17175-16-5Relevant articles and documents
Carbonic anhydrase catalyzed hydrolysis and decarboxylation. Kinetic studies of enzyme catalyzed decomposition of mono- and disubstituted derivatives of carbonic acid
Pocker,Guilbert
, p. 70 - 78,71,75 (1974)
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.
PROTEASE INHIBITORS HAVING ENHANCED FEATURES
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Paragraph 0180; 0181, (2017/02/28)
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.
Bisbenzamidines and bisbenzamidoximes for the treatment of human African trypanosomiasis
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Page/Page column 13, (2008/12/06)
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.
