200880-31-5Relevant articles and documents
New enzymatic and chemical approaches to enantiopure etodolac
Brenna, Elisabetta,Fuganti, Claudio,Fuganti, Daniela,Grasselli, Piero,Malpezzi, Luciana,Pedrocchi-Fantoni, Giuseppe
, p. 17769 - 17780 (1997)
(+)- and (-)-etodolac enantiomers were prepared both by classical resolution via crystallisation of diastereoisomeric salts with (+) and (-)-α-methylbenzylamine, and by suitable manipulation of derivatives (-)-3- and (+)-4, obtained by lipase-catalysed kinetic resolution of racemic 3. X-ray diffraction analysis of the 4-bromobenzoate derivative of (+)-3, obtained from enantiopure acetate (+)-4, allowed us to determine the absolute (R) configuration of (-)-etodolac.
Method for preparing etodolac methyl ester
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Paragraph 0050-0087, (2020/07/13)
The invention provides a method for preparing etodolac methyl ester, and relates to the technical field of organic synthesis. The method provided by the invention comprises the following steps: (1) mixing reaction raw materials, and carrying out cyclization reaction at 20-25 DEG C to obtain a reaction solution, wherein the reaction raw materials comprise 7-ethyltryptophol, methyl 3-oxovalerate, trimethyl halosilane and methanol, and do not comprise concentrated sulfuric acid, and the trimethyl halosilane is trimethyl chlorosilane or trimethyl bromosilane; and (2) cooling the reaction solutionto 10-15 DEG C, and filtering to obtain etodolac methyl ester and a mother solution. The method provided by the invention is high in yield, and concentrated sulfuric acid which has great harm and easily causes product oxidation is not used. Furthermore, the product yield is further improved through continuous application of the mother liquor, almost quantitative products can be obtained, the workload of solvent treatment is reduced, the operation is simple and convenient, and trimethyl halosilane is easy to recycle and reuse.
Synthesis, anticancer activity, and molecular modeling of etodolac-thioether derivatives as potent methionine aminopeptidase (type II) inhibitors
?oruh, I??l,?evik, ?zge,Yelek?i, Kemal,Djikic, Teodora,Kü?ükgüzel, ?. Güniz
, (2018/03/29)
A series of (R,S)-1-{[5-(substituted)sulfanyl-4-substituted-4H-1,2,4-triazole-3-yl]methyl}-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indoles (5a–v) were designed and synthesized using a five-step synthetic protocol that involves substituted benzyl chlorides and (R,S)-5-[(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)methyl]-4-substituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones in the final step. The synthesized derivatives were evaluated for cytotoxicity and anticancer activity in vitro using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric method against VERO, HEPG2 (human hepatocellular liver carcinoma), SKOV3 (ovarian carcinoma), MCF7 (human breast adenocarcinoma), PC3 and DU145 (prostate carcinoma) cells at 10?5 M (10 μM) for 24 h. Compounds 5d and 5h showed the best biological potency against the SKOV3 cancer cell line (IC50 = 7.22 and 5.10 μM, respectively) and did not display cytotoxicity toward VERO cells compared to etodolac. Compounds 5k, 5s, and 5v showed the most potent biological activity against the PC3 cancer cell line (IC50 = 8.18, 3.10, and 4.00 μM, respectively) and did not display cytotoxicity. Moreover, these compounds were evaluated for caspase-3, -9, and -8 protein expression and activation in the apoptosis pathway for 6, 12, and 24 h, which play a key role in the treatment of cancer. In this study, we also investigated the apoptotic mechanism and molecular modeling of compounds 5k and 5v on the methionine aminopeptidase (type II) enzyme active site in order to get insights into the binding mode and energy.
