- Three-Dimensional Proteome-Wide Scale Screening for the 5-Alpha Reductase Inhibitor Finasteride: Identification of a Novel Off-Target
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Finasteride, a 5-alpha reductase (5α-R) inhibitor, is a widely used drug for treating androgen-dependent conditions. However, its use is associated with sexual, psychological, and physical complaints, suggesting that other mechanisms, in addition to 5α-R inhibition, may be involved. Here, a multidisciplinary approach has been used to identify potential finasteride off-target proteins. SPILLO-PBSS software suggests an additional inhibitory activity of finasteride on phenylethanolamine N-methyltransferase (PNMT), the limiting enzyme in formation of the stress hormone epinephrine. The interaction of finasteride with PNMT was supported by docking and molecular dynamics analysis and by in vitro assay, confirming the inhibitory nature of the binding. Finally, this inhibition was also confirmed in an in vivo rat model. Literature data indicate that PNMT activity perturbation may be correlated with sexual and psychological side effects. Therefore, results here obtained suggest that the binding of finasteride to PNMT might have a role in producing the side effects exerted by finasteride treatment.
- Giatti, Silvia,Di Domizio, Alessandro,Diviccaro, Silvia,Falvo, Eva,Caruso, Donatella,Contini, Alessandro,Melcangi, Roberto Cosimo
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- Production process of adrenal glands
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The invention discloses a production technology for carbazochrome. The production technology comprises the following steps: 1) synthesizing chloracetyl catechol; 2) synthesizing corticosterone hydrochloride; 3) synthesizing adrenaline; and 4) synthesizing the carbazochrome. The production technology for the carbazochrome, disclosed by the invention, has the advantages of simple preparation method,few steps and easiness for operation and control; and an obtained product has good color and luster, good quality, high purity and high yield, can be directly used for production and utilization andhas very good practicability.
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- PREPARATION METHOD FOR HIGH PURITY RACEMIC ADRENALINE
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A preparation method for a racemic adrenaline as represented by formula II. The method may comprise the following steps: compound 1 is directly racemized in an acidic solution to produce compound 2, the acid solution comprising neither sodium bisulfite nor salicylic acid; and specifically comprises (a), in the acid solution of which the pH is 0.5-1.5, compound 1 is placed under the protection of nitrogen gas and, with the reaction temperature being controlled at 75-95° C., stirred and reacted for 1-3 hours; (b) the reaction solution is controlled at a temperature of 5-20° C., into which an activated carbon is added, under the protection of nitrogen gas, stirred for 20-40 minutes, and filtered, then a filtrate is collected; the filtrate is controlled at a temperature of 5-20° C., the pH thereof is adjusted using ammonia to 8.5-9.5, and is filtered when the pH is stabilized, and a filter cake is washed and dried to produce a high purity racemic adrenaline white powder. The weight yield of the product produced per the preparation method is greater than 90%, the chromatographic purity is greater than 96%, and the ee value approaches zero.
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Paragraph 0030-0039
(2020/09/09)
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- Method for preparing racemic-form epinephrine with S-epinephrine
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The invention relates to a method for preparing racemic-form epinephrine with S-epinephrine. The method includes that S-epinephrine shown as the formula II is allowed to react with salicylaldehyde in an acidic medium to prepare racemic-form epinephrine shown as the formula I. With the method that salicylaldehyde is taken as a racemic agent which is capable of being used for converting residual S-epinephrine on split racemic epinephrine into racemic epinephrine; compared with the prior art, the method has the advantages of high racemic conversion rate, few product impurities, good product quality, mild reaction conditions, easiness in control and fitness for industrial production.
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Paragraph 0027; 0028; 0029; 0030; 0031; 0032; 0033-0046
(2017/04/20)
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- PROCESS FOR THE PREPARATION OF OPTICALLY ENRICHED ADRENALINE
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A process for the production of (-)-adrenaline and (-)-adrenaline-L-tartrate is provided. The process provides for a new, efficient and commercially feasible process for the optical resolution of racemic adrenaline. In one aspect, a one pot process for the synthesis of (-)-adrenaline is provided. The process provides a simple and less expensive 5 process that can be used to prepare commercial scale batches of (-)-adrenaline and (-)-adrenaline-L-tartrate of API quality. The process avoids the use of expensive and unpredictable chiral catalysts.
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- A simple two-step synthesis of 2-(alkylamino)-1-arylethanols, including racemic adrenaline, from aromatic aldehydes via 5-aryloxazolidines
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Benzaldehydes react smoothly with nonstabilized azomethine ylides, generated in situ from sarcosine/formaldehyde or N-(methoxymethyl)-N- (trimethylsilylmethyl)benzylamine, to give 5-aryloxazolidines as intermediates. These were converted into 2-(alkylamino)-1-arylethanols in good yields by simple heating in methanol with hydrochloric acid, or by treatment with hydrazine hydrate in ethanol.
- Moshkin, Vladimir S.,Sosnovskikh, Vyacheslav Ya.
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p. 5869 - 5872
(2013/10/21)
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- PROCESSES FOR THE PREPARATION OF EPINEPHRINE
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The invention relates to efficient and cost effective processes for the preparation of pure (-)- epinephrine. More particularly, it relates to processes for the resolution of racemic epinephrine.
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Page/Page column 7
(2009/03/07)
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- Reactivity of adrenaline toward alkoxyl radicals and carbonyl triplet states
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The reactivities of adrenaline toward hydrogen abstraction by the tert-butoxyl radical and the excited triplet state of benzophenone have been examined in solution using laser flash photolysis techniques. The rate constants obtained in acetonitrile-rich solvents are 13 and 1.5 × 108 M-1 s-1 for benzophenone triplet and the tert-butoxyl radical, respectively. Adrenaline is a better hydrogen donor than phenol, but not as efficient as α-tocopherol.
- Cosa, Gonzalo,Scaiano
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body text
p. 4609 - 4614
(2009/03/12)
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- The acid-catalysed racemisation mechanism of catecholamines
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The racemisation rates of (-)-adrenaline (1), ()-isoprenaline (2), (-)-2-(3,4-dimethoxyphenyl)-2-hydroxy-N-isopropylamine (3), (+)-2-(4-meethoxyphenyl)-2-hydroxy-N-isopropylethylamine (4), (+)-2-phenyl-2-hydroxy-N-isopropylehylamine (5), ()-phenylephrine(6), and (+)-1-phenylethanol(7) were compared. The racemisatton rates decreased in the following order: 7> 1 ≈ 2 > 3 ≈ 4 ? 5, 6. In general, the reactivity of the series of the phenylethanolamine compounds (1) - (6) was seen to increase sharply as the electron-releasing ability of the p-substituent of the aromatic nucleus increases. The results strengthen the notion that the acid-catalysed racemisation of catecholamines proceeds via a quinonoid-type intermediate.
- Venter, Daniel P.
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p. 5019 - 5024
(2007/10/02)
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- Esters of 3-(hydroxy or hydroxymethyl)-4-hydroxyphenyl aminomethyl ketones
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Mono-, di- and tri-esters of 3-(hydroxy or hydroxymethyl)-4-hydroxy-alpha-(aminomethyl)benzyl alcohols, obtained by methods involving reduction of the corresponding mono- and di-ester ketones, are useful for producing sympathomimetic effects, such as bronchodilation, of long duration with low cardiovascular stimulating effect, in warm-blooded mammals.
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