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WO2022198777A1 - Application d'un composé de triazole dans la préparation de médicaments antitumoraux - Google Patents

Application d'un composé de triazole dans la préparation de médicaments antitumoraux Download PDF

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Publication number
WO2022198777A1
WO2022198777A1 PCT/CN2021/095201 CN2021095201W WO2022198777A1 WO 2022198777 A1 WO2022198777 A1 WO 2022198777A1 CN 2021095201 W CN2021095201 W CN 2021095201W WO 2022198777 A1 WO2022198777 A1 WO 2022198777A1
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WO
WIPO (PCT)
Prior art keywords
application
preparation
cells
triazole compound
antitumor drugs
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2021/095201
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English (en)
Chinese (zh)
Inventor
李环球
汪维鹏
吕依昕
朱一凡
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Suzhou University
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Suzhou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Suzhou University filed Critical Suzhou University
Publication of WO2022198777A1 publication Critical patent/WO2022198777A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the invention belongs to the field of antitumor drugs, in particular to the application of a triazole compound in the preparation of antitumor drugs.
  • small molecule compounds have a wide range of potential applications as medicinal drugs and diagnostics. Especially in clinical anti-cancer, anti-tumor, etc., a large number of small molecule compounds have been successfully developed, sold and widely used in the prevention and treatment of various diseases. It has been widely used in many fields such as chemistry, medicine, biology and materials science.
  • Small chemical molecules can pass through the cell membrane and affect the expression and function of intracellular targets, and have a wide range of applications; in addition, small chemical molecules have good oral bioavailability after chemical modification. Better compliance; regardless of price or dosage form, the research on chemical small molecule drugs is more mature than biological drugs, and in contrast, it has good potential and market competitiveness. Therefore, it is of great significance to find new structural types of antitumor drugs.
  • the purpose of the present invention is to provide the application of a triazole compound in the preparation of antitumor drugs, and the small molecule compound has good inhibitory activity on multiple primary and transformed tumor cells.
  • the triazole compound is N-(5-benzothiazole-2-thiomethyl)-4 hydrogen-1,2,4 triazole-3-benzamide, and has the structure shown in formula I:
  • the pharmaceutically acceptable salts are hydrochloride, phosphate, sulfate, acetate, maleate, citrate, benzenesulfonate, toluenesulfonate, rich One or more of malate and tartrate.
  • the tumor includes, but is not limited to, colon cancer, stomach cancer, or lung cancer.
  • the present invention also provides the application of a triazole compound or a pharmaceutically acceptable salt thereof in the preparation of a drug for inhibiting tumor cells.
  • the tumor cells are colon cancer cells SW480, drug-resistant colon cancer cells SW620, gastric cancer cells SGC7901 or lung cancer cells A549.
  • the invention provides the application of a triazole compound or a pharmaceutically acceptable salt thereof in the preparation of an antitumor drug.
  • the present invention discovers for the first time that the triazole compound N-(5-benzothiazole-2-thiomethyl)-4hydro-1,2,4triazole-3-benzamide has antitumor activity, and has antitumor activity against many
  • the primary and transformed tumor cells have a good inhibitory effect and can be used as anti-tumor drugs.
  • Figure 1 shows the inhibitory activity of test compounds on colon cancer cell SW480 in vitro
  • Figure 2 shows the inhibitory activity of test compounds on drug-resistant colon cancer cells SW620 in vitro.
  • N-(5-benzothiazole-2-thiomethyl)-4 hydrogen-1,2,4 triazole-3-benzamide compound is prepared according to the following process:
  • N-(5-benzothiazole-2-thiomethyl)-4 hydrogen-1,2,4 triazole-3-benzamide compound used in the present invention is according to the document Shestakov, A.S.; Gusakova, N.V.; Verezhnikov, V.N.; Shikhaliev, Kh.S. Synthesis of triazolamines from cyanamides and hydrazides Izvestiya Vysshikh Uchebnykh Zavedenii, Khimiya i Khimicheskaya Tekhnologiya (2005), 48 (6), 126-129 The method is obtained.
  • the selected tumor cells include colon cancer cells SW480, drug-resistant colon cancer cells SW620, gastric cancer cells SGC7901, and lung cancer cells A549.
  • Cells in the logarithmic growth phase were taken, digested and counted, and the cell state was adjusted before plating.
  • the cells were seeded at a density of 3000 cells/well in a 96-well plate and placed in an incubator overnight. (Note: The outer circle is filled with PBS.) After 18 to 24 hours, the drug administration operation is carried out. Aspirate the cell culture medium and add a culture medium containing a certain concentration of the drug.
  • the experiment set blank group (solvent control group) and experimental group.
  • the drug concentrations in the experimental group were 1 ⁇ M, 5 ⁇ M, 20 ⁇ M, 50 ⁇ M, 100 ⁇ M, and 200 ⁇ M.
  • Three sub-wells were set in each group of experiments, the positive control was pentafluorouracil, and the method was the same as that of the test compound.
  • test compound N-(5-benzothiazole-2-thiomethyl)-4hydro-1,2,4triazole-3-benzamide has antitumor activity, and it has antitumor activity against many strains of progenitors. It has a good inhibitory effect on the development and transformation of tumor cells, and can be used as an anti-tumor drug.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une application d'un composé de triazole et d'un sel pharmaceutiquement acceptable de celui-ci dans la préparation de médicaments antitumoraux. Le composé triazole N-(5-benzothiazole-2-thiométhyle)-4H-1,2,4-triazole-3-benzamide a une activité antitumorale, a un bon effet inhibiteur sur une pluralité de souches de cellules tumorales primaires et transformées, et peut être utilisé pour la préparation de médicaments antitumoraux.
PCT/CN2021/095201 2021-03-22 2021-05-21 Application d'un composé de triazole dans la préparation de médicaments antitumoraux Ceased WO2022198777A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202110301156.3A CN112999221B (zh) 2021-03-22 2021-03-22 一种三氮唑类化合物在制备抗肿瘤药物中的应用
CN202110301156.3 2021-03-22

Publications (1)

Publication Number Publication Date
WO2022198777A1 true WO2022198777A1 (fr) 2022-09-29

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Application Number Title Priority Date Filing Date
PCT/CN2021/095201 Ceased WO2022198777A1 (fr) 2021-03-22 2021-05-21 Application d'un composé de triazole dans la préparation de médicaments antitumoraux

Country Status (2)

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CN (1) CN112999221B (fr)
WO (1) WO2022198777A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005097758A1 (fr) * 2004-03-26 2005-10-20 Amphora Discovery Corporation Composes et compositions a base de triazoles et leurs applications
CN102725281A (zh) * 2009-06-05 2012-10-10 奥斯陆大学医院公司 作为wtn通路抑制剂的氮杂茂类衍生物
CN106380465A (zh) * 2016-09-05 2017-02-08 郑州大学 含1，2，3‑三氮唑结构单元的2，4‑二取代喹唑啉类化合物及其制备方法和用途
CN108191781A (zh) * 2018-01-08 2018-06-22 浙江大学 取代三氮唑类衍生物及其在制备抗肿瘤转移药物中的应用
CN109456312A (zh) * 2018-10-29 2019-03-12 郑州大学 1,2,3-三氮唑类微管蛋白聚合抑制剂其合成方法和应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108653282B (zh) * 2018-06-28 2020-08-14 中国科学院昆明植物研究所 苯并噻唑类及苯并吡咯类化合物在制备抗肿瘤药物中的应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005097758A1 (fr) * 2004-03-26 2005-10-20 Amphora Discovery Corporation Composes et compositions a base de triazoles et leurs applications
CN102725281A (zh) * 2009-06-05 2012-10-10 奥斯陆大学医院公司 作为wtn通路抑制剂的氮杂茂类衍生物
CN106380465A (zh) * 2016-09-05 2017-02-08 郑州大学 含1，2，3‑三氮唑结构单元的2，4‑二取代喹唑啉类化合物及其制备方法和用途
CN108191781A (zh) * 2018-01-08 2018-06-22 浙江大学 取代三氮唑类衍生物及其在制备抗肿瘤转移药物中的应用
CN109456312A (zh) * 2018-10-29 2019-03-12 郑州大学 1,2,3-三氮唑类微管蛋白聚合抑制剂其合成方法和应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SHESTAKOV, A. S. ET AL.: "Synthesis of triazolamines from cyanamides and hydrazides.", IZVESTIYA VYSSHIKH UCHEBNYKH ZAVEDENII, KHIMIYA I KHIMICHESKAYA TEKHNOLOGIYA., vol. 48, no. 6, 31 December 2005 (2005-12-31), XP009159144 *

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CN112999221A (zh) 2021-06-22
CN112999221B (zh) 2022-04-12

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