CN-122010964-A - 4-Hydroxycoumarin derivative X77 and application thereof in preparation of medicines for treating or preventing carp herpesvirus infection

Abstract

The invention belongs to the field of aquatic virus medicaments, and discloses a 4-hydroxycoumarin derivative X77 and application thereof in preparing a medicament for treating or preventing carp herpesvirus infection. The applicant newly synthesizes a novel compound 4-hydroxycoumarin derivative X77 which has the effects of resisting the carp herpesvirus, in particular to the carp herpesvirus II and the koi herpesvirus in vivo and in vitro, has small toxic and side effects on normal cells, is a novel compound with small side effects and has the effect of resisting the carp herpesvirus, and lays a foundation for the drug development of the carp herpesvirus in the future.

Inventors

• ZHOU YONG
• JIANG NAN
• XUE MINGYANG
• XU CHEN
• HUANG ZHENYU
• MENG YAN
• FAN YUDING

Assignees

• 中国水产科学研究院长江水产研究所

Dates

Publication Date

20260512

Application Date

20260127

Claims (8)

1. 1. An artificially synthesized 4-hydroxycoumarin derivative X77 has the structural formula: 。
2. 2. a process for the preparation of the 4-hydroxycoumarin derivative X77 according to claim 1, comprising the steps of: 4-hydroxycoumarin, thiourea and acetamidobenzaldehyde are subjected to reflux reaction under stirring by taking ethanol-water as a solvent under the condition of taking piperidine and glacial acetic acid as catalysts, and the crude product is purified by silica gel column chromatography, so that the preparation method is provided.
3. 3. The process of claim 2, wherein 2.0 mmol of 4-hydroxycoumarin, 2.4 mmol thiourine and 2.0 mmol acetamidobenzaldehyde are put into a mixed solvent of ethanol and water in a volume ratio of 9:1, 0.1 mmol piperidine and 0.05 mmol glacial acetic acid are added as catalysts, the mixture is stirred and refluxed at 60 ℃ for 6 hours, the mixture is cooled to room temperature after the reaction, water is added to separate out solids, the solids are washed with dilute ethanol and water in sequence after filtration, and the crude product is eluted and purified by petroleum ether/ethyl acetate gradient after filtration.
4. 4. A compound preparation containing 4-hydroxycoumarin derivative X77.
5. 5. Use of the 4-hydroxycoumarin derivative X77 according to claim 1, a pharmaceutically acceptable salt thereof or the complex formulation according to claim 4 for the preparation of a medicament for the treatment or prophylaxis of herpes virus infection of carp.
6. 6. Use of the 4-hydroxycoumarin derivative X77 according to claim 1, a pharmaceutically acceptable salt thereof or the complex formulation according to claim 4 for the in vitro non-therapeutic inhibition of herpes virus of carp.
7. 7. The use according to claim 5 or 6, wherein the cyprinid herpesvirus comprises cyprinid herpesvirus type II (Cyprinid herpesvirus II) or/and Koi herpesvirus (Koi hepesvirus).
8. 8. Use of the 4-hydroxycoumarin derivative X77 according to claim 1, a pharmaceutically acceptable salt thereof or the complex formulation according to claim 4 for the preparation of a carp or crucian carp feed additive.

Description

4-Hydroxycoumarin derivative X77 and application thereof in preparation of medicines for treating or preventing carp herpesvirus infection Technical Field The invention belongs to the field of aquatic virus medicaments, and particularly relates to a 4-hydroxycoumarin derivative X77 and application thereof in preparing a medicament for treating or preventing carp herpesvirus infection. Background The carp herpesvirus (Cyprinid herpesvirus) is a large DNA virus with a diameter of about 80-100nm, has a capsule membrane, belongs to the family of the herpesviridae (Alloherpesvirus), and mainly infects fishes. The cyprinus carpio herpesvirus I is divided into 3 types, namely cyprinus carpio herpesvirus I with low mortality, cyprinus carpio herpesvirus II (also known as CyHV-2) mainly infects crucian carpio and goldfish with high mortality, cyprinus carpio herpesvirus III (also known as KHV) mainly senses cyprinus carpio and has high mortality. The cyprinid herpesvirus can be horizontally transmitted, has strong infectivity and high transmission speed. At present, the prevention and control of the carp herpesvirus is in a starting stage, and the prevention and control measures are still mainly prevention. Therefore, the development of the novel drug of the carp herpesvirus has positive significance and has obvious advantages for preventing the carp herpesvirus diseases which continuously occur in the aquaculture process. Coumarin compounds widely exist in natural products and bioactive drug molecules, have good photochemical stability and pharmacological activity, and are widely applied to preparations such as anticoagulants, antitumor drugs, antibacterial and anti-inflammatory agents and the like. Researches show that the coumarin derivative-esculin has antibacterial activity against colibacillus and the like, while the other coumarin derivative-Huang Tansu has antibacterial activity against gram-positive bacteria. The newly synthesized X77 is a member of a 4-hydroxycoumarin compound and has the function of resisting the carp herpesvirus. Disclosure of Invention The invention aims to provide a 4-hydroxycoumarin derivative X77, wherein the structural formula of X77 is as follows: 。 The invention also aims at providing the application of the 4-hydroxycoumarin derivative X77 in preparing a medicament for treating or preventing the carp herpesvirus infection. In order to achieve the above object, the present invention adopts the following technical measures: a4-hydroxycoumarin derivative X77 has a molecular formula of C 20H17N3O5 S, a molecular weight of 423.44 and a structural formula: 。 the preparation method of the 4-hydroxycoumarin derivative X77 comprises the following steps: 4-hydroxycoumarin, thiourea and acetamidobenzaldehyde are subjected to reflux reaction under stirring by taking ethanol-water as a solvent under the condition of taking piperidine and glacial acetic acid as catalysts, and the crude product is purified by silica gel column chromatography, so that the preparation method is provided. The steps are preferably carried out by placing 2.0 mmol 4-hydroxycoumarin, 2.4 mmol thiourine and 2.0 mmol acetamidobenzaldehyde into ethanol-water mixed solvent with volume ratio of 9:1, adding 0.1 mmol piperidine and 0.05 mmol glacial acetic acid as catalyst, stirring and refluxing at 60 ℃ for 6 hours, cooling to room temperature after reaction, adding water to separate out solid, filtering, washing with diluted ethanol and water sequentially, and gradient eluting and purifying crude product by petroleum ether/ethyl acetate after filtering. The protection scope of the invention also comprises: A compound preparation containing 4-hydroxycoumarin derivative X77. The application of the 4-hydroxycoumarin derivative X77, the pharmaceutically acceptable salt thereof or the compound preparation containing the 4-hydroxycoumarin derivative X77 in preparing medicines for treating or preventing the herpes virus infection of the carp. The application of the 4-hydroxycoumarin derivative X77, the pharmaceutically acceptable salt thereof or the compound preparation containing the 4-hydroxycoumarin derivative X77 in the in-vitro non-therapeutic inhibition of the carp herpesvirus. For the above application, preferably, the cyprinid herpesvirus comprises cyprinid herpesvirus type II (Cyprinid herpesvirus II, cyHV-2) or/and Koi Herpesvirus (KHV). Application of 4-hydroxycoumarin derivative X77, pharmaceutically acceptable salt thereof or compound preparation containing 4-hydroxycoumarin derivative X77 in preparing feed additive for carp or crucian carp. Compared with the prior art, the invention has the advantages that: According to the invention, the 4-hydroxycoumarin derivative X77 is synthesized for the first time, and verified that the derivative has a good inhibiting effect on the cyprinoid herpesvirus, has small toxic and side effects on normal cells, is a novel compound with small side effects and has the effect of resisti