- Light-induced synthesis of unsymmetrical organic carbonates from alcohols, methanol and CO2under ambient conditions
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The present work describes the first visible light-assisted, metal-free and organic base 1,1,3,3-tetramethyl guanidine (TMG) mediated synthesis of unsymmetrical methyl aryl/alkyl carbonates from the reaction of alcohols, methanol, and CO2 in high to excel
- Saini, Sandhya,Gour, Nand Kishor,Khan, Shafiur Rehman,Deka, Ramesh Chandra,Jain, Suman L.
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supporting information
p. 12800 - 12803
(2021/12/13)
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- CYCLIC AMINES AS BROMODOMAIN INHIBITORS
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The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.
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Paragraph 0590; 0593
(2014/05/25)
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- AROMATIC RING COMPOUND
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Provided is an aromatic ring compound having a GPR40 agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has a GPR40 agonist activity, and is useful as an agent for the prophylaxis or treatment of diabetes and the like.
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Paragraph 0382; 0383
(2015/01/18)
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- A mechanistic study of the [La2(OCH3) 2]4+-and [(1,5,9-triazacyclodo-decane):Zn:(OCH 3)]+-catalyzed methanolysis of carbonates: Possible application for the recycling of bisphenol A polycar
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The kinetics of the methanolysis of seven methyl aryl carbonates (3) and two methyl alkyl carbonates (4) promoted by [12[ane]N3:Zn:(OCH 3)]+ and [La2(OCH3) 2]4+ catalysts (1 and 2, respecti
- Neverov, Alexei A.,Chen, Leanne D.,George, Sean,Simon, David,Maxwell, Christopher I.,Brown, R. Stan
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p. 1139 - 1146
(2013/11/06)
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- C,N-chelated organotin(IV) compounds as catalysts for transesterification and derivatization of dialkyl carbonates
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The potential catalytic activity of selected C,N-chelated organotin(IV) compounds (e.g. halides and trifluoroacetates) for derivatization of both dimethyl carbonate (DMC) and diethyl carbonate (DEC) was investigated. Some tri-, di- and monoorganotin(IV) species (LCN(n-Bu)2SnCl (1), LCN(n-Bu)2SnCl.HCl (1a), LCN(n-Bu) 2SnI (2), LCNPh2SnCl (3), LCNPh 2SnI (4), LCN(n-Bu)SnCl2 (5), L CNSnBr3 (6) and [LCNSn(OC(O)CF 3)]2(μ-O)(μ-OC(O)CF3)2 (7)) bearing the LCN moiety (LCN = 2-(N,N-dimethylaminomethyl) phenyl-) were assessed as catalysts for reactions of both DMC and DEC with various substituted anilines. The catalytic activities of 4 and 7 for derivatization of DMC with p-substituted phenols were studied for comparison with the standard base K2CO3/Silcarbon K835 catalyst (catalyst 8). The composition of resulting reaction mixtures was monitored by multinuclear NMR spectroscopy, GC and GC-MS techniques. In general, catalysts 1, 3 and 7 exhibited the highest catalytic activity for all reactions studied, while some of them yielded selectively carbonates, carbamates, lactam or substituted urea. Copyright
- Weidlich, Tomas,Dusek, Libor,Vystrcilova, Barbora,Eisner, Ales,Svec, Petr,Ruzicka, Ales
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experimental part
p. 293 - 300
(2012/10/07)
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- Indium-catalyzed reaction for the synthesis of carbamates and carbonates: selective protection of amino groups
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We developed a simple, efficient, and selective method for preparing organic carbamates and carbonates using a catalytic amount of indium. A wide range of carbamates and carbonates were synthesized in high yields. The method is also applicable to the selective protection of amino groups under mild conditions.
- Kim, Joong-Gon,Jang, Doo Ok
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experimental part
p. 2688 - 2692
(2009/08/09)
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- Dimethyl carbonate as an ambident electrophile
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(Chemical Equation Presented) The features of various anions having different soft/hard character (aliphatic and aromatic amines, alcohoxydes, phenoxides, thiolates) are compared with regard to nucleophilic substitutions on dimethyl carbonate (DMC), using different reaction conditions. Results are well in agreement with the Hard-Soft Acid-Base (HSAB) theory. Accordingly, the high selectivity of monomethylation of CH2 acidic compounds and primary aromatic amines with DMC can be explained by two different subsequent reactions, which are due to the double electrophilic character of DMC. The first step consists of a hard-hard reaction and selectively produces a soft anion, which, in the second phase, selectively transforms into the final monomethylated product, via a soft-soft nucleophilic displacement (yield >99% at complete conversion, using DMC as solvent).
- Tundo, Pietro,Rossi, Laura,Loris, Alessandro
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p. 2219 - 2224
(2007/10/03)
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- Design, synthesis, and antifolate activity of new analogues of piritrexim and other diaminopyrimidine dihydrofolate reductase inhibitors with ω-carboxyalkoxy or ω-carboxy-1-alkynyl substitution in the side chain
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As part of a search for dihydrofolate reductase (DHFR) inhibitors combining the high potency of piritrexim (PTX) with the high antiparasitic vs mammalian selectivity of trimethoprim (TMP), the heretofore undescribed 2,4-diamino-6-(2′,5′-disubstituted benzyl)pyrido[2,3-d]pyrimidines 6-14 with O-(ω-carboxyalkyl) or ω-carboxy-1-alkynyl groups on the benzyl moiety were synthesized and tested against Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium DHFR vs rat DHFR. Three N-(2,4-diaminopteridin-6-yl)methyl)-2′-(ω-carboxy-1-alkynyl) -dibenz[b,f]azepines (19-21) were also synthesized and tested. The pyridopyrimidine with the best combination of potency and selectivity was 2,4-diamino-5-methyl-6-[2′-(5-carboxy-1-butynyl)-5′-methoxy]benzyl] pyrimidine (13), with an IC50 value of 0.65 nM against P. carinii DHFR, 0.57 nM against M. avium DHFR, and 55 nM against rat DHFR. The potency of 13 against P. carinii DHFR was 20-fold greater than that of PTX (IC50 = 13 nM), and its selectivity index (SI) relative to rat DHFR was 85, whereas PTX was nonselective. The activity of 13 against P. carinii DHFR was 20 000 times greater than that of TMP, with an SI of 96, whereas that of TMP was only 14. However 13 was no more potent than PTX against M. avium DHFR, and its SI was no better than that of TMP. Molecular modeling dynamics studies using compounds 10 and 13 indicated a slight binding preference for the latter, in qualitative agreement with the IC50 data. Among the pteridines, the most potent against P. carinii DHFR and M. avium DHFR was the 2′-(5-carboxy-1-butynyl) dibenz[b,f]azepinyl derivative 20 (IC50 = 2.9 nM), whereas the most selective was the 2′-(5-carboxy-1-pentynyl) analogue 21, with SI values of > 100 against both P. carinii and M. avium DHFR relative to rat DHFR. The final compound, 2,4-diamino-5-[3′-(4-carboxy-1-butynyl)-4′-bromo- 5′-methoxybenzyl]pyrimidine (22), was both potent and selective against M. avium DHFR (IC50 = 0.47 nM, SI = 1300) but was not potent or selective against either P. carinii or T. gondii DHFR.
- Chan, David C. M.,Fu, Hongning,Forsch, Ronald A.,Queener, Sherry F.,Rosowsky, Andre
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p. 4420 - 4431
(2007/10/03)
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- PYRROLE DERIVATIVE
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A novel pyrrole derivative represented by the following formula (1) and a salt thereof: wherein R1 means substituted alkenyl, etc.; R2 means substituted benzoyl, etc.; and R3 to R5 each means hydrogen, alkyl, halogeno, etc. The derivative and salt have antidiabetic activity.
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- Inhibition of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductases by 2,4-diamino-5-[2-methoxy-5-(ω-carboxyalkyloxy)benzyl]pyrimidines: Marked improvement in potency relative to trimethoprim and species selectivity relative to piritrexim
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A series of previously undescribed 2,4-diamino-5-[2-methoxy-5-alkoxybenzyl]pyrimidines (3a-e) and 2,4-diamino-5-[2-methoxy-5-(ω-carboxyalkyloxy)benzyl]pyrimidines (3f-k) with up to eight CH2 groups in the alkoxy or ω-carboxyalkyloxy side chain were synthesized and tested for the ability to inhibit partially purified dihydrofolate reductase (DHFR) from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), Mycobacterium avium (Ma), and rat liver in comparison with two standard inhibitors, trimethoprim (1) and piritrexim (2). The latter drug is known to be extremely potent but shows a marked preference for binding to mammalian DHFR, whereas the former is very selective for the parasite enzymes but is a much weaker inhibitor. The underlying strategy for the synthesis of compounds 3a-k was that a hybrid structure embodying some features of both 1 and 2 might possess a more favorable combination of potency and selectivity than either parent drug. The choice of analogues 3f-k was based on the idea that the acidic ω-carboxyl group might interact preferentially with a basic center in the active site of DHFR from any of the parasite species relative to the active site of mammalian DHFR. In addition, the ω-carboxyl group was expected to improve water solubility relative to 1 or 2. In standardized spectrophotometric assays with dihydrofolate as the substrate and NADPH as the cofactor, 2,4-diamino-5-[(2-methoxy-4-carboxybutyloxy)benzyl]pyrimidine (3g) inhibited Pc DHFR with an IC50 of 0.049 μM and rat DHFR with IC50 of 3.9 μM. Its potency against Pc DHFR was 140-fold greater than that of 1 and close to that of 2, and its selectivity index, defined as the ratio IC50(rat liver)/IC50(P. carinii), was 8-fold higher than that of 1 and > 104fold higher than that of 2. Although it was less potent and less selective against Tg than Pc DHFR, it was very potent as well as highly selective against Ma DHFR, with an IC50 of 0.0058 μM and an IC50(rat liver)/IC50(M. avium) ratio of > 600. Because of this favorable combination of potency and selectivity relative to 1 and 2, compound 3g may be viewed as a promising lead in the search for new antifolates with potential clinical activity against P. carinii and other opportunistic pathogens in patients with AIDS.
- Rosowsky,Forsch,Queener
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p. 233 - 241
(2007/10/03)
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- Concerted mechanisms of the reactions of methyl aryl carbonates with substituted phenoxide ions
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The reactions of 4-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-trinitrophenyl methyl carbonates (NPC, DNPC, and TNPC, respectively) with substituted phenoxide ions are subjected to a kinetic study in water at 25.0 °C, ionic strength 0.2 M (KCl). Production of the leaving groups (the nitro derivatives) is followed spectrophotometrically. Under excess of the phenoxide ions pseudo-first-order rate coefficients (kobsd) are found throughout. Plots of kobsd vs substituted phenoxide concentration at constant pH are linear, with the slope (kN) independent of pH. The Broensted-type plots (log kN vs pKa of the phenols) are linear with slopes β = 0.67, 0.48, and 0.52 for the phenolysis of NPC, DNPC, and TNPC, respectively. The magnitudes of these Broensted slopes are consistent with a concerted mechanism. In the particular case of the phenolysis of NPC the expected hypothetical curvature center of the Broensted plot for a stepwise mechanism should be pKa0 = 7.1 (the pKa of 4-nitrophenol). This curvature does not appear within the pKa range of the substituted phenols studied (5.3-10.3), indicating that these reactions are concerted. The phenolysis of DNPC and TNPC should also be concerted in view of the even more unstable tetrahedral intermediates that would be formed if the reactions were stepwise. The reactions of the same substrates with pyridines are stepwise, which means that substitution of a pyridine moiety in a tetrahedral intermediate by a phenoxy group destabilizes the intermediate perhaps to the point of nonexistence. The kN values for the title reactions are larger than those for the concerted phenolysis of the corresponding ethyl S-aryl thiolcarbonates. The kN values found in the present reactions are subjected to a dual regression analysis as a function of the pKa, of both the nucleophile and leaving group, the coefficients being βN = 0.5 and βig = -0.3, respectively. These coefficients are consistent with a concerted mechanism.
- Castro,Pavez,Santos
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p. 3129 - 3132
(2007/10/03)
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- Ketene acetals from thermolysis of aryloxy methoxy oxadiazolines. Evidence for carbonyl ylide intermediates
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Thermolysis of oxadiazolines (5) in benzene at 110°C leads to ketene acetals (11) as minor products. Carbonyl ylide intermediates (6), and oxiranes (7), presumably in equilibrium with those ylides, are implicated as unstable precursors of the ketene aceta
- Couture, Philippe,El-Saidi, Manal,Warkentin, John
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p. 326 - 332
(2007/10/03)
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- Nucleophilic substitution reactions of phenyl chloroformates
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Methanolysis and aminolysis of phenyl chloroformates in acetonitrile have been investigated.The rates are slow due to initial-state stabilization by strong resonance electron donation from the phenoxy group.In both reactions the large positive values of ρY = 0.8-1.6 and low ΔH(excit.) and ΔS(excit.) values show that the transition state is strongly associative with little bond breaking.This mechanism is supported by the relatively large solvent isotope effect, kMeOH/kMeOD = ca. 2.3-2.5, and by the relatively strong inverse secondary kinetic isotope effect, kH/kD =/ca. 0.74-0.94, involving deuteriated aniline nuclephiles, in addition to a negative value of ρXY.The dependence on aniline basicity, βx(βnuc) =/ca. 0.8, and the ρX values of -2.3 are similar to those corresponding values for the reactions of benzoyl chlorides which have been predicted to react by an associative SN2 mechanism.These observations are consistent with a concerted displacement mechanism for the methanolysis and aminolysis of phenyl chloroformates.
- Yew, Kyoung Han,Koh, Han Joong,Lee, Hai Whang,Lee, Ikchoon
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p. 2263 - 2268
(2007/10/03)
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