Inhibitor acetylenic

The possible mechanisms of inhibition of flavin by (—)-deprenyl, as an irreversible acetylenic inhibitor, were studied by ab initio methods with the 6-31G basis set using simplified model compounds, 3-formyl-2-imino-l-hydroxypyrazine, and propargylamine. The formation of two energetically stable cyclic adducts, the 0,N adduct 286 and a C,N adduct, was shown <1999THA147>. 

Fowler CJ, Mantle TJ, Tipton KF. The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, 1-deprenyl and pargyline. Biochem Pharmacol 1982 31(22) 3555-3561. 

Fan PW, Gu C, Marsh SA, et al. Mechanism-based inactivation of cytochrome P450 2B6 by a novel terminal acetylene inhibitor. Drug Metab Dispos 2003 31(1) 28—36. 

In Perlplaneta amerlcana CA, no accumulation of methyl farnesoate was noted with acetylenic Inhibitors of JH III biosynthesis, although this effect was observed with methylenedioxyphenyl Inhibitors (19). 

Helmkamp GM Jr, Rando RR, Brock DJH, Bloch K. B-Hydroxy-decanoyl thioester dehydrase. Specificity of substrates and acetylenic inhibitors. J. Biol. Chem. 1968 243 3229-3231. 

In the course of studying some acetylenic inhibitors in hydrochloric acid, a number of different isotherm type correlation were found. Thus Fig.10 shows a Langmuir plot for 2-butyne-l, -diol in 6N hydrochloric acid under aerated conditions. Two different commercial products of this compound were used. It is shown that the straight line relationship is obtained with a good reproducibility over three orders of magnitude of inhibitor concentration. In the light of what was said above, this was a surprising result, however, it corresponds to other similar observations reported in the literature. 

A complete and extensive rational for the rejection of adsorption theroy in the present case would easily go beyond the frame work of this paper. However, since in the area of acetylenic inhibitors the build-up of surface films up to 200 A has already been observed (.2 ), it maybe more fruitful to follow this line of reasoning. Further experimental effort,of course, ought to attempt to clarify the nature of this surface film. The above described effects such as the acid and the oxygen effect are not immediately obvious if such a surface film is of the nature shown in Table 6. However, some observations involving the de-... 

The chemical basis of action of acetylenic inhibitors seems to reside mainly in the fact that acetylenes can be enzymically converted into conjugated allenes. The latter compounds are powerful Michael acceptors... 

Enzymes capable of generating a carbanion or a carbanion-like intermediate adjacent to an acetylene are susceptible to irreversible inhibition by these acetylenic reagents. Flavin-linked and pyridoxal-linked enzymes and isomerases have proved to be good candidates for inhibition by the acetylenic inhibitors. This is the case because these enzymes are generally involved in C—bond abstraction with concomitant carbanion or car-banion-Iike intermediate formation. However, the critical factor is the formation of a free valance adjacent to the acetylenic imit. An enz3rme that could do so is a candidate for inhibition by these inhibitors. Thymi-dylate synthethase, for example, should be irreversibly inhibited by 5-ethynouracil the free valance would be generated adjacent to the acetylene by means of an enzyme-catalyzed nucleophilic addition to the uracil. ... 

Scott et aL (1971, 1974) have found that the enzymatic synthesis of 6-MSA could be inhibited by the following acetylenic inhibitors 3-hexynoyl-A -acetylcysteamine, 2-hexynoyl-A-acetylcysteamine, and 3-pentynoyl-A -ace-tylcysteamine at very low concentrations (10 M). This result is similar to the studies obtained by Brock and Bloch (1966), who found that 3-decynoyl-A-acetylcysteamine at low concentrations inhibits the unsaturated fatty acid synthetase of E. coli. The mechanism of action has been shown to be the inhibition of the enzyme / -hydroxydecanoyl thioester dehydrase. 3-Decynoyl-A-acetylcysteamine has been shown by Brock and Bloch (1966)... 

In order to clarify the timing of this dehydration, Scott et al. (1974) have studied the oxidation of NADPH to NADP" in the presence of the acetylenic inhibitor. These studies show that (a) at an acetylenic inhibitor concentration ( Q M) which completely blocks 6-MSA synthesis, there is still a noticeable oxidation of NADPH to NADP and (b) when A -ethylmaleimide is used at a concentration that completely blocks 6-MSA synthesis, there is no oxidation of NADPH to NADP. This experimental evidence suggests that the acetylenic inhibitor must act after the reduction step. These inhibition studies can, therefore, be considered indirect proof that the reduction step does not occur at the C(8) carbon, but probably at the C(6) stage. 

Acetylene is condensed with carbonyl compounds to give a wide variety of products, some of which are the substrates for the preparation of families of derivatives. The most commercially significant reaction is the condensation of acetylene with formaldehyde. The reaction does not proceed well with base catalysis which works well with other carbonyl compounds and it was discovered by Reppe (33) that acetylene under pressure (304 kPa (3 atm), or above) reacts smoothly with formaldehyde at 100°C in the presence of a copper acetyUde complex catalyst. The reaction can be controlled to give either propargyl alcohol or butynediol (see Acetylene-DERIVED chemicals). 2-Butyne-l,4-diol, its hydroxyethyl ethers, and propargyl alcohol are used as corrosion inhibitors. 2,3-Dibromo-2-butene-l,4-diol is used as a flame retardant in polyurethane and other polymer systems (see Bromine compounds Elame retardants). 

R SiH and CH2= CHR interact with both PtL and PtL 1. Complexing or chelating ligands such as phosphines and sulfur complexes are exceUent inhibitors, but often form such stable complexes that they act as poisons and prevent cute even at elevated temperatures. Unsaturated organic compounds are preferred, such as acetylenic alcohols, acetylene dicarboxylates, maleates, fumarates, eneynes, and azo compounds (178—189). An alternative concept has been the encapsulation of the platinum catalysts with either cyclodextrin or in thermoplastics or siUcones (190—192). 

Chemical Reactivity - Reactivity with Water Reacts vigorously with water to form highly flammable acetylene gas which can spontaneously ignite Reactivity with Common Materials Reacts with copper and brass to form an explosive formulation Stability During Transport Stable but in absence of water Neutralizing Agents for Acids and Caustics Not pertinent Polymerization Not pertinent Inhibitor of Polymerization Not pertinent. 

Acetylenic compounds have been described for inhibition in acid solutionsTypical inhibitors include 2-butyne-l,4-diol, l-hexyne-3-ol and 4-ethyl-l-octyne-3-ol. 

Reaction of adsorbed inhibitors In some cases, the adsorbed corrosion inhibitor may react, usually by electro-chemical reduction, to form a product which may also be inhibitive. Inhibition due to the added substance has been termed primary inhibition and that due to the reaction product secondary inhibition " . In such cases, the inhibitive efficiency may increase or decrease with time according to whether the secondary inhibition is more or less effective than the primary inhibition. Some examples of inhibitors which react to give secondary inhibition are the following. Sulphoxides can be reduced to sulphides, which are more efficient inhibitorsQuaternary phosphonium and arsonium compounds can be reduced to the corresponding phosphine or arsine compounds, with little change in inhibitive efficiency . Acetylene compounds can undergo reduction followed by polymerisation to form a multimolecular protective film . Thioureas can be reduced to produce HS ions, which may act as stimulators of... 

The four mechanisms discussed above, of the action of inhibitors remain essentially unchanged. Further work on acetylenic alcohols has indicated that barrier films can form owing to crosslinking by hydrogen bonding and synergistic interactions . Theoretical treatments of the electrochemical... 

Butadiene CH2=CHCH= H2 Cu Acetylide, Vinyl Acetylene Ethylene Air (Peroxides) > 300 114 Inhibitor — t-Butyl Catechol — 115ppm Activation 12.0 429 Self-polymerization above RT or press... 

In stimulation fluids containing concentrated HCl, the partial substitution of water by alcohols such as methanol, ethanol, and glycerol increases the corrosivity of the acid fluids and reduces the efficiency of the corrosion inhibitors [1148]. This effect is especially important for fatty amine-based inhibitors. For products containing acetylenic-type inhibitors the detrimental effect is less important and a weight loss may be maintained within acceptable limits using slightly higher, but still reasonable, levels of inhibitor. 

Corrosion inhibition is primarily associated with acidizing. Buffered hydrofluoric acid compositions have been shown to be less corrosive (147). Corrosion inhibitors are designed to reduce the rate of reaction of fluid with metal surfaces, generally by forming films on the surfaces. Acetylenic alcohols and amines are frequently components of corrosion inhibitor blends. Other compounds that have been used include nitrogen heterocyclics, substituted thioureas, thiophenols, and alpha-aminoalkyl thioethers (148). 

Corrosion of steel during oil well acidizing or acid pickling treatments can be controlled effectively and economically with organic corrosion inhibitors. These additives interact with the steel surface to form an adherent barrier, the nature of which depends on the additives physicochemical properties. Work to date has established that acetylenic alcohols chemisorb and subsequently polymerize on steel surfaces (1-5"). a,/MJnsaturated aldehydes and a-alkenyl-phenones appear to behave in a similar manner (6j7"). The nature of Current address Amoco Production Company, Tulsa, OK... 

An emulsion, formed during extraction of a strongly alkaline liquor with trichloroethylene, decomposed with evolution of the spontaneously flammable gas, dichloro-acetylene [1]. This reaction could also occur if alkaline metal-stripping preparations were used in conjunction with trichloroethylene degreasing preparations, some of which also contain amines as inhibitors, which could also cause the same reaction [2], Apparently accidental contact of the solvent with potassium hydroxide solution led to generation of flames in the charging port of a stirred reactor [3], See Tetrachloroethylene Sodium hydroxide... 

The 1,3-dipolar cycloaddition of azidofurazans to acetylenes afforded 1,2,3-triazoles linked with furazan cycle <2000CHE91>. Treatment of 3-azido-2-amino-l,2,5-oxadiazole 194 with ethyl 4-chloroacetoacetate gives access to the functionalized [l,2,3]-triazoles 195, which are good precursors for GSK-3 inhibitors with favorable water solubility (Equation 38) <2003JME3333>. 

The final steps in a total synthesis of (+ )-gloeosporone (3, a natural germination inhibitor of a fungus) required oxidation of the acetylene group of 1 to a diketone group. The oxidation was carried out in 74% yield by the catalytic Ru02 procedure of Sharpless. On liberation (pyridine-HF) of the C7-hydroxyl group, the hydroxy... 

Thus, it would be reasonable to expect that the acetylenic group would be metabolized to a carboxylic acid. While the acid metabolite has not been detected, ethinyl estradiol is a suicide substrate inhibitor of CYP2B6 consistent with a reactive ketene being formed as an intermediate (142). In addition, there is a rearrangement product (4) shown in Figure 4.75. 

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