- One-step hydroxylation of aryl and heteroaryl fluorides using mechanochemistry
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Simple use of KOH allows the direct F to OH exchange of aromatic and heteroaromatic substrates under mechanochemical conditions. The reaction is performed in the absence of solvent with potassium hydroxide as OH source. As a result, this approach is both more atom economical and environmentally friendly than previously described methods for this transformation.
- Braje, Wilfried,Geneste, Hervé,Rodrigo, Eduardo,Walter, Magnus W.,Wiechert, Rainer
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supporting information
p. 1469 - 1473
(2022/03/07)
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- Radical-anion coupling through reagent design: hydroxylation of aryl halides
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The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described. Key to the success of this approach was the identification of a reducing oxime anion which can interact and couple with open-shell aryl radicals. Experimental and computational studies support the proposed radical-nucleophilic substitution chain mechanism.
- Chechik, Victor,Greener, Andrew J.,James, Michael J.,Oca?a, Ivan,Owens-Ward, Will,Smith, George,Ubysz, Patrycja,Whitwood, Adrian C.
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p. 14641 - 14646
(2021/11/17)
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- Multi-Functional Oxidase Activity of CYP102A1 (P450BM3) in the Oxidation of Quinolines and Tetrahydroquinolines
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Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48-variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation-selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4-dihydro-2-quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L?1 day?1). Other oxidase activities, such as C?C bond desaturation, aromatization, and C?C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy-functionalized derivatives of these building block molecules for synthesis and drug discovery.
- Li, Yushu,Wong, Luet L.
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supporting information
p. 9551 - 9555
(2019/08/06)
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- Application of quebrachitol in hydrolysis reaction of copper-catalyzed aryl halide
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The invention belongs to the technical field of drug synthesis, and provides application of quebrachitol in a hydrolysis reaction of a copper-catalyzed aryl halide. According to the hydrolysis reaction, copper serves as a catalyst, quebrachitol serves as a ligand, and the hydrolysis reaction is carried out on the aryl halide. The invention further provides a catalytic system of the hydrolysis reaction of the aryl halide. The reaction system comprises the copper catalyst, the quebrachitol, alkali and water, and the system is environmentally friendly and is suitable for industrial application.
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Paragraph 0093-0095
(2019/07/16)
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- Synthesis of Phenols: Organophotoredox/Nickel Dual Catalytic Hydroxylation of Aryl Halides with Water
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A highly effective hydroxylation reaction of aryl halides with water under synergistic organophotoredox and nickel catalysis is reported. The OH group of the resulting phenols originates from water, following deprotonation facilitated by an intramolecular base group on the ligand. Significantly, aryl bromides as well as less reactive aryl chlorides served as effective substrates to afford phenols with a wide range of functional groups. Without the need for a strong inorganic base or an expensive noble-metal catalyst, this process can be applied to the efficient preparation of diverse phenols and enables the hydroxylation of multifunctional pharmaceutically relevant aryl halides.
- Yang, Liu,Huang, Zhiyan,Li, Gang,Zhang, Wei,Cao, Rui,Wang, Chao,Xiao, Jianliang,Xue, Dong
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supporting information
p. 1968 - 1972
(2018/02/06)
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- NOVEL QUINOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS FOR PREVENTING OR TREATING CANCER CONTAINING THE SAME
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The present invention refers to an excellent cancer antiproliferative potency relative to the quinoline compounds, a pharmaceutically acceptable salt, or hydrate and, number of active ingredient containing bath method and pharmaceutical composition for the prevention or treatment of cancer disease relates to search, said present invention according to compound, a pharmaceutically acceptable salt thereof, or hydrate number and number and mutant kinase protein kinase activity number of excellent cancer billion billion number activity and thus, new anticancer number is useful as the effective component can be. (by machine translation)
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Paragraph 0147-0148; 0155; 0160-0162
(2017/11/10)
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- Synthesis of Complex Phenols Enabled by a Rationally Designed Hydroxide Surrogate
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The conversion of aryl halides to phenols under mild reaction conditions is a longstanding and formidable challenge in organic chemistry. Herein, we report the rational design of a broadly applicable Pd-catalyzed method to prepare phenols with benzaldehyde oxime as a hydroxide surrogate. These reactions occur under mildly basic conditions and enable the late-stage hydroxylation of several functionally-dense drug-like aryl halides.
- Fier, Patrick S.,Maloney, Kevin M.
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supporting information
p. 4478 - 4482
(2017/04/13)
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- Reagent Design and Ligand Evolution for the Development of a Mild Copper-Catalyzed Hydroxylation Reaction
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Parallel synthesis and mass-directed purification of a modular ligand library, high-throughput experimentation, and rational ligand evolution have led to a novel copper catalyst for the synthesis of phenols with a traceless hydroxide surrogate. The mild reaction conditions reported here enable the late-stage synthesis of numerous complex, druglike phenols.
- Fier, Patrick S.,Maloney, Kevin M.
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supporting information
p. 3033 - 3036
(2017/06/07)
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- Design and synthesis of new 2-anilinoquinolines bearing N-methylpicolinamide moiety as potential antiproliferative agents
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A series of new 2-anilinoquinolines 6a–o possessing the substantial N-methylpicolinamide motif at C5 has been designed and synthesized as sorafenib analogs. The antiproliferative activities of the target compounds were preliminarily appraised against a panel of three human cancer cell lines (MCF-7, SK-BR3, and HCT116), and a selected array was further tested over a panel of approximately 60 cancer cell lines at NCI at 10?μM concentration. Interestingly, compounds 6c, 6d, 6j, 6k, and 6l showed promising selective anticancer activities (growth inhibition >80%) toward certain cancer cells at 10?μM testing dose. Compounds 6d and 6j were advanced to five-dose testing mode to determine their GI50 values and compared with our previously reported ureidoquinoline B and sorafenib as reference compounds. The 4-chloro-3-trifluoromethylaniline derivative 6j manifested superior potency than both compound B and sorafenib over eleven and eight cell lines, respectively. It showed GI50 values of 0.36, 0.66, 0.68, and 0.60?μM against the breast MDA-MB-468, renal A498, and melanoma SK-MEL-5 and UACC-62 cell lines, respectively. Moreover, both 6d and 6j exerted low cytotoxic effects against HFF-1 normal cell line. Furthermore, compounds 6d and 6j were tested against both B-RafV600E and C-Raf kinases and displayed modest inhibitory activities, which were justified by molecular docking study. Compound 6j could serve as a promising candidate for further development of potent anticancer chemotherapeutics.
- El-Damasy, Ashraf Kareem,Seo, Seon Hee,Cho, Nam-Chul,Pae, Ae Nim,Kim, Eunice Eunkyeong,Keum, Gyochang
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- Novel 5-substituted-2-anilinoquinolines with 3-(morpholino or 4-methylpiperazin-1-yl)propoxy moiety as broad spectrum antiproliferative agents: Synthesis, cell based assays and kinase screening
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A series of new 2-anilinoquinolines possessing 3-(morpholino or 4-methylpiperazin-1-yl)propoxy moiety at C5 of quinoline has been designed and synthesized as potential anticancer agents. Their antiproliferative activities were evaluated against a panel of 60 cancer cell lines at NCI and compared with gefitinib as a reference compound. Most of the tested compounds displayed potent and broad spectrum antiproliferative activities. Compounds 7d, 7f and 7g showed strong inhibitory and lethal effects at 10?μM concentration. Moreover, they manifested superior potencies and efficacies than gefitinib across the most tested cell lines. Compound 7d, with 4-chloro-3-trifluoromethylphenyl group, proved to be the most potent and efficacious derivative in this series, with mean GI50and TGI values of 1.62?μM and 3.47?μM, respectively. Kinase screening of 7d against a panel of 47 oncogenic kinases revealed its selective inhibitory effect (96% inhibition) towards TrkA kinase. Furthermore, the most potent compounds showed low cytotoxic effects against HFF-1 normal cell line.
- El-Damasy, Ashraf Kareem,Cho, Nam-Chul,Pae, Ae Nim,Kim, Eunice Eunkyeong,Keum, Gyochang
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p. 3307 - 3312
(2016/07/12)
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- METALLOENZYME INHIBITOR COMPOUNDS
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The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
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Page/Page column 25-26
(2013/02/28)
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- Synthesis of 5-hydroxyquinolines
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A series of 5-hydroxyquinolines has been prepared via the Skraup reaction. Several regioisomers were made either by selective displacement of a leaving group or by using a bromo substituent as a blocking group. The bromo group was found to be an excellent blocking group due to its stability during the Skraup reaction and easy removal thereafter. Halides at the 5-position of quinoline were found to be much more reactive than those at the 7- and 8-positions. Finally, we have also found a unique method to reduce the pyridyl ring on quinolines, leaving a halogen substituent untouched.
- Li, Jianke,Kung, Daniel W.,Griffith, David A.
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scheme or table
p. 3876 - 3878
(2010/08/19)
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- A simple deprotection of triflate esters of phenol derivatives
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Efficient conversion of aryl triflates into the corresponding phenols has been accomplished with Et4NOH. In contrast to other cleavage reactions, such functional groups as nitro, ketone, halogen, amide and sulfonamide groups were intact under the reaction conditions. This mild removal of the trifluoromethanesulfonyl group would serve a new protecting group of phenols.
- Ohgiya, Tadaaki,Nishiyama, Shigeru
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p. 6317 - 6320
(2007/10/03)
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- A practical route to quinolines from anilines
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A practical route to quinoline from anilines through acid-mediated cyclization of 3-(N-aryl-N-sulfonylamino)propionaldehydes has been developed. Treatment of the cyclization products, dihydroquinoline intermediates with KOH in DMSO leads to substituted quinolines.
- Tokuyama, Hidetoshi,Sato, Masashi,Ueda, Toshihiro,Fukuyama, Tohru
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p. 105 - 108
(2007/10/03)
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- Process for converting hydroxy heteroaromatics to arylamines
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A process of converting a hydroxy heteroaromatic compound to an arylamine, comprising the steps of: (1) treating a salt of a hydroxy heteroaromatic compound with an alkylating agent; and (2) treating the reaction mixture with a Smiles solvent system and raising the temperature of the reaction mixture; and A compound made according to the above process.
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- 10,11-Methanodibenzosuberane derivatives
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10,11-Methanodibenzosuberane derivatives, i.e., the compounds of Formula I: STR1 wherein: A is --CH2 --CH2 --, --CH2 --CHRa --CH2 --, or --CH2 --CHRa --CHRb --CH2 --, where one of Ra or Rb is H, OH, or lower acyloxy, and the other is H; R1 is H, F, Cl or Br; R2 is H, F, Cl or Br; and R3 is heteroaryl or phenyl optionally substituted with F, Cl, Br, CF3, CN, NO2 or OCHF2 ; and the pharmaceutically acceptable salts thereof, are useful chemosensitizing agents, e.g., for cancer chemotherapy, particularly for treating multidrug resistance.
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- Probing the TiO2 photocatalytic mechanisms in water purification by use of quinoline, photo-fenton generated OH. radicals and superoxide dismutase
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In an attempt to improve our understanding of the basic mechanisms of the degradation of aromatic pollutants in water by TiO2 photocatalysis, quinoline (benzo[b]pyridine) was selected as a molecular probe, principally because of the difference in electron density over its two rings. This study was based on the identification and quantification of the primary products or principal secondary products of quinoline degradation either by TiO2 photocatalysis at pH 3 and 6 or by OH. radicals generated via the photo-Fenton reaction (Fe(II/III)-H2O2-UV) at pH 3. In this latter case, the three major products were those expected from the preferential electrophilic attack of OH. radicals on the electron-richer benzene moiety, viz., 5-, and 8-hydroxyquinolines and quinoline-5,8-dione derived from them. TiO2 photocatalysis did not yield this dione, and at the same percentages of degraded quinoline, the amounts of 5-hydroxyquinoline were lower by a factor of ca. 2 at pH 3 and ca. 10 at pH 6 (those of the 8-isomer were also decreased but no accurate measurements were obtained). In addition, at pH 6, we observed marked increases in the amounts of products corresponding to the oxidation of the pyridine moiety, viz., 4-quinolinone and especially 2-aminobenzaldehyde (the major product) and its N-formyl derivative. These results show that oxidative steps in TiO2 photocatalysis do not involve only OH. radicals. It was also observed that, at pH 6, superoxide dismutase (SOD), which catalyzes the elimination of O2.- species, decreased the TiO2 photocatalytic rate of quinoline disappearance, almost suppressed the formation of 2-aminobenzaldehyde, and lowered the amount of 4-quinolinone. The SOD and pH effects suggest a mechanism involving quinoline activation by hole transfer, followed by superoxide addition to the resulting radical cation. The nucleophilic character of superoxide implies addition to the pyridine moiety, i.e., with a regioselectivity opposite that of the OH. radical pathway.
- Cermenati, Laura,Pichat, Pierre,Guillard, Chantal,Albini, Angelo
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p. 2650 - 2658
(2007/10/03)
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- Quinolinoxy phenylsulphonamides
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New phenylsulphonamide of the formula in which STR1 R1 represents a pyridyl, quinolyl or isoquinolyl radical which is unsubstituted or substituted by halogen, alkyl, cycloalkyl, alkoxy, cyano, nitro, halogenoalkyl, halogenoalkoxy, alkoxycarbonyl or alkylsulphonyl, R2 represents hydrogen, cyano, nitro, halogen, alkyl, alkoxy, halogenoalkyl, halogenoalkoxy or alkoxycarbonyl, R3 represents an aryl radical which is unsubstituted or monosubstituted, disubstituted or trisubstituted by halogen, halogenoalkyl, halogenoalkoxy, alkyl, alkoxy, alkylthio, alkylsulphonyl, cyano, nitro or alkoxycarbonyl, the substituents being identical or different, or represents pentafluorophenyl or represents a straight-chain, branched or cyclic alkyl which is unsubstituted or substituted by halogen, aryl, aryloxy, cyano, alkoxycarbonyl, alkoxy, alkylthio or trifluoromethyl, and X represents an --O--, --A--B-- or --B--A-- group where A denotes --O--, STR2 and B denotes --CH2 -- or STR3 where R1 does not represent a pyridyl radical when x represents an --O-- group, and salts thereof are prepared by reacting appropriate amines with sulphonyl halides. The substituted phenylsulphonamides can be employed as active compounds for inhibiting enzymatic reactions and for inhibiting thrombocyte aggregations.
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- Solvolysis of the Quinoline 5,6- and 7,8-Oxides: Effect of the Ring Nitrogen
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pH-rate profiles for the hydrolysis of quinoline arene oxides were measured in 1:9 dioxane-water at 25 deg C (0.1 M NaClO4) and compared with the parent carbocylic compound naphthalene 1,2-oxide.Unlike naphthalene 1,2-oxide whose hydrolysis rate shows a first-order dependence on hydronium ion concentration (kH) below pH 5, rates for the quinoline 5,6- and 7,8-oxides show a kH reaction (0.14 and 1.54 M-1 s-1 for quinoline 5,6- and 7,8-oxides, respectively), but plateau below pH 2-3. pH-independent rate constants in the low-pH plateau are 2.7E-5 and 1.7E-3 s-1for the 5,6- and 7,8-oxides, respectively.On the basis of studies of the N-methyl cation of the 5,6-oxide (kobsd -1 at pH 1.8), it is concluded that the low-pH plateau is due to lack of reactivity for the N-protonated quinoline oxides.Also unlike naphthalene oxide, the quinoline oxides show a reaction with hydroxide ion (kOH rate) that results in the formation of trans dihydrodiols.In acid, quinoline 5,6-oxide, but not quinoline 7,8-oxide, gives a significant yield (20percent) of the trans dihydrodiol product and provides the first example of a benzo-ring arene oxide that forms dihydrodiol product under acidic conditions.Other products of the acid-catalyzed reaction of the 5,6-oxide are 5- (73percent) and 6- (7percent) hydroxyquinolines.The 7,8-oxide upon solvolysis in acid gave exclusively 8-hydroxyquinoline.The 100-1000 fold decrease in reactivity of the quinoline oxides, relative to naphthalene oxide in the pH range of 1-10, can be accounted for in terms of the presence of their ring nitrogens and the differences in the pKa values of these nitrogens.
- Bushman, Daniel R.,Sayer, Jane M.,Boyd, Derek R.,Jerina, Donald M.
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p. 2688 - 2691
(2007/10/02)
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- ARENE OXIDES AND trans-DIHYDRODIOLS OF QUINOLINE
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Arene oxides and trans-dihydrodiols at the 5,6- and 7,8-positions of quinoline have been synthesized.High stability of both arene oxides allowed identification of the 5,6-oxide as a liver microsomal metabolite of quinoline.Both arene oxides are converted to trans-dihydrodiols by microsomal epoxide hydrolase.
- Agarwal, S. K.,Boyd, D. R.,Porter, H. P.,Jennings, W. B.,Grossman, S. J.,Jerina, D. M.
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p. 4253 - 4256
(2007/10/02)
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- TOTAL REACTIVITY OF PYRIDINE AND QUINOLINE VIA THE REACTIONS OF ARYLBENZOATES WITH HYDROXIDE ION. APPARENT SUBSTITUENT CONSTANS FOR SOME N-HETEROAROMATIC GROUPS
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A new set of apparent ? values was evaluated for the aza substitution of all positions in pyridyl and quinolyl groups on the basis of the alkaline hydrolysis of aryl benzoates.The enhanced reactivities of 4-pyridyloxy- and 4-quinolyloxy- groups were first estimated quantitatively.
- Sawada, Masami,Ichihara, Masaharu,Ando, Takashi,Yukawa, Yasuhide,Tsuno, Yuho
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p. 4733 - 4736
(2007/10/02)
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- Imidazo[1,2-a]quinolines
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The invention relates to imidazo[1,2-a]quinolines of formula (I) STR1 and their pharmaceutically acceptable acid addition salts. In formula I R1 and R2 which may be the same or different each represent hydrogen, lower alkyl, lower alkoxy, trifluoromethyl or halogen, R3 and R4 which may be the same or different each represent lower alkyl and R5 represents hydrogen, lower alkyl, aryl or arylloweralkyl. The compounds possess hypotensive activity.
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