Inhibition ketone group

The analogous methyl ketone and trifluoromethyl alcohol were foimd to be inactive, clearly showing the importance of the trifluoromethyl ketone for HDAC inhibition. Regrettably, the trifluoromethyl ketone group demonstrated a half-Hfe of only 0.5 h and a low i.v. exposure in mice at 10 mg/kg. Another obstacle faced by these molecules is their poor aqueous solubihty. 

Confirming the importance, for the biological activity,10-n of a keto group in the sugar moiety, the antiviral activity of some keto-C-nucleo-sides has also been reported.13 From this study, it was clear that the presence of a ketone group in these nucleosides, as in 4 -ketonucleoside 50a, gave a compound able to inhibit the replication of murine leukemia virus at nontoxic concentrations. 

An acetoxy group at C-21 inhibits reaction of the 20-ketone with semi-carbazide hydrochloride,but in buffered medium 20-semicarbazones can be prepared in high yield even from 17-hydroxy-21-acetoxy compounds. ... 

Cyanohydrins are prepared from unsubstituted 20-ketones by the exchange procedure but not in the presence of a diluent. A 17a-hydroxyl group inhibits the exchange reaction but 20-ketones react with potassium cyanide even in the presence of Ha-bromo or 21-acetoxy substituents. 

An adjacent tnfluoromethyl group sharply increases the electrophilic character of the carbonyl carbon Compounds that readily form hydrates and hemiacetals show a time-dependent reversible mhibition of the en yme acetylcholinesterase (equation 2), in which the tight complex makes inhibition only partially reversible [75] In comparison with a nonfluormated analogue, several aliphatic ketones flanked by CFj and CF2 groups, are exceptionally potent reversible inhibitors of acetylcholinesterase, as documented by companson of inhibition constants shown in equation 3 [16 ... 

The reaction is sensitive to the presence of water, which inhibits the migration of the third alkyl group and leads to dialkyl ketones (see Chapter 12, Section II). The convenience of the hydroboration reaction combined with the use of carbon monoxide at atmospheric pressure provides the most accessible route to many trialkylcarbinols. 

As mentioned in the preceding section, the presence of water during the reaction of trialkylboranes with carbon monoxide inhibits the migration of the third alkyl group and leads to production of dialkyl ketones (i). This fact can be employed to advantage for the preparation of dialkyl ketones as shown in the scheme. 

Aldehyde reductases are a group of isoenzymes that catalyze the NADPH-specific reduction of aldehydes. Ketones do not serve as substrates for these enzymes. The best substrates for aldehyde reductase are aromatic aldehydes and those aldehydes obtained through metabolism of biogenic amines. The species distribution, specificity, and inhibition of aldehyde reductases have been reviewed (792). 

Poly(ether ketone)s 3, 4, 5, 6, and 7 were soluble in polar aprotic solvents such as DMAc and NMP and in chlorinated solvents such as chloroform. The improved solubility of these fluorinated poly(ether ketone)s can be explained by the presence of both the flexible hexafluoroisopropylidene groups and the bulky 1,4-naphthalene moieties, which inhibit polymer crystallization and facilitate the penetration of solvent molecules between the polymer chains. 

Ethanol is both an inducer and substrate of CYP2E1. Indeed, CYP2E1 seems to be structurally geared to favor small volatile molecules such as ketones, aldehydes, alcohols, halogenated alkenes, and alkanes as substrates (36). Moreover, many of these same compounds, like ethanol, are inducers of the enzyme. A major mechanism by which this diverse group of compounds appears to initiate induction is by inhibiting normal enzyme degradation. 

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