- Synthesis method of ozagrel sodium
-
The invention discloses a synthesis method of ozagrel sodium, and belongs to the technical field of medicines. The synthesis method comprises the following steps: (1), taking 4-bromobenzyl bromide asa starting material, and reacting with imidazole under an alkaline condition to generate a 1-(4-bromobenzyl)-1H-imidazole intermediate 1; (2), enabling 1-(4-bromobenzyl)-1H-imidazole to react with acrylate under the catalysis of palladium acetate to generate an ozagrel ester intermediate 2; and (3), carrying out alkaline hydrolysis on ozagrel ester to obtain an ozagrel sodium product. The synthesis method disclosed by the invention has the advantages of easily available raw materials, low price cost, few steps, small pollution and the like, and is suitable for industrial production.
- -
-
Paragraph 0048-0049
(2020/07/12)
-
- Preparation method of Ozagrel sodium
-
The invention discloses a preparation method of Ozagrel sodium. The method comprises the following steps: performing a bromination reaction on ethyl 4-methylcinnamate and N-bromo-succinimide by takingacetonitrile as a solvent under the triggering of azodiisobutyronitrile, so as to obtain ethyl 4-bromomethylcinnamate; performing a condensation cyclization reaction on the ethyl 4-bromomethylcinnamate and imidazole by taking sodium hydroxide as an acid-binding agent and taking tetrahydrofuran as a solvent, so as to obtain imidazole ethyl 4-methylcinnamate; performing alkali hydrolysis on the imidazole ethyl 4-methylcinnamate, so as to obtain the Ozagrel sodium. According to the preparation method, the condensation cyclization reaction is performed by taking the sodium hydroxide as the acid-binding agent and taking the tetrahydrofuran as the solvent, so that the finally obtained product does not contain toxic components, the yield and the purity of the product can be effectively improved,and the content of genotoxic impurities (the ethyl 4-bromomethylcinnamate and ethyl 4-dibromomethylcinnamate) in the product is zero.
- -
-
Paragraph 0033; 0042; 0043; 0044; 0069; 0071
(2018/04/02)
-
- Preparation method of ozagrel
-
The invention provides a preparation method of ozagrel, which is characterized by comprising the following steps of: adding ozagrel hydrochloride monohydrate into purified water, heating to dissolve the ozagrel hydrochloride monohydrate, adding alkali liquor, carrying out cooling and crystallization after stirring, and carrying out extraction filtration to obtain an ozagrel crude product; carrying out recrystallization on the ozagrel crude product in mixed solution of methyl alcohol and water to obtain an ozagrel finished product. The preparation method is simple and efficient to operate and easy to control, and purity of the obtained ozagrel accords with the requirements of the Japanese pharmacopoeia.
- -
-
Paragraph 0046; 0047; 0048; 0049; 0050; 0051; 0052; 0053
(2017/06/29)
-
- Prominent inclusion effect of dimethyl-β-cyclodextrin on photoisomerization of the thromboxane synthetase inhibitor (E)-4-(1- imidazoylmethyl)cinnamic acid
-
The direct photoisomerization of (E)-4-(1-imidazoylmethyl)-cinnamic acid (IMC), a thromboxane synthetase inhibitor, to its (Z)-isomer at pH 2.0 was decelerated by β-cyclodextrin (β-CyD) and heptakis(2,6-di-O-methyl)-β- cyclodextrin (DM-β-CyD). The photostationary composition [(Z)-isomer:IMC ratio] was shifted in favor of IMC. These effects were much greater with DM- β-CyD than with the parent β-CyD. The quantum yield of the photoisomerization was significantly decreased by complex formation with β- CyDs, whereas the extinction coefficient of the guest was only slightly decreased. This situation was in sharp contrast to those observed in less polar solvents and suggests that the suppressing mechanism with β-CyD is different from that with less polar solvent systems. Spectroscopic studies (ultraviolet, circular dichroism, and nuclear magnetic resonance) indicated that IMC is tightly included in an axial mode in the cavity of DM-β-CyD and that the rotation of the photoreactive site is sterically hindered. The results suggest that the suppressing effect of β-CyDs on the photoisomerization of IMC results mainly from a steric origin.
- Hirayama,Utsuki,Uekama,Yamasaki,Harata
-
p. 817 - 822
(2007/10/02)
-
- Highly selective inhibitors of thromboxane synthetase. 1. Imidazole derivatives
-
The structure-activity relationships of imidazole derivatives as inhibitors of thromboxane (TX) synthetase were investigated. Introduction of various substituents (e.g., one or two methyl groups, a halogen atom, a methylidene group, unsaturated bonds, or a phenylene group) into the α position or other positions in the carboxy-bearing side chain of 1-(7-carboxyheptyl)imidazole was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum for the inhibitory potency on TX synthetase in the region of 8.5-9.0 A. Among the tested imidazole derivatives, 1-(7-carboxy-7-methyl-2-octynyl)imidazole, 4-[3-(1-imidazolyl)-propyl]benzoic acid, and (E)-4-(1-imidazolylmethyl)cinnamic acid and its α-methyl analogue showed the highest potency with an IC50 in the range of 10-8 to 10-9 M. Inhibition by these derivatives was highly selective for the TX synthetase, since other enzymes such as fatty acid cyclo-oxygenase and prostacyclin synthetase were not affected.
- Iizuka,Akahane,Momose,Nakazawa,Tanouchi,Kawamura,Ohyama,Kajiwara,Iguchi,Okada,Taniguchi,Miyamoto,Hayashi
-
p. 1139 - 1148
(2007/10/02)
-
- Imidazole derivative
-
Novel imidazole derivatives of the general formula (I): STR1 wherein Y is a carboxyl group, an alkoxycarbonyl group, a cyano group, a hydroxymethyl group, an aminomethyl group, a formyl group or a carbamoyl group, and A and B, which may be the same or different, each is a straight- or branched-chain alkylene or alkenylene group, and n and m, which may be the same or different, each is zero or 1, with the proviso that when A is methylene group or n is zero, m is 1; and pharmaceutically acceptable salts thereof. These compounds have a strong inhibitory effect on thromboxane synthetase from rabbit platelet microsomes, and are useful as therapeutically active agents for the treatment of inflammation, hypertension, thrombus, cerebral apoplexy and asthma.
- -
-
-