- Propacetamol crystal form and preparation method thereof
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The invention discloses a propacetamol crystal form and a preparation method thereof, and relates to the technical field of chemical organic synthesis. Acetaminophen and chloroacetyl chloride are usedas starting materials, the propacetamol crystal form is prepared through a chloroacetylation reaction and an ammoniation reaction, and the propacetamol crystal form is not reported in the prior art Propacetamol solid is prepared by utilizing the preparation method, and therefore, the feeding amount can be accurately controlled when the propacetamol hydrochloride is prepared through a subsequent salt forming reaction, the situation that the dosage of hydrochloric acid is too large or too small is avoided, and the problem that in the prior art, the yield and purity of the product propacetamol hydrochloride are seriously affected when the propacetamol hydrochloride is prepared through a propacetamol oily matter is solved.
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Paragraph 0031-0038
(2020/05/02)
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- N,N′-Dialkylaminoalkylcarbonyl (DAAC) prodrugs and aminoalkylcarbonyl (AAC) prodrugs of 4-hydroxyacetanilide and naltrexone with improved skin permeation properties
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N,N′-Dialkylaminoalkylcarbonyl (DAAC) and aminoalkylcarbonyl (AAC) prodrugs of phenolic drugs acetaminophen (APAP) and naltrexone (NTX) are reported. The effects of incorporation of a basic amine group into the promoiety of an acyl prodrug of a phenolic drug on its skin permeation properties are also presented. DAAC-APAP prodrugs were synthesized via a three-step procedure starting with haloalkylcarbonyl esters which were reacted with five different amines: dimethylamine, diethylamine, dipropylamine, morpholine, and piperidine. The spacing between the amino group and the carbonyl group of the acyl group was 1-3 CH2. After the hydrolysis of the ester, the carboxylic acid product was subsequently coupled with the parent drug via a dicyclohexyl carbodiimide (DCC) mediated coupling to yield the DAAC-APAP-HCl prodrugs in excellent yields. The AAC prodrugs were synthesized using commercially available Boc-protected amino acids using DCC or EDCI as coupling agents. The yields of the prodrugs synthesized using these two different methods have been compared. Half-lives (t1/2) of a few members of the DAAC and AAC series were measured in buffer (pH 6.0, 20 mM). The members evaluated in hydrolysis experiments exhibit a t1/2 range of 15-113 min. Among AAC-APAP prodrugs, the isopropyl group in valinate-APAP-HCl exerted a steric effect that increased the t1/2 value for this prodrug compared to alaninate-APAP-HCl or prolinate-APAP-HCl. The 2-morpholinylacetate-APAP prodrug was able to achieve twice the flux of APAP in in vitro diffusion cell experiments through hairless mouse skin.
- Devarajan-Ketha,Sloan
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p. 4078 - 4082
(2011/08/06)
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- P-acetamidophenyl diethylaminoacetate
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A p-acetamidophenol derivative which is soluble in water giving stable aqueous solutions. This derivative is p-acetamidophenyl diethylaminoacetate, optionally in the form of a non-toxic pharmaceutically acceptable acid addition salt, particularly the hydrochloride. This derivative rapidly releases the para-acetamidophenol in the organism.
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