- Carbonic anhydrase catalyzed hydrolysis and decarboxylation. Kinetic studies of enzyme catalyzed decomposition of mono- and disubstituted derivatives of carbonic acid
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The effect of bovine carbonic anhydrase on the stepwise hydrolysis of carbonate diesters is examined. While biphasic enzyme kinetics cannot be detected in the case of bis(4 nitrophenyl) carbonate, it is demonstrated that at pH 10.45 methyl 4 nitrophenyl carbonate is enzymatically hydrolyzed to produce an intermediate monoester, methyl carbonate, which does not undergo enzyme catalyzed decarboxylation. However, it is shown that at pH 7.27 methyl carbonate decarboxylation is accelerated by carbonic anhydrase. The enzymatic pH rate profile for methyl 4 nitrophenyl carbonate release of 4 nitrophenol rises with increasing pH, while the pH dependency for the enzyme catalyzed decarboxylation of methyl carbonate is such that it decreases with increasing pH. In this respect, the kinetic behavior of bovine carbonic anhydrase in regard to methyl 4 nitrophenyl carbonate hydrolysis appears to be similar to that observed in CO2 hydration; in both the rate varies as though dependent on the ionization of a group in the enzyme with pK near 7, only the basic form being active. On the other hand the enzyme catalyzed decarboxylation of methyl carbonate appears to be formally similar to that of bicarbonate; with these two anions the rate varies as though dependent on the ionization of a group in the enzyme of essentially the same pK(7) with only the acid form being active. Although at pH 7.27 the first order rate coefficient, k(buf), for methyl carbonate decomposition is 1.8 times larger than that for bicarbonate dehydration, the second order enzymatic rate coefficient, k(enz), for bicarbonate is three orders of magnitude greater than that for methyl carbonate. The large differences in these k(enz) values are discussed in terms of the role of the labile bicarbonate proton in the mechanism of carbonic anhydrase catalysis.
- Pocker,Guilbert
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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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- PROTEASE INHIBITORS HAVING ENHANCED FEATURES
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Provided herein (among other things) are protease inhibitor compounds having enhanced features, along with methods for administering such compounds. For example, the subject compounds can be administered without concomitant administration of a CYP3A4 inhibitor, have increased therapeutic index and/or increased potency, and are low-resistance inducing in nature.
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Paragraph 0180; 0181
(2017/02/28)
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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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- Bisbenzamidines and bisbenzamidoximes for the treatment of human African trypanosomiasis
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Disclosed are bisbenzamidine and bisbenzamidoxime compounds useful for treatment of treatment of trypanosomiasis. The compounds disclosed are useful for treating mammals infected with parasitic hemoflagellates, in particular Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense.
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Page/Page column 13
(2008/12/06)
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- Novel prodrugs for antimicrobial amidines
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A methods of treating an infection comprises administering a therapeutically effective amount of a compound described by the Formula (I): wherein: X may be O, S, or NR′ wherein R′ is H or loweralkyl; R1 and R2 may be independently selected from the group consisting of H, loweralkyl, oxyalkyl, alkoxyalkyl, cycloalkyl, aryl, hydroxyalkyl, aminoalkyl, and alkylaminoalkyl; R3 and R4 are each independently selected from the group consisting of H, loweralkyl, halogen, oxyalkyl, oxyaryl, and oxyarylalkyl; R5 is represented by a formula selected from the group consisting of: ?wherein: X1, X2, and X3 are independently selected from O and S; and R6 and R7 are independently selected from the group consisting of loweralkyl, aryl, alkylaryl, oxyaryl, an ester-containing substituent, and oxyalkyl; or a pharmaceutically acceptable salt thereof.
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- Prodrugs for amidines: Synthesis and anti-Pneumocystis carinii activity of carbamates of 2,5-bis(4-amidinophenyl)furan
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Syntheses of several carbamate analogues of 2,5-bis(4- amidinophenyl)furan (1) under mild conditions and their evaluation as prodrugs against Pneumocystis carinii pneumonia (PCP) in an immunosuppressed rat model are described. Thus, nine new bis-carbamates: methoxycarbonyl (2), 2,2,2-trichloroethoxycarbonyl (3), ethylthiocarbonyl (4), benzyloxycarbonyl (5), (4-methyl-2-oxo-1,3-dioxol-4-en-5-yl)methoxycarbonyl (6), phenoxycarbonyl (7), 4-fluorophenoxycarbonyl (8), 4-methoxyphenoxycarbonyl (9), and (1-acetoxy)ethoxycarbonyl (10) and a biscarbonate ethoxycarbonyloxy (1) of the bis-amidine 1 have been synthesized and evaluated. The in vivo results show that the 4-fluorophenyl carbamate 8 and the 4-methoxyphenyl carbamate 9 in this series had the best anti-PCP activity by both intravenous and oral administration at a dosage level of 22 mol and 33 μmol/kg/day, respectively. Compounds 3-7 were also more active than the parent drug (1) on oral administration. The acute toxicity usually exhibited by the parent amidine 1 at a dosage level of 22 μmol/kg/day on intravenous administration has been significantly reduced by the prodrug modifications, with the exception of compound 10 which exhibited some toxicity. This report also describes the synthesis of several aryl-alkyl and aryl-aryl carbonates (12- 14, 16-23) as efficient reagents for the preparation of carbamate derivatives from bis-arylamidines.
- Rahmathullah, Syed M.,Hall, James Edwin,Bender, Brendan C.,McCurdy, Donald R.,Tidwell, Richard R.,Boykin, David W.
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p. 3994 - 4000
(2007/10/03)
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- Synthesis and evaluation of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines and 2-Amino-9-(3-alkoxycarbonyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines as potential prodrugs of penciclovir
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A series of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines (1-8) and 2-amino-9-(3-alkoxycarbonyl- oxymethyl-4-alkoxycarbonyloxybut-1-yl)purines (9-12) were synthesized as potential prodrugs of penciclovir. Treatment of 6- deoxypenciclovir
- Kim, Dae-Kee,Lee, Namkyu,Ryu, Do Hyun,Kim, Young-Woo,Kim, Jae-Sun,Chang, Kieyoung,Im, Guang-Jin,Choi, Won-Son,Cho, Yong-Baik,Kim, Key H.,Colledge, Danni,Locarnini, Stephen
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p. 1715 - 1725
(2007/10/03)
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- Stoichiometric solvation effects. Part 3. Product-rate correlations for solvolyses of p-nitrophenyl chloroformate in alcohol-water mixtures
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Rate constants for solvolyses of p-nitrophenyl chloroformate in water, D2O, CH3OD, 50% D2O-CH3OD, and in aqueous binary mixtures of acetone, acetonitrile, ethanol and methanol are reported at 25°C. Product selec
- Koo, In Sun,Yang, Kiyull,Kang, Keumduck,Lee, Ikchoon,Bentley, T. William
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p. 1179 - 1183
(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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- Pentaalkylguanidines as etherification and esterification catalysts
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Several pentaalkylguanidines have been prepared and found to be superior catalysts for the preparation of aryl and aralkyl ethers from carbonates and for the methylation of phenols with dimethylcarbonate.They also act as effective catalysts for esterification of acids with alkyl chloroformates but not for the acetylation of tertiary alcohols with acetic anhydride.
- Barcelo, Gerard,Grenouillat, Denis,Senet, Jean-Pierre,Sennyey, Gerard
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p. 1839 - 1848
(2007/10/02)
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