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CN-121990896-A - Aryl ether compound and preparation method and application thereof

CN121990896ACN 121990896 ACN121990896 ACN 121990896ACN-121990896-A

Abstract

The invention relates to the technical field of medicines, relates to an aryl ether compound and a preparation method and application thereof, and in particular relates to an aryl ether compound and a preparation method and application thereof in preparation of antibacterial and antitumor drugs. The structure of the aryl ether compound is shown in the general formulas I-IV, wherein R 1 -R 31 and n are as defined in the claims and the specification. The invention also provides a composition of the aryl ether compound or the pharmaceutically acceptable salt thereof. The compound or the composition thereof has obvious antibacterial and antitumor activities, and can be used for preparing antibacterial medicines or antitumor medicines.

Inventors

  • WANG MINGZHONG
  • SONG XUN

Assignees

  • 深圳技术大学

Dates

Publication Date
20260508
Application Date
20241101

Claims (10)

  1. 1. Aryl ether compounds represented by general formulas I-IV or pharmaceutically acceptable salts thereof: Wherein, the R 1 is halogen, OH, trifluoromethanesulfonic acid group, cyano group, benzyloxy group, C1-C6 alkyl group, C1-C6 alkoxy group, C2-C6 alkenyl group; R 2 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; r 3 is H, benzyl, C1-C6 alkyl, C1-C6 alkoxy; R 4 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; R 5 is H or halogen; R 6 is C1-C6 alkyl, C1-C6 alkoxy; R 7 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; R 8 is OH, trifluoromethanesulfonic acid group, C2-C6 alkenyl group, benzyloxy group, C1-C6 alkyl group, C1-C6 alkoxy group; R 9 is H, OH, halogen, C1-C6 alkyl, C1-C6 alkoxy, benzyloxy, phenoxy; R 10 is H, benzyl, C1-C6 alkyl, C1-C6 alkoxy; R 11 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; r 12 is H, benzyl, tert-butyldimethylsilyl, C1-C6 alkyl, C1-C6 alkoxy; R 13 is H or halogen; R 14 is H, benzyl, C1-C6 alkyl, C1-C6 alkoxy; R 15 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; n is 0 to 10, preferably 0 to 5, more preferably 0 to 2; R 16 is halogen, OH, benzyloxy, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 alkenyl; r 17 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; r 18 is H, benzyl, C1-C6 alkyl, C1-C6 alkoxy; r 19 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; r 20 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; R 21 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; r 22 is H, benzyl, tert-butyldimethylsilyl, C1-C6 alkyl, C1-C6 alkoxy; R 23 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; R 24 is halogen, OH, amino, cyano, benzyloxy, phenoxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, methyl methylene ether; R 25 is H, OH, benzyl, C1-C6 alkyl, C1-C6 alkoxy; R 26 is H, OH, halogen, benzyloxy, C1-C6 alkyl, C1-C6 alkoxy; R 27 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; R 28 is H, CH 2 OCH 3 , C1-C6 alkyl, benzyl, C1-C6 alkoxy; R 29 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy; R 30 is H, halogen, OH, methyl methylene ether group, benzyloxy group, C1-C6 alkyl group, C1-C6 alkoxy group, dimethyl tertiary butyl silicon ether; r 31 is H, COR, OH, halogen, amino, cyano, benzyloxy, phenoxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl; r=h, OH, C1-C6 alkoxy, benzyloxy.
  2. 2. The aryl ether compound of claim 1 or a pharmaceutically acceptable salt thereof, Wherein, the R 1 is halogen, OH, trifluoromethanesulfonic acid group, cyano group, benzyloxy group, C1-C4 alkyl group, C1-C4 alkoxy group, C2-C4 alkenyl group; r 2 is H, cl, C1-C4 alkyl, C1-C4 alkoxy; r 3 is H, benzyl, C1-C4 alkyl, C1-C4 alkoxy; r 4 is H, cl, C1-C4 alkyl, C1-C4 alkoxy; R 5 is H, cl; r 6 is C1-C4 alkyl, C1-C4 alkoxy; r 7 is H, cl, C1-C4 alkyl, C1-C4 alkoxy; r 8 is OH, trifluoromethanesulfonic acid group, C2-C4 alkenyl group, benzyloxy group, C1-C4 alkyl group, C1-C4 alkoxy group; r 9 is H, OH, halogen, C1-C4 alkyl, C1-C4 alkoxy, benzyloxy, phenoxy; r 10 is H, benzyl, C1-C4 alkyl, C1-C4 alkoxy; R 11 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy; R 12 is H, benzyl, tert-butyldimethylsilyl, C1-C4 alkyl, C1-C4 alkoxy; R 13 is H or halogen; R 14 is H, benzyl, C1-C4 alkyl, C1-C4 alkoxy; r 15 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy; R 16 is halogen, OH, benzyloxy, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 alkenyl; r 17 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy; R 18 is H, benzyl, C1-C4 alkyl, C1-C4 alkoxy; r 19 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy; R 20 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy; R 21 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy; R 22 is H, benzyl, tert-butyldimethylsilyl, C1-C4 alkyl, C1-C4 alkoxy; R 23 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy; R 24 is halogen, OH, amino, cyano, benzyloxy, phenoxy, C1-C4 alkyl, C1-C4 alkoxy, C2-C6 alkenyl, methyl methylene ether; R 25 is H, OH, benzyl, C1-C4 alkyl, C1-C4 alkoxy; R 26 is H, OH, F, benzyloxy, C1-C4 alkyl, C1-C4 alkoxy; R 27 is H, cl, C1-C4 alkyl, C1-C4 alkoxy; R 28 is H, CH 2 OCH 3 , C1-C4 alkyl, benzyl, C1-C4 alkoxy; R 29 is H, cl, C1-C4 alkyl, C1-C4 alkoxy; R 30 is H, F, I, OH, methyl methylene ether, benzyloxy, C1-C4 alkyl, C1-C4 alkoxy, dimethyl tertiary butyl silyl ether; r 31 is H, COR, OH, halogen, amino, cyano, benzyloxy, phenoxy, C1-C4 alkyl, C1-C4 alkoxy, C2-C6 alkenyl; r=h, OH, C1-C4 alkoxy, benzyloxy.
  3. 3. The aryl ether compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
  4. 4. an intermediate for preparing the aryl ether compound of any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof:
  5. 5. a process for producing an aryl ether compound represented by the general formulae I to IV or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, Preparing a compound of a general formula II from an aromatic compound containing carboxylic acid and an aromatic compound containing alcohol under the action of dicyclohexylcarbodiimide and 4-dimethylaminopyridine; the compound of the general formula II firstly undergoes deprotection reaction, then undergoes ring closure under the catalysis of copper salt or palladium salt to form a compound of a seven-membered lactone ring, and the compound of the general formula I is further modified and derived; preparing a compound of a general formula III from aryl halides and phenol compounds under the catalysis of copper salts or palladium salts; the phenol compound is used as a raw material and reacts with halogenated hydrocarbon under the action of alkali to prepare the compound IV.
  6. 6. The process according to claim 5, wherein, The preparation scheme of the compound of formula II: The preparation scheme of the compound of the general formula I: The preparation scheme of the compound of formula III: the preparation scheme of the compound of formula IV: wherein R 1 -R 31 and n are as defined in claim 1.
  7. 7. A pharmaceutical composition comprising the aryl ether compound of any one of claims 1-3 or a pharmaceutically acceptable salt thereof.
  8. 8. Use of an aryl ether compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition according to claim 7 for the manufacture of an antibacterial agent, preferably an antifungal agent or an antibacterial agent.
  9. 9. Use of an aryl ether compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition according to claim 7 for the preparation of an anti-tumour agent, preferably lung cancer.
  10. 10. The use of the intermediate according to claim 4 for the preparation of an aryl ether compound or a pharmaceutically acceptable salt thereof.

Description

Aryl ether compound and preparation method and application thereof Technical Field The invention relates to the technical field of medicines, relates to an aryl ether compound and a preparation method and application thereof, and in particular relates to an aryl ether compound and a preparation method and application thereof in preparation of antibacterial and antitumor drugs. Background Aryl ether compounds are mainly derived from marine fungus Spiromastix sp (MCCC 3a 00308) strain, which is mainly distributed in sedimentary rocks of 2869 km or more in the south of the atlantic, and is difficult to collect. The content of the aryl ether compounds in the natural world is low (the content of partial compounds in fermentation liquor is lower than 0.5 milligram per liter), the quantity of the aryl ether compounds is low, no report is made on the artificial total synthesis preparation method of the aryl ether compounds, and no general method is available for synthesizing compounds with different substitution conditions. And the related report of the application of the derivative with the structure in the aspect of preparing antibacterial and antitumor drugs is not seen. Disclosure of Invention The technical problem solved by the invention is to overcome the defects of the prior art and provide a series of novel aryl ether compounds, wherein the aryl ether compounds have obvious antibacterial and antitumor activities. The invention is realized by the following technology: the invention provides aryl ether compounds represented by general formulas I-IV or pharmaceutically acceptable salts thereof: Wherein, the R 1 is halogen, OH, trifluoromethanesulfonic acid group, cyano group, benzyloxy group, C1-C6 alkyl group, C1-C6 alkoxy group, C2-C6 alkenyl group. R 2 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 3 is H, benzyl, C1-C6 alkyl, C1-C6 alkoxy. R 4 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 5 is H or halogen. R 6 is C1-C6 alkyl, C1-C6 alkoxy. R 7 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 8 is OH, trifluoromethanesulfonic acid group, C2-C6 alkenyl group, benzyloxy group, C1-C6 alkyl group, C1-C6 alkoxy group. R 9 is H, OH, halogen, C1-C6 alkyl, C1-C6 alkoxy, benzyloxy, phenoxy. R 10 is H, benzyl, C1-C6 alkyl, C1-C6 alkoxy. R 11 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 12 is H, benzyl, tert-butyldimethylsilyl, C1-C6 alkyl, C1-C6 alkoxy. R 13 is H or halogen. R 14 is H, benzyl, C1-C6 alkyl, C1-C6 alkoxy. R 15 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. N is 0 to 10, preferably 0 to 5, more preferably 0 to 2. R 16 is halogen, OH, benzyloxy, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 alkenyl. R 17 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 18 is H, benzyl, C1-C6 alkyl, C1-C6 alkoxy. R 19 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 20 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 21 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 22 is H, benzyl, tert-butyldimethylsilyl, C1-C6 alkyl, C1-C6 alkoxy. R 23 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 24 is halogen, OH, amino, cyano, benzyloxy, phenoxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, methyl methylene ether group. R 25 is H, OH, benzyl, C1-C6 alkyl, C1-C6 alkoxy. R 26 is H, OH, halogen, benzyloxy, C1-C6 alkyl, C1-C6 alkoxy. R 27 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 28 is H, CH 2OCH3, C1-C6 alkyl, benzyl, C1-C6 alkoxy. R 29 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy. R 30 is H, halogen, OH, methyl methylene ether group, benzyloxy group, C1-C6 alkyl group, C1-C6 alkoxy group, dimethyl tertiary butyl silicon ether. R 31 is H, COR (R=H, OH, C1-C6 alkoxy, benzyloxy), OH, halogen, amino, cyano, benzyloxy, phenoxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl. The present invention preferably provides the following aryl ether compounds or pharmaceutically acceptable salts thereof: R 1 is halogen, OH, trifluoromethanesulfonic acid group, cyano group, benzyloxy group, C1-C4 alkyl group, C1-C4 alkoxy group, C2-C4 alkenyl group. R 2 is H, cl, C1-C4 alkyl, C1-C4 alkoxy. R 3 is H, benzyl, C1-C4 alkyl, C1-C4 alkoxy. R 4 is H, cl, C1-C4 alkyl, C1-C4 alkoxy. R 5 is H, cl. R 6 is C1-C4 alkyl, C1-C4 alkoxy. R 7 is H, cl, C1-C4 alkyl, C1-C4 alkoxy. R 8 is OH, trifluoromethanesulfonic acid group, C2-C4 alkenyl group, benzyloxy group, C1-C4 alkyl group, C1-C4 alkoxy group. R 9 is H, OH, halogen, C1-C4 alkyl, C1-C4 alkoxy, benzyloxy, phenoxy. R 10 is H, benzyl, C1-C4 alkyl, C1-C4 alkoxy. R 11 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy. R 12 is H, benzyl, tert-butyldimethylsilyl, C1-C4 alkyl, C1-C4 alkoxy. R 13 is H or halogen. R 14 is H, benzyl, C1-C4 alkyl, C1-C4 alkoxy. R 15 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy. N is 0 to 10, preferably 0 to 5, more preferably 0 to 2. R 16 is halogen, OH, benzyloxy, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 alkenyl. R 17 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy. R 18 is H, benzyl, C1-C4 alkyl, C1-C4 alkoxy. R 19 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy. R 20 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy. R 21 is H, halogen, C1-C4 alkyl, C1-C4 alkoxy. R 22 is H, benzyl, tert