Title:
14-CHLORO-β-ELEMENE NITRIC OXIDE DONOR TYPE DERIVATIVE, PREPARATION AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/061095
Kind Code:
A1
Abstract:
The present invention relates to the field of medicinal chemistry. Disclosed in the present invention are a 14-chloro-β-elemene nitric oxide donor type derivative, preparation and application thereof in preparing an antitumor drug. The 14-chloro-β-elemene nitric oxide donor type derivative has a general formula as shown in formula (I). In the formula (I), R1 is a straight chain or cyclic alcoholamine structure containing nitrogen and oxygen atoms; R2 and R3 are independently selected from C1-10 chain alkyl, C3-12 cycloalkyl, C6-12 aryl, five- to ten-membered cycloheteroaryl, C2-10 alkenyl, C2-10 alkynyl or C2-10 alkoxy. The derivative in the present invention is superior to a conventional β-elemene nitric oxide donor type derivative in terms of a design policy, an alcoholamine structure capable of improving the in vivo antitumor activity is introduced as a connecting arm, the in vivo stability is improved, and the derivative has good therapeutic activity on malignant brain glioma clinically lacking an effective therapeutic drug.
Inventors:
XIE TIAN (CN)
BAI RENREN (CN)
YE XIANGYANG (CN)
ZHU JUNLONG (CN)
BAI ZIQIANG (CN)
BAI RENREN (CN)
YE XIANGYANG (CN)
ZHU JUNLONG (CN)
BAI ZIQIANG (CN)
Application Number:
PCT/CN2022/116672
Publication Date:
April 20, 2023
Filing Date:
September 02, 2022
Export Citation:
Assignee:
UNIV HANGZHOU NORMAL (CN)
International Classes:
C07D271/08; A61K31/4245; A61P35/00; C07D413/12
Foreign References:
| CN113801073A | 2021-12-17 | |||
| CN106866572A | 2017-06-20 | |||
| CN110627615A | 2019-12-31 | |||
| CN101538234A | 2009-09-23 | |||
| CN103848793A | 2014-06-11 | |||
| CN104130124A | 2014-11-05 | |||
| CN201710066664A | 2017-02-07 |
Other References:
BAI RENREN, ZHU JUNLONG, BAI ZIQIANG, MAO QING, ZHANG YINGQIAN, HUI ZI, LUO XINYU, YE XIANG-YANG, XIE TIAN: "Second generation β-elemene nitric oxide derivatives with reasonable linkers: potential hybrids against malignant brain glioma", JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, INFORMA HEALTHCARE, GB, vol. 37, no. 1, 31 December 2022 (2022-12-31), GB , pages 379 - 385, XP093057984, ISSN: 1475-6366, DOI: 10.1080/14756366.2021.2016734
JIA, WEIMIN ET AL.: "Synthesis of the Antitumor β-Elemene Derivatives", CHINESE JOURNAL OF ORGANIC CHEMISTRY, vol. 11, no. 6, 31 December 1991 (1991-12-31), CN , pages 608 - 610, XP009545421, ISSN: 0253-2786
ZOU, ZHIHONG ET AL.: "Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents.", BIOORG. MED. CHEM. LETT., vol. 21, no. 19, 29 July 2011 (2011-07-29), XP028286398, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2011.07.077
CHEN, JICHAO ET AL.: "Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway.", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 135, 20 April 2017 (2017-04-20), XP085047554, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2017.04.045
JIA, WEIMIN ET AL.: "Synthesis of the Antitumor β-Elemene Derivatives", CHINESE JOURNAL OF ORGANIC CHEMISTRY, vol. 11, no. 6, 31 December 1991 (1991-12-31), CN , pages 608 - 610, XP009545421, ISSN: 0253-2786
ZOU, ZHIHONG ET AL.: "Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents.", BIOORG. MED. CHEM. LETT., vol. 21, no. 19, 29 July 2011 (2011-07-29), XP028286398, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2011.07.077
CHEN, JICHAO ET AL.: "Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway.", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 135, 20 April 2017 (2017-04-20), XP085047554, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2017.04.045
Attorney, Agent or Firm:
BEIJING GAOWO LAW FIRM (CN)
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