阅读说明：本技术 一种3-芳胺基喹喔啉-2-甲酰胺类衍生物及其制备方法和应用 (3-arylamino quinoxaline-2-formamide derivative and preparation method and application thereof ) 是由 苏桂发 陈南英 陆克 潘成学 袁静梅 于 2019-09-11 设计创作，主要内容包括：本发明一种3-芳胺基喹喔啉-2-甲酰胺类衍生物及其制备方法和应用,利用简便的方法合成了一种3-芳胺基喹喔啉-2-甲酰胺类衍生物,得率高,生产成本低,得到的3-芳胺基喹喔啉-2-甲酰胺类衍生物具有3-芳胺基喹喔啉-2-甲酰胺母核结构,其在体外及体内均显示良好的抗癌效果,可制成各种剂型的抗癌药物,具有很高的医学价值和广阔的市场前景。(The 3-arylamino quinoxaline-2-formamide derivative is synthesized by a simple method, has high yield and low production cost, has a 3-arylamino quinoxaline-2-formamide parent nucleus structure, shows good anticancer effect in vitro and in vivo, can be prepared into anticancer drugs of various formulations, and has high medical value and wide market prospect.)

1. A3-arylamino quinoxaline-2-formamide derivative is characterized in that the structural formula of the derivative is shown as a formula I,

wherein R is¹Is H or halogen or alkyl or alkoxy or haloalkyl; r is amino or alkylamino or a nitrogen-containing heterocycle; n =2 or 3.

2. A 3-arylaminoquinoxaline-2-carboxamide derivative according to claim 1, characterized in that the structural formula of the derivative is as follows:

3. a process for preparing a 3-arylaminoquinoxaline-2-carboxamide derivative according to claim 1, characterized in that it comprises the following steps:

(1) preparation of compound 4: adding the compound 2, the compound 3 and ethanol into a reaction container in sequence, heating under the protection of nitrogen, stirring for reaction, cooling to room temperature after the reaction is finished, performing suction filtration, taking filter residue, washing and drying to obtain a compound 4;

(2) preparing a target product 6: adding the compound 4, the compound 5 and ethanol into a reaction vessel in sequence, heating and stirring for reaction under the protection of nitrogen, cooling to room temperature after the reaction is finished, removing the solvent, and purifying to obtain a target product 6;

the structural formula of the compound 2 is as follows:

4. the method according to claim 3, wherein the temperature of the stirring reaction in the step (1) is 75 ℃ to 85 ℃.

5. The method according to claim 3, wherein the stirring reaction time in step (1) is 21 to 23 hours.

6. The method according to claim 3, wherein the temperature of the stirring reaction in the step (2) is 75 ℃ to 85 ℃.

7. The method according to claim 3, wherein the stirring reaction time in step (2) is 2.5 to 3.5 hours.

8. The use of a 3-arylaminoquinoxaline-2-carboxamide derivative according to claim 1 for the preparation of an anti-tumor medicament.

9. The use of a 3-arylaminoquinoxaline-2-carboxamide derivative according to claim 1 for the preparation of a medicament against gastric cancer.

10. The use of a 3-arylaminoquinoxaline-2-carboxamide derivative according to claim 1 for the preparation of a medicament against liver cancer.

Technical Field

The invention relates to the field of medicinal chemistry, in particular to a 3-arylamino quinoxaline-2-formamide derivative and a preparation method and application thereof.

Background

The tumor is a common disease and frequently encountered disease, wherein malignant tumor has become a main disease threatening human health, and the morbidity and mortality of the malignant tumor are the first of all diseases. In 2 months of 2017, the national cancer center issues the latest Chinese cancer data, and the data shows that about 1 million people in China can diagnose cancer every day, namely about 7 people per minute. Quinoxaline is a very important nitrogen-containing heterocyclic ring and a very important dominant structural unit in medicinal chemistry, and the derivative thereof has wide biological activities such as cancer resistance, anti-inflammation, antibiosis, malaria resistance and the like, and has very wide application in the aspects of medicines, pesticides, photoelectric materials and the like. Therefore, designing new bioactive compounds by using quinoxaline as a basic skeleton as a dominant structural unit is always a hot research field of medicinal chemistry.

The 3-arylamino quinoxaline-2-formamide derivatives have various biological activities, have wide application, are easy to cause side reaction in the synthesis process, have low yield and have very limited synthesis method.

Disclosure of Invention

The invention aims to: aiming at the problems, the invention provides the 3-arylamino quinoxaline-2-formamide derivative with high yield and good anticancer effect, and the preparation method and the application thereof.

The invention is realized by the following technical scheme:

the present invention provides: a3-arylamino quinoxaline-2-formamide derivative has a structural formula shown in a formula I,

wherein R is¹Is H or halogen or alkyl or alkoxy or haloalkyl; r is amino or alkylamino or a nitrogen-containing heterocycle; n is 2 or 3.

Further, the structural formula of the derivative is shown as follows:

the invention also provides a method for preparing the 3-arylamino quinoxaline-2-formamide derivatives, which comprises the following steps:

(1) preparation of compound 4: adding the compound 2, the compound 3 and ethanol into a reaction container in sequence, heating under the protection of nitrogen, stirring for reaction, cooling to room temperature after the reaction is finished, performing suction filtration, taking filter residue, washing and drying to obtain a compound 4;

(2) preparing a target product 6: adding the compound 4, the compound 5 and ethanol into a reaction vessel in sequence, heating and stirring for reaction under the protection of nitrogen, cooling to room temperature after the reaction is finished, removing the solvent, and purifying to obtain a target product 6;

the structural formula of the compound 2 is as follows:the structural formula of compound 3 is:the structural formula of compound 4 is:the structural formula of compound 5 is:

the structural formula of compound 6 is:

further, in the step (1), the temperature for stirring the reaction is 75-85 ℃.

Further, in the step (1), the stirring reaction time is 21-23 h.

Further, in the step (2), the temperature for stirring the reaction is 75-85 ℃.

Furthermore, in the step (2), the stirring reaction time is 2.5-3.5 h.

The invention also provides: an application of 3-arylamino quinoxaline-2-formamide derivatives in preparing antineoplastic medicines.

The invention also provides: an application of 3-arylamino quinoxaline-2-formamide derivatives in preparing anti-gastric cancer drugs.

The invention also provides: an application of 3-arylamino quinoxaline-2-formamide derivatives in preparing anti-liver cancer drugs.

The preparation route of the 3-arylamino quinoxaline-2-formamide derivative is as follows:

the invention synthesizes the 3-arylamino quinoxaline-2-formamide derivative by a simple method, has high yield and low production cost, and the obtained 3-arylamino quinoxaline-2-formamide derivative has a 3-arylamino quinoxaline-2-formamide parent nucleus structure, shows good anticancer effect in vitro and in vivo, can be prepared into anticancer drugs of various formulations, and has high medical value and wide market prospect.

Detailed Description

Any feature disclosed in this specification (including any accompanying claims, abstract) may be replaced by alternative features serving equivalent or similar purposes, unless expressly stated otherwise. That is, unless expressly stated otherwise, each feature is only an example of a generic series of equivalent or similar features.