- Anomalous Rate of Bromination of a Ketone: First-order Dependence on Bromine Concentration
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The rate of acid-catalysed bromination of 2,4,6-trimethylacetophenone in 50percent aqueous acetic acid is first-order in bromine, in contrast with acetophenone and other reported ketones at comparable concentrations.
- Pinkus, A. George,Gopalan, Raghavachary
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- One-Pot Preparation of Aromatic Amides, 4-Arylthiazoles, and 4-Arylimidazoles from Arenes
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Simple treatment of arenes with α-bromoacetyl chloride and AlCl3, followed by the reaction with molecular iodine and aq. NH3, thioamides, or amidines gave the corresponding primary aromatic amides, 4-arylthiazoles, or 4-arylimidazoles in good yields, respectively. Aryl α-bromomethyl ketones are the key intermediates in those reactions. Primary aromatic amides were formed from arenes through the reaction of aryl α-bromomethyl ketones with molecular iodine and aq. NH3, and 4-arylthiazoles and 4-arylimidazoles were formed from arenes through the reactions of aryl α-bromomethyl ketones with thioamides and amidines, respectively, in one pot under transition-metal-free conditions.
- Yamamoto, Takahiro,Togo, Hideo
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p. 4187 - 4196
(2018/08/21)
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- Indolizine–Squaraines: NIR Fluorescent Materials with Molecularly Engineered Stokes Shifts
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The development of deep red and near infrared emissive materials with high quantum yields is an important challenge. Several classes of squaraine dyes have demonstrated high quantum yields, but require significantly red-shifted absorptions to access the N
- McNamara, Louis E.,Rill, Tana A.,Huckaba, Aron J.,Ganeshraj, Vigneshraja,Gayton, Jacqueline,Nelson, Rachael A.,Sharpe, Emily Anne,Dass, Amala,Hammer, Nathan I.,Delcamp, Jared H.
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supporting information
p. 12494 - 12501
(2017/09/18)
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- Identification of novel 2-aminothiazole conjugated nitrofuran as antitubercular and antibacterial agents
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The emergence of antibiotic resistant pathogens is an ongoing main problem in the therapy of bacterial infections. In order to develop promising antitubercular and antibacterial lead compounds, we designed and synthesized a new series of derivatives of 2-aminothiazole conjugated nitrofuran with activities against both Mycobacterium tuberculosis and Staphylococcus aureus. Eight compounds 12e, 12k, 12l, 12m, 18a, 18d, 18e, and 18j emerged as promising antitubercular agents. Structure–activity relationships (SARs) were discussed and showed that the derivatives substituted at the position-3 of benzene of 5-nitro-N-(4-phenylthiazol-2-yl)furan-2-carboxamide exhibited superior potency. The most potent compound 18e, substituted with benzamide at this position, displayed minimum inhibitory concentrations (MICs) of 0.27 μg/mL against Mtb H37Ra and 1.36 μg/mL against S. aureus. Furthermore, compound 18e had no obvious cytotoxicity to normal Vero cells (IC50= 50.2 μM). The results suggest that the novel scaffolds of aminothiazole conjugated nitrofuran would be a promising class of potent antitubercular and antimicrobial agents.
- Ran, Kai,Gao, Chao,Deng, Hongxia,Lei, Qian,You, Xinyu,Wang, Ningyu,Shi, Yaojie,Liu, Zhihao,Wei, Wei,Peng, Cuiting,Xiong, Lu,Xiao, Kunjie,Yu, Luoting
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supporting information
p. 3669 - 3674
(2016/07/21)
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- Synthesis and biological evaluation of N-(4-phenylthiazol-2-yl)cinnamamide derivatives as novel potential anti-tumor agents
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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
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supporting information
p. 1036 - 1042
(2015/06/25)
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- Discovery of 4-aryl-N-arylcarbonyl-2-aminothiazoles as Hec1/Nek2 inhibitors. Part I: Optimization of in vitro potencies and pharmacokinetic properties
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A series of 4-aryl-N-arylcarbonyl-2-aminothiazoles of scaffold 4 was designed and synthesized as Hec1/Nek2 inhibitors. Structural optimization of 4 led to compound 32 bearing C-4′ 4-methoxyphenoxy and 4-(o-fluoropyridyl) carbonyl groups that showed low nanomolar in vitro antiproliferative activity (IC50: 16.3-42.7 nM), high intravenous AUC (64.9 μM·h, 2.0 mg/kg) in SD rats, and significant in vivo antitumor activity (T/C = 32%, 20 mg/kg, IV) in mice bearing human MDA-MB-231 xenografts. Cell responses resulting from Hec1/Nek2 inhibition were observed in cells treated with 32, including a reduced level of Hec1 coimmunoprecipitated with Nek2, degradation of Nek2, mitotic abnormalities, and apoptosis. Compound 32 showed selectivity toward cancer cells over normal phenotype cells and was inactive in a [ 3H]astemizole competitive binding assay for hERG liability screening. Therefore, 32 is as a good lead toward the discovery of a preclinical candidate targeting Hec1/Nek2 interaction.
- Lee, Ying-Shuan E.,Chuang, Shih-Hsien,Huang, Lynn Y. L.,Lai, Chun-Liang,Lin, Yu-Hsiang,Yang, Ju-Ying,Liu, Chia-Wei,Yang, Sheng-Chuan,Lin, Her-Sheng,Chang, Chia-Chi,Lai, Jun-Yu,Jian, Pei-Shiou,Lam, King,Chang, Jia-Ming,Lau, Johnson Y. N.,Huang, Jiann-Jyh
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p. 4098 - 4110
(2014/06/09)
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- IMPROVED MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR
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Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Such compounds disrupt Nek2/Hec1 binding and may be useful as chemotherapeutic agents for neoplastic diseases
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Paragraph 00263
(2013/06/27)
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- Temperature dependent product distribution in photolysis of o-alkylphenacyl benzoates
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Temperature effect on photochemical reactions of ortho-alkylphenacyl benzoates, one of the recently developed photoremovable protecting groups (PPG), giving indanones (IN) and benzocyclobutenols (CB) was examined. As temperature was lowered, CB was formed preferentially over IN and the amount of IN increased as temperature was elevated. Arrhenius plot of ln(IN/CB) versus 1/T gave a straight line from which EaIN-EaCB and A IN/ACB were obtained. The least sterically hindered 2-methylphenacyl benzoate (1) gave the highest EaIN-EaCB and AIN/ACB among the ortho-alkylphenacyl benzoates tested in this research including 2,4,6-trimethylphenacyl benzoate (2) and 2,4,6-triisopropylphenacyl benzoate (3).
- Jang, Mi,Lim, Bum Hee,Ryu, Hyuk Jun,Park, Bong Ser
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p. 7175 - 7179
(2013/12/04)
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- Modulators Of HEC1 Activity And Methods Therefor
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Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.
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Page/Page column 9
(2011/10/10)
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- α-Telluration of 2,4,6-trimethylacetophenone under mild conditions: Role of steric factor in the solid state structures of Te(II and IV) compounds
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Elemental tellurium inserts into the Csp3-Br bond of α-bromomesitylmethyl ketone and due to its strong carbophilic character affords the crystalline C-tellurated derivative of 2,4,6-trimethylacetophenone, (MesCOCH2)2TeBr2, 1b in over 80% yield. Electrophilic substitution of the parent ketone with aryltellurium trichlorides, at room temperature, gives nearly quantitative yields of unsymmetrical alkylaryltellurium dichlorides (MesCOCH2)ArTeCl2 (Ar = mesityl, Mes, 2a; 1-naphthyl, Np, 3a; anisyl, Ans, 4a). Fairly stable mesitoylmethyltellurium(II) derivatives, (MesCOCH2)2Te, 1 and (MesCOCH2)ArTe (Ar = Mes, 2; Np, 3 and Ans, 4) obtained as the reduction products of their dihalotellurium(IV) analogues, readily undergo oxidative addition of dihalogens to afford the corresponding (MesCOCH 2)2TeX2 (X = Cl, 1a; Br 1b; I, 1c) and (MesCOCH2)ArTeX2 (X = Cl, Br, I, Ar = Mes, 2a, 2b, 2c; Np, 3a, 3b, 3c and Ans, 4a, 4b, 4c). Crystallographic structural characterization of 1, 1b, 2, 2a, 2b, 2c, 3, 3a and 4c illustrates that the steric demand of mesityl group appreciably influences primary geometry around the 5-coordinate Te(IV) atom when it is bound directly to it. It also makes the Te atom inaccessible for the ubiquitous Te?X intermolecular secondary bonding interactions that result in supramolecular structures. In the crystal lattice of symmetrical telluroether 1, an interesting supramolecular synthon based upon reciprocatory weak C-H?O H-bonding interaction gives rise to chains via self-assembly. α-Bromo-2,4,6-trimethylacetophenone adds oxidatively to Te0/TeII to give the dialkyl- or alkylarylTeIV species which on reduction afford carbonyl-functionalized telluroethers.
- Chauhan, Ashok K.S.,Singh, Puspendra,Srivastava, Ramesh C.,Butcher, Ray J.,Duthie, Andrew
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scheme or table
p. 2118 - 2125
(2010/09/20)
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- 4-Aminothiazole derivatives, their preparation and their use as inhibitors of cyclin-dependent kinases
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This invention is directed to aminothiazole compounds of formula (I) wherein R1 is a substituted or unsubstituted group selected from : C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R1 is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol, thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; and R2 is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent to the point of attachment, which ring structure is optionally further substituted, where each substituent of R2 independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; or a pharmaceutically acceptable salt of a compound of formula (I), or a prodrug or pharmaceutically active metabolite of a compound of formula (I) or pharmaceutically acceptable salt thereof, for inhibiting cyclin-dependent kinases (CDKs), such as CDK1, CDK2, CDK4, and CDK6. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds and to methods of treating malignancies and other disorders by administering effective amounts of such compounds.
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Example C(57)
(2010/11/29)
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- Branched alkylamino derivatives of thiazole, processes for preparing them and pharmaceutical compositions containing them
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The invention relates to the derivatives of formula I: STR1 in which R1 represents a phenyl or naphthyl radical (optionally substituted), R2 represents a hydrogen or halogen atom or an alkyl, hydroxymethyl or formyl radical, R3
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- Rates and Equilibria of Keto-Enol and -Enolate Ion Interconversion in the 2,4,6-Trimethylacetophenone System. Reinvestigation of the Unusual Bromination Reaction
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The bromination of 2,4,6-trimethylacetophenone, whose unusual kinetics were once thought to be the result of slow, sterically hindered addition of bromine to the enol, was found to be a ring- rather than a side-chain-substitution reaction; kinetic and thermodynamic charactristics of this keto-enol system were determined by a combination of flash-photolytic and conventional kinetic techniques and were found to be little different from those of the parent (unsubstituted) acetophenone keto-enol system.
- Kresge, A. J.,Schepp, N. P.
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p. 1548 - 1549
(2007/10/02)
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- AUXILIARY SRTUCTURE AND ASYMMETRIC INDUCTION IN THE "MUKAIYAMA-ALDOL" REACTIONS OF CHIRAL SILYL KETENE ACETALS
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A variety of chiral auxiliaries R*OH were prepared and tested for levels of asymmetric induction control in the "Mukaiyama-aldol" reaction of chiral silyl ketene acetals.Structural features required for high levels of control are discussed.
- Gennari, Cesare,Molinari, Francesco,Cozzi, PierGiorgio,Oliva, Ambrogio
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p. 5163 - 5166
(2007/10/02)
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- Studies on the Mechanism of Acid-Catalyzed Bromination of a Hindered Alkyl Aryl Ketone: 2,4,6-trimethylacetophenone. Rate Dependence on Bromine Concentration
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According to the generally accepted Lapworth mechanism for halogenation of ketones, where the rate of reaction is independent of halogen concentration, the slow, rate-determining step is the formation of enol or enolate.The rate of reaction of bromine with 2,4,6-trimethylacetophenone (1) was found to depend on bromine concentration at moderately high concentrations.In the proposed mechanism, reaction of bromine with enol is rate determining - the enolization step being faster.A carbocation (4) instead of a bromonium ion is proposed as the intermediate from reaction of enol with bromine.Rates were determined by following the decrease in bromine concentration at 449 nm under these conditions: 50percent acetic acid (v/v), HBr catalysis, and ionic strength adjusted with sodium perchlorate at 25 deg C.With excess ketone, the average pseudo-first-order rate constant was 1.82x10-3 s-1.At a fixed bromine concentration and at varying equal concentrations of both ketone and bromine, k2 values were 4.34x10-2 and 4.39x10-2 L mol-1 s-1, respectively.In studies on the effect of bromide ion on the rate, molecular bromine was found to be the active brominating agent with Br3- contributing to only 0.6percent of the rate constant.Added chloride ion increased the rate; this was explained by Br2/Cl- interchange to form Br-Cl, a more effective brominating agent.Only bromo ketone was isolated in a preparative-scale reaction containing chloride ions.Added acetate ions decreased the rate as a result of a decrease in proton concentration by formation of acetic acid.Perchloric acid increased the rate.From variable-temperature studies, Ea=61.5 kJ mol-1 and ΔH(excit.)=59.0 kJ mol-1.The rate of reaction of bromine with hindered ketone, 1, was nearly 900 times as fast as that with the unhindered analogue, acetophenone, under comparable conditions.
- Pinkus, A. G.,Gopalan, R.
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p. 2630 - 2636
(2007/10/02)
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