,Levent, Serkan,Yurtta?, Leyla
p. 3370 - 3386
(2019/11/03)

Method of utilizing micro channel reactor to prepare pentafluorophenoxyl ketones continuously
The invention discloses a method of utilizing a micro channel reactor to prepare pentafluorophenoxyl ketones continuously. Cheap and easily available styrene and pentafluorophenol are taken as the primary raw materials, two step continuous reactions are carried out in a micro channel reactor to obtain pentafluorophenoxyl ketones, the reaction time is shortened to several minutes from several hours; the product yield is high, the reaction efficiency is obviously enhanced, no any pricy organic catalyst or metal catalyst is needed, the operation is simple, the cost is low, the preparation technology is easy to control, the safety is high, the reaction conditions are mild, and the method can be applied to industrial production.
-
Paragraph 0052-0053

(2019/06/30)

Synthesis of (Z)-nitroalkene derivatives through oxidative dehydrogenation coupling of α-aminocarbonyl compounds with nitromethane by copper catalysis
A novel copper-catalyzed cross-dehydrogenative coupling reaction of α-amino carbonyl compounds with nitromethane to synthesis of (Z)-nitroalkene derivatives has been established. (Z)-Nitroalkene derivatives are achieved through the cleavage of sp3 CsbndH bonds and formation of CsbndC double bond, with mild reaction conditions and excellent stereoselectivity.
Zhu, Menghua,Chen, De,Zeng, Sheng,Xing, Chenhu,Deng, Wei,Xiang, Jiannan,Wang, Rui-Jia
supporting information
p. 3214 - 3219
(2018/07/21)

Divergent synthesis of N-heterocycles by Pd-catalyzed controllable cyclization of vinylethylene carbonates
Here, we report a palladium-catalyzed controllable cyclization of vinyl ethylene carbonates that proceeds through formal migration [2+3] and [5+2] cycloadditions, respectively, under mild conditions. The transformation described here affords a series of synthetically versatile 5,7-membered N-heterocycles which are found in natural products and pharmaceuticals with biological and medicinal properties.
Yang, Yuwen,Yang, Weibo
supporting information
p. 12182 - 12185
(2018/11/21)

Diversity-Orientated Stereoselective Synthesis through Pd-Catalyzed Switchable Decarboxylative C?N/C?S Bond Formation in Allylic Surrogates
Switchable catalytic transformation of reactants can be a powerful approach towards diversity-orientated synthesis from easily available molecular synthons. Herein, an endogenous ligand-controlled, Pd-catalyzed allylic substitution allowing for either selective C?N or C?S bond formation using vinylethylene carbonates (VECs) and N-sulfonylhydrazones as coupling partners has been developed. This versatile methodology provides a facile, divergent route for the highly chemo- and stereoselective synthesis of functional allylic sulfones or sulfonohydrazides. The newly developed protocol features wide substrate scope (nearly 80 examples), broad functional group tolerance, and potential for the late-stage functionalization of bioactive compounds. The isolation and crystallographic analysis of a catalytically competent π-allyl Pd complex suggests that the pathway leading to the allylic products proceeds through a different manifold as previously proposed for the functionalization of VECs with nucleophiles.
Deng, Lei,Kleij, Arjan W.,Yang, Weibo
supporting information
p. 19156 - 19161
(2018/11/30)

Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors
(Table presented.). After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid-20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. However, these drugs have limited use in advanced AD and dementia. Recently, the anticholinesterase activity of various heterocyclic-framed compounds, including piperazine derivatives, has been investigated, and compounds with similar effects to known drugs have been identified. The aim of this study was to design new donepezil analogs. In this study, 66 original piperazinyl thiazole derivatives were synthesized by the reaction of piperazine N′-benzoyl thioamides and bromoacetophenones to inhibit AChE. Biological activity was measured by the Ellman method. Compounds 35, 38, 40, 45, 57, and 61 showed a high inhibitory effect among the series (80.36%–83.94% inhibition), and donepezil had a 96.42% inhibitory effect. The IC50 values of compounds 35, 38, and 40, were calculated as 0.9767 μM, 0.9493 μM, and 0.8023 μM, respectively. Compound 45 (IC50 = 1.122), Compound 57 (IC50 = 1.2130) and 61 (IC50 = 0.9193) also exhibited good activity on AChE. Molecular modeling studies were in agreement with the predictions. Trp286, Arg296, and Tyr341 were the key amino acids at the active site. Both donepezil and synthesized compounds seemed to interact with these residues.
Sahin, Zafer,Ertas, Merve,Bender, Ceysu,Bülbül, Emre F.,Berk, Barkin,Biltekin, Sevde N.,Yurtta?, Leyla,Demirayak, ?eref
p. 406 - 425
(2018/10/26)

Water-controlled selective preparation of α-mono or α,α′-dihalo ketones: Via catalytic cascade reaction of unactivated alkynes with 1,3-dihalo-5,5-dimethylhydantoin
The control of a reaction that can produce multiple products from the same starting material is a highly attractive and challenging concept in organic synthesis. An efficient protocol for the selective synthesis of α-mono or α,α′-dihalo ketones via a water-controlled three-component thiourea-catalyzed cascade reaction of unactivated alkynes, 1,3-dihalo-5,5-dimethylhydantoin and water has been developed. α-Monohaloketones were obtained in aqueous acetone at 45 °C; conversely, α,α′-dihalo ketones were formed with pure water as the sole solvent at room temperature.
Wu, Chao,Xin, Xiu,Fu, Zhi-Min,Xie, Long-Yong,Liu, Kai-Jian,Wang, Zheng,Li, Wenyi,Yuan, Zhi-Hui,He, Wei-Min
p. 1983 - 1989
(2017/06/09)

Rh/DuanPhos-Catalyzed Asymmetric Hydrogenation of β-Acetylamino Vinylsulfides: An Approach to Chiral β-Acetylamino Sulfides
Rh/DuanPhos-catalyzed asymmetric hydrogenation of challenging β-acetylamino vinylsulfides has been developed, affording chiral β-acetylamino sulfides with high yields and excellent ee's (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral β-acetylamino sulfides. The potential utility of this protocol in the synthesis of Apremilast has also been disclosed.
Gao, Wenchao,Lv, Hui,Zhang, Xumu
supporting information
p. 2877 - 2880
(2017/06/07)

Copper-catalyzed oxidative cross-coupling of α-aminocarbonyl compounds with primary amines toward 2-oxo-acetamidines
A general and mild method for the construction of a carbon-nitrogen bond via copper-catalyzed oxidative cross-coupling of amines with α-aminocarbonyl compounds was achieved. Amines, either aliphatic primary amines, aromatic primary amines or secondary amines can be used as the starting materials. When R2 was different from R3, two isomers would be observed. Therefore, this reaction system has a broad substrate scope and provides a facile pathway for the synthesis of 2-oxo-acetamidines.
Chen, Chuang,Zhu, Menghua,Jiang, Lihui,Zeng, Zebing,Yi, Niannian,Xiang, Jiannan
p. 8134 - 8139
(2017/10/10)

Catalytic dehydrogenative dual functionalization of ethers: Dealkylation-oxidation-bromination accompanied by C-O bond cleavage: Via aerobic oxidation of bromide
Catalytic dehydrogenative dual functionalization (DDF) of ethers via oxidation, dealkylation, and α-bromination by the aerobic oxidation of bromide was developed to obtain the corresponding α-bromo ketones in high yields. In particular, the reaction of substituted tetrahydrofurans as cyclic ethers provided 3,3-dibromo tetrahydrofuran-2-ols in high yields selectively through the double α-bromination.
Moriyama, Katsuhiko,Hamada, Tsukasa,Nakamura, Yu,Togo, Hideo
supporting information
p. 6565 - 6568
(2017/07/10)

1,3-Dibromo-5,5-dimethylhydantoin mediated oxidative amidation of terminal alkenes in water
A variety of terminal alkenes were converted to the corresponding amides in yields of 25 to 86% in water via treatment with 1,3-dibromo-5,5-dimethylhydantoin, followed by reaction with molecular iodine and aq. NH3 (or amine) in one pot. This metal- and organic solvent-free protocol is not only suitable for styrene derivatives, but also, for the first time, works well on terminal aliphatic alkenes.
Ma, Chunhua,Fan, Guojie,Wu, Ping,Li, Zhi,Zhou, Yang,Ding, Qingjie,Zhang, Wei
p. 9889 - 9894
(2017/12/12)

TsNBr2mediated oxidative functionalization of alkynes
A new approach has been developed for oxidative transformation of alkynes by controlled manipulation of TsNBr2mediated process. Alkynes could be readily converted to ketones and α-bromoketones via an oxybromination–debromination sequence. When alkynes are treated successively with TsNBr2, KI and Na2SO3in a mixture of acetone and water at room temperature, corresponding ketones were obtained. On the other hand, treatment of alkynes with TsNBr2and Na2SO3in a mixture of ethyl acetate, acetone and water at room temperature could produce corresponding α-bromoketones. 1-Bromoalkynes could also be synthesized from corresponding alkynes within a very short time using TsNBr2at room temperature. In all cases, excellent yields of corresponding products are obtained.
Rajbongshi, Kamal Krishna,Hazarika, Debojit,Phukan, Prodeep
p. 4151 - 4158
(2016/07/06)

First Catalyzed Hydration of Haloalkynes by a Recyclable Catalytic System
The hydration of haloalkynes to give α-halomethyl ketones was achieved based on a combination of a Cu(OAc)2 catalyst and a TFA (trifluoroacetic acid) promoter. This is the first synthesis of chloro/bromo/iodo methyl ketones through a hydration reaction catalyzed by a recyclable catalytic system. The catalytic system has a wide substrate scope and excellent chemoselectivity, and the procedure can also be scaled up.
Zou, Huaxu,He, Weibao,Dong, Qizhi,Wang, Ruijia,Yi, Niannian,Jiang, Jun,Pen, Dongming,He, Weimin
p. 116 - 121
(2016/01/26)

Metal-free hydration of aromatic haloalkynes to α-halomethyl ketones
A highly regioselective and efficient metal-free hydration of aromatic haloalkynes to α-halomethyl ketones using cheap tetrafluoroboric acid as catalyst is described. The protocol is conducted under convenient conditions and affords products in good to excellent yields, with broad substrate scope, including a variety of aromatic alkynyl chlorides, alkynyl bromides, and alkynyl iodides.
Ye, Min,Wen, Yuelu,Li, Huifang,Fu, Yejuan,Wang, Qinghao
supporting information
p. 4983 - 4986
(2016/10/21)

In(OTf)3/acid co-catalyzed hydration of 1-haloalkynes to α-halomethyl ketones
A novel and efficient In(OTf)3and HOAc cooperatively catalyzed hydration of 1-haloalkynes is described. This method provides ready access to α-chloromethyl ketones, α-bromomethyl ketones and α-iodomethyl ketones in moderate to high yields from simple, inexpensive starting materials. A broad substrate scope is achieved, and the reaction is compatible with various functional groups, including alkoxy, trifluoromethyl, halide, hydroxyl, cyclohexyl, and heterocyclic groups.
Zeng, Ming,Huang, Rui-Xue,Li, Wen-Yi,Liu, Xiao-Wen,He, Fu-Ling,Zhang, Yi-Yuan,Xiao, Fang
p. 3818 - 3822
(2016/07/06)

Highly Efficient Synthesis of α-Halomethylketones via Ce(SO4)2/Acid Co-Catalyzed Hydration of Alkynes
A general atom-economical approach for the synthesis of α-halomethyl ketones is demonstrated through Ce(SO4)2/acid co-catalyzed hydration of a wide range of haloalkynes. The reactions are conducted under convenient conditions and provide products with excellent regioselectivity in good to excellent yields, with broad substrate scope. This protocol is an alternative to conventional α-halogenation of ketones.
Zou, Huaxu,Jiang, Jun,Yi, Niannian,Fu, Wenqiang,Deng, Wei,Xiang, Jiannan
supporting information
p. 1251 - 1254
(2016/12/27)

Total synthesis of protosappanin A and its derivatives via palladium catalyzed ortho C-H activation/C-C cyclization under microwave irradiation
A total synthesis method for protosappanin A, which is a complex natural product with many biological activities, was developed with 6 linear steps. Dibenzo[b,d]oxepinones as the key intermediates of the synthetic route were prepared by a palladium-catalyzed ortho C-H activation/C-C cyclization under microwave irradiation. 25 derivatives of protosappanin A were obtained.
Liu, Jiaqi,Zhou, Xuan,Wang, Chenglong,Fu, Wanyong,Chu, Wenyi,Sun, Zhizhong
supporting information
p. 5152 - 5155
(2016/05/02)

Synthesis and antimicrobial activity evaluation of new dithiocarbamate derivatives bearing thiazole/benzothiazole rings
The synthesis of 2-(substituted phenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A1-A24) derivatives and 2-(4-substituted thiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B1-B14) derivatives was undertaken starting from the potassium salt of 4-(2-pyrimidinyl)piperazine dithiocarbamate. The structures of the obtained compounds were elucidated by1H NMR,13C NMR, MS spectral data, and elemental analysis. The antimicrobial activity of the thirty eight newly synthesized compounds were tested against 12 microorganism strains using the microdilution technique. Compounds 2-(4-ethoxycarbonylthiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B12), 2-(3-fluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A18) and 2-(3,4-difluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A21) were determined to possess high antimicrobial activity.
Yurtta?, Leyla,?zkay, Yusuf,Duran, Murat,Turan-Zitouni, Gülhan,?zdemir, Ahmet,Cantürk, Zerrin,Kü?üko?lu, Kaan,Kaplanc?kl?, Zafer As?m
p. 1166 - 1173
(2016/07/27)

1,3-Dibromo-5,5-dimethylhydantoin (DBH) mediated one-pot syntheses of α-bromo/amino ketones from alkenes in water
α-Bromo ketones are versatile intermediates of high practical utility. Traditional approaches to these compounds are restricted to a relatively hazardous/complex reagent combination, a long reaction time, the use of non-environmentally friendly solvents, or a limited substrate scope. Herein, we describe the development of a new methodology for the preparation of α-bromo ketones from alkenes using 1,3-dibromo-5,5-dimethylhydantoin (DBH) as a bromine source and an oxidant simultaneously. This easy to carry out two-step one-pot protocol proceeds in water and provides high yield of a great variety of α-bromo ketones. Addition of an amine to the intermediate α-bromo ketone further enables the preparation of α-amino ketones in a one-pot sequence.
Xu, Senhan,Wu, Ping,Zhang, Wei
p. 11389 - 11395
(2016/12/18)

Synthesis and structure-activity relationship of aminoarylthiazole derivatives as correctors of the chloride transport defect in cystic fibrosis
Abstract The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel present in the membrane of epithelial cells. Mutations affecting the CFTR gene cause cystic fibrosis (CF), a multi-organ severe disease. The most common CF mutation, F508del, impairs the processing and activity (gating) of CFTR protein. Other mutations, like G551D, only cause a gating defect. Processing and gating defects can be targeted by small molecules called generically correctors and potentiators, respectively. Aminoarylthiazoles (AATs) represent an interesting class of compounds that includes molecules with dual activity, as correctors and potentiators. With the aim to improve the activity profile of AATs, we have now designed and synthesized a library of novel compounds in order to establish an initial SAR that may provide indications about the chemical groups that are beneficial or detrimental for rescue activity. The new compounds were tested as correctors and potentiators in CFBE41o-expressing F508del-CFTR using a functional assay. A dual active compound, AAT-4a, characterized by improved efficacy and marked synergy when combined with the corrector VX-809 has been identified. Moreover, by computational methods, a possible binding site for AATs in nucleotide binding domain NBD1 has been detected. These results will direct the synthesis of new analogues with possibly improved activity.
Pesce, Emanuela,Bellotti, Marta,Liessi, Nara,Guariento, Sara,Damonte, Gianluca,Cichero, Elena,Galatini, Andrea,Salis, Annalisa,Gianotti, Ambra,Pedemonte, Nicoletta,Zegarra-Moran, Olga,Fossa, Paola,Galietta, Luis J.V.,Millo, Enrico
supporting information
p. 14 - 35
(2015/06/08)

Synthesis and biological evaluation of N-(4-phenylthiazol-2-yl)cinnamamide derivatives as novel potential anti-tumor agents
In this study, a series of novel N-(4-phenylthiazol-2-yl)cinnamamide derivatives (7a-8n) were synthesized and evaluated for their anti-proliferative activities in vitro by MTT assay and a possible antitumor mechanism was also explored. SAR analysis showed that steric effects played an important role on the anti-tumor activity. The most potent analogue 8f showed excellent inhibitions on the K562, Bel7402, A549 and Jurkat cells ranging from sub-micromolar to nanomolar concentration. Compound 8f inhibited Jurkat cells with an IC50 value of 0.035 μM with no apparent toxicity in different non-cancerous cells. Furthermore, it was suggested that the possible mechanism of 8f might be associated with inducing cancer cell apoptosis following flow cytometer analysis and Hoechst 33358 staining assays.
Luo, Yong,Zhu, Yongxia,Ran, Kai,Liu, Zhihao,Wang, Ningyu,Feng, Qiang,Zeng, Jun,Zhang, Lidan,He, Bing,Ye, Tinghong,Zhu, Shirui,Qiu, Xiaolong,Yu, Luoting
supporting information
p. 1036 - 1042
(2015/06/25)

Design, Synthesis and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel DPP-4 Inhibitors
A new series of DPP-4 inhibitors with imidazo[1,2-a]pyridine scaffold were designed by exploiting scaffold hopping strategy and docking study. Based on docking binding model, structural modifications of 2-benzene ring and pyridine moieties of compound 5a led to the identification of compound 5d with 2, 4-dichlorophenyl group at the 2-position as a potent (IC50 = 0.13 μm), selective (DPP-8/DPP-4 = 215 and DPP-9/DPP-4 = 192) and in vivo efficacious DPP-4 inhibitor. Further, molecular docking revealed that compound 5d could retain key binding features of DPP-4 with the pyridine moiety of imidazo[1,2-a]pyridine ring providing an additional π-π interaction with Phe357 of DPP-4. Compound 5d might be a promising lead for further development of novel DPP-4 inhibitor treating T2DM.
Li, Qing,Zhou, Muxing,Han, Li,Cao, Qing,Wang, Xinning,Zhao, Leilei,Zhou, Jinpei,Zhang, Huibin
p. 849 - 856
(2015/10/06)

Metal-free protocol for the synthesis of α-bromo ketones from olefins using TsNBr2
TsNBr2 reacts readily with olefins to produce α-bromo ketones at room temperature. The synthesis was carried out by treating an olefin with TsNBr2 in acetone-water mixture in 30:1 ratio. Excellent yield of corresponding α-bromo ketone could be achieved within a short time.
Rajbongshi, Kamal Krishna,Hazarika, Debojit,Phukan, Prodeep
supporting information
p. 356 - 358
(2015/04/27)

Silica gel catalyzed α-bromination of ketones using N-bromosuccinimide: An easy and rapid method
An easy and rapid method for the α-bromination of ketones using N-bromosuccinimide (NBS) catalyzed by silica gel in methanol under reflux conditions was developed. The expected products were formed in excellent isolated yields within a short period of time (5-20 min). Major advantages of the present procedure include use of inexpensive and readily available catalyst, exclusion of pre- and post-chemical treatment of catalyst and use of methanol as solvent instead of ethers and chlorinated solvents.
Mohan Reddy, Bodireddy,Venkata Ramana Kumar, Velpula,Chinna Gangi Reddy, Nallagondu,Mahender Rao, Siripragada
p. 179 - 182
(2014/02/14)

AgF/TFA-promoted highly efficient synthesis of α-haloketones from haloalkynes
A AgF/TFA-promoted highly efficient synthesis of a wide range of α-haloketones from haloalkynes is described. The reactions are conducted under convenient conditions and provide products in moderate to excellent yields, with broad substrate scope, including a variety of aromatic chloroalkynes and bromoalkynes.
Chen, Zheng-Wang,Ye, Dong-Nai,Ye, Min,Zhou, Zhong-Gao,Li, Shen-Huan,Liu, Liang-Xian
supporting information
p. 1373 - 1375
(2014/03/21)

Efficient synthetic approach to substituted benzo[b]furans and benzo[b]thiophenes by iodine-promoted cyclization of enaminones
An efficient synthetic approach to the substituted benzo[b]furan and benzo[b]thiophene scaffolds by iodine-mediated cyclization of the corresponding enaminones is described. This protocol was applied to a large series of these latter precursors to afford the respective benzoheterocycles substituted at the C-2 position by a carbonyl group functionality. A study of the factors that control this process reveals that the reactivity depends on the presence of electron-donor groups in the aryl ring of the aryloxycarbonylic and arylthiocarbonylic moieties.
Labarrios, Ehecatl,Jerezano, Alberto,Jimenez, Fabiola,Del Carmen Cruz, Maria,Delgado, Francisco,Zepeda, L. Gerardo,Tamariz, Joaquin
p. 954 - 971
(2014/08/05)

Gold-catalyzed hydration of haloalkynes to α-halomethyl ketones
A general atom-economical approach for the synthesis of α-halomethyl ketones is demonstrated through hydration of a wide range of haloalkynes. Other outstanding features include excellent yields from both alkyl- and aryl-substituted haloalkynes and wide functional group tolerance. This protocol is an alternative to conventional α-halogenation of ketones.
Xie, Longyong,Wu, Yundong,Yi, Weiguo,Zhu, Lei,Xiang, Jiannan,He, Weimin
p. 9190 - 9195
(2013/10/08)

NOVEL COMPOUNDS
This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3, R3a have meanings given in the description.
-
Paragraph 0188; 0189; 0190; 0191

(2013/06/27)

4-ARYL IMIDAZOLE DERIVATIVES AS MGLUR5 POSITIVE ALLOSTERIC MODULATORS
This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
-
Page/Page column 29

(2013/07/05)

NOVEL COMPOUNDS
This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3, R3a have meanings given in the description.
-
Page/Page column 30

(2013/07/05)

NOVEL COMPOUNDS
This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
-
Paragraph 0157; 0158; 0159; 0160

(2013/06/27)

Regioselective α-bromination of aralkyl ketones using n-bromosuccinimide in the presence of montmorillonite K-10 clay: A simple and efficient method
A simple and more convenient method has been developed for regioselective α-bromination of various aralkyl ketones with N-bromosuccinimide (NBS) in the presence of Montmorillonite K-10 catalyst in methanol at 60-65 °C. The present procedure offers advantages of short reaction time, simple workup, good yields of products and reusability of the catalyst for four times without loss of activity. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
Mohan, Reddy Bodireddy,Reddy, N. C. Gangi
p. 2603 - 2614
(2013/07/26)

3,8-DIAZA-BICYCLO[4.2.0]OCT-3-YL AMIDES
The present invention relates to 3,8-diaza-bicyclo[4.2.0]oct-3-yl amide derivatives of formula (I), wherein the relative configuration of the diazabicyclooctane moiety is cis; and wherein Ar1, and Ar2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.
-
Page/Page column 74; 75

(2012/07/13)

3,8-DIAZA-BICYCLO[4.2.0]OCT-8-YL AMIDES
The present invention relates to 3,8-diaza-bicyclo[4.2.0]oct-8-yl amide derivatives of formula (I) Formula (I) wherein the relative configuration of the diazabicyclooctane moiety is cis; and wherein Ar1, and Ar 2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.
-
Page/Page column 66

(2012/07/13)

Oxidative bromination of ketones using ammonium bromide and oxone
A highly efficient, environmentally safe and economic method for selective α-monobromination of aralkyl, cyclic, acyclic, 1,3-diketones and β-keto esters and α,α-dibromination of 1,3-diketones and β-keto esters without catalyst is reported using ammonium bromide as a bromine source and oxone as an oxidant. The reaction proceeds at ambient temperature and yields range from moderate to excellent. Bromination of unsymmetrical ketones takes place at the less substituted α-position predominantly. Aromatisation of tetralones is also carried out with this reagent system.
MacHarla, Arun Kumar,Chozhiyath Nappunni, Rohitha,Marri, Mahender Reddy,Peraka, Swamy,Nama, Narender
supporting information; experimental part
p. 191 - 195
(2012/01/17)