Uses of sesquiterpene lactone compounds and their derivatives in drugs preparation

Patent metadata

Field	Value
Publication number	US-2016367525-A1
Application number	US-201315110592-A
Country	US
Kind code	A1
Filing date	Jul 15, 2013
Priority date	Jul 15, 2013
Publication date	Dec 22, 2016
Grant date	—

Abstract

The present invention relates to the uses of sesquiterpene lactone compounds and their derivatives in preparing drugs. It belongs to the field of drug technology, specifically relates to the uses of the compounds of Formula (I) in preparing the drugs, especially the uses in preparing the drugs to treat rheumatoid arthritis and treat cancers through inhibiting cancer stem cells.

First claim

What is claimed is:

1 . Uses of the compounds of Formula (I) in preparing drugs.

where: R 1 and R 2 form double bond together or R 1 is hydrogen or deuterium, R 2 is

and the pharmaceutically acceptable salts formed by it and inorganic acid or organic acid including the quaternary ammonium salts formed with R 5 Z, where R 3 and R 4 can be the same or different selected from hydrogen, alkyl, cycloalkyl, hydroxy-substituting alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic, trifluoromethyl, polyfluoroalkyl, nitrile group, cyanomethyl, acyl, carbamoyl, sulfonyl, sulfonamide or aryloxyalkyl; R 3 , R 4 and N atom form cyclic structure which is preferably 3-member to 9-member ring, where one or more positions on the ring structure can be replaced by the substituent group including hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, arylalkenyl, arylalkynyl or heterocyclic; Z is fluorine, chlorine, bromine, iodine, toluene-p-sulfonate group, mesylate group, benzenesulfonate group or trifluoromethanesulfonate group; R 5 is alkayl, cycloalkyl, hydroxy-substituting alkyl, alkenyl, alkynyl, aryl, heterocyclic, aryl-substituting alkyl, arylalkenyl, arylalkynyl, cyano methyl, alkoxy-substituting alkyl or aryloxy substituting alkyl. Inorganic or organic acid can be hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, carbonic acid, boric acid, selenious acid, phosphomolybdic acid, phosphorous acid, sulfurous acid, citric acid, maleic acid, D-malic acid, L-malic acid, DL-malic acid, L-lactic acid, D-lactic acid, DL-lactic acid, oxalic acid, methanesulfonic acid, acid, oleic acid, lauric acid, p-toluenesulfonic, 1-naphthalenesulfonic acid, 2-naphthalenesulfonic acid, phthalic acid, tartaric acid, malonic acid, succinic acid, fumaric acid, glycolic acid, a thiol acid, glycine, sarcosine, sulfonic acid, nicotinic acid, picoline acid, isonicotinic, dichloroacetic acid, benzoic acid or substituted benzoic acid. Or R 2 is

where X thereof is O or S, R 6 is hydrogen, alkyl, cycloalkyl, hydroxy-substituting alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, arylalkenyl, arylalkynyl, heterocyclic, trifluoromethyl, polyfluoroalkyl, nitrile group, cyanomethyl, acyl, carbamoyl, sulfonyl, sulfonamide or aryloxyalkyl.
If there is no the bond - - - between R 7 and R 8 , R 7 and R 8 will form double bond together or R 7 is methyl, R 8 is hydroxyl or OCOR 9 where R 9 thereof is alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic.
If the bond - - - between R 7 and R 8 is single bond, R 7 ═R=methylene.
R 10 is hydrogen or R 10 and R 8 form single bond.
R 11 is hydrogen or R 11 and R 13 form single bond or epoxy bond.
If there is no bond - - - between R 12 and R 13 , R 12 and R 13 will form double bond together or R 12 is hydroxyl or R 14 , where R 14 thereof is alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, R 13 is methyl.
If the bond - - - between R 12 and R 13 is single bond, R 12 ═R 13 =methylene.

2 . According to claim 1 , the structural formula (I) is preferably:

3 . The uses of the compound(s) according to any claim of claim 1 to claim 2 in preparing drugs to treat rheumatoid arthritis.

4 . The uses of the compound(s) according to any claim of claim 1 to claim 2 in preparing adjuvant drugs to treat rheumatoid arthritis.

5 . The uses of the compound(s) according to any claim of claim 1 to claim 2 in preparing drugs to treat cancers through inhibiting cancer stem cells, where the cancers thereof are preferably acute myeloid leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, skin cancer, breast cancer, ovarian cancer, brain tumor, prostate cancer, head and neck squamous cell carcinoma, laryngeal cancer, pancreatic cancer, retinoblastoma, children hepatoblastoma, liver cancer, malignant melanoma, colorectal cancer, colon cancer, glioma, gastrointestinal tumor, nasopharyngeal carcinoma, brain glioma, gastric cancer, lung cancer and lung cancer.

6 . The uses of any compound according to claim 1 to claim 2 in preparing the adjuvant drugs to treat cancers through inhibiting cancer stem cells, where the cancers thereof are preferably acute myeloid leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, skin cancer, breast cancer, ovarian cancer, brain tumor, prostate cancer, head and neck squamous cell carcinoma, laryngeal cancer, pancreatic cancer, retinoblastoma, children hepatoblastoma, liver cancer, malignant melanoma, colorectal cancer, colon cancer, glioma, gastrointestinal tumor, nasopharyngeal carcinoma, brain glioma, gastric cancer, lung cancer and lung cancer.

7 . A pharmaceutical composition to treat rheumatoid arthritis, where said pharmaceutical composition comprises at least one compound according to any claim from claim 1 or claim 2 as the active component and a pharmaceutically acceptable carrier or other compound(s) to treat rheumatoid arthritis.

8 . A pharmaceutical composition to treat cancers through inhibiting cancer stem cells, where said pharmaceutical composition comprises at least one compound according to any claim from claim 1 to claim 2 as the active and a pharmaceutically acceptable carrier or other compound(s) to treat cancers through inhibiting cancer stem cells component and the cancers thereof are preferably acute myeloid leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, skin cancer, breast cancer, ovarian cancer, brain tumor, prostate cancer, head and neck squamous cell carcinoma, laryngeal cancer, pancreatic cancer, retinoblastoma, children hepatoblastoma, liver cancer, malignant melanoma, colorectal cancer, colon cancer, glioma, gastrointestinal tumor, nasopharyngeal carcinoma, brain glioma, gastric cancer, lung cancer and lung cancer.

Assignees

• Accendatech
• Univ Nankai

Inventors

• Chen Yue
• Zhang Quan
• Long Jing
• Ma Weiwei
• Zhai Jiadai
• Yang Xiudong
• Fan Hongxia
• Ding Yahui
• Wang Liang
• Han Bin
• Ma Xiaoyan
• Zhang Haoliang
• Qiu Chuanjiang

Classifications

• A61K31/4525

  containing a five-membered ring with oxygen as a ring hetero atom · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D493/04

  Ortho-condensed systems · CPC title

• C07D307/93

  condensed with a ring other than six-membered · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title