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二苯并呋喃类化合物的设计合成及血管生成抑制作用 被引量:2

Design,synthesis and antiangiogenesis activity of dibenzofuran derivatives
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摘要 目的寻找具有抗血管生成作用的二苯并呋喃类化合物并探讨其初步构效关系。方法以苯酚类化合物、1,3-环己二烯为原料在对甲苯磺酸的催化下反应得到烷基化产物(2-环己烯基)-苯酚类化合物2a^2 e和环合产物六氢二苯并呋喃类化合物3a^3 e;2a^2 e在二(氰基苯)二氯化钯作用下环合得到1,2,3,4-四氢二苯并呋喃类化合物4a^4 e。以HUVEC、A549、Bel-7402和MCF-7为测试靶细胞,采用MTT法对目标化合物进行体外抑制内皮细胞和肿瘤细胞增殖的活性筛选。结果共合成了10个目标化合物,其结构经1H-NMR、13C-NMR、M S谱确证,3b^3 e和4b^4 e为新化合物。其中,化合物4 c、4 e对HUVEC具有良好的抑制作用并且对HUVEC具有显著的选择性。结论苯环上的羟基、烷基取代以及它们的取代位置对抑制HUVEC细胞增殖有重要影响;[4a,9a]的碳碳双键可能对化合物抑制HUVEC增殖有一定的提高作用。 Aim To discover dibenzofuran derivatives as angiogenesis inhibitors and to investigate their preliminary structure-activity relationship(SAR).Methods(Cyclohexen-2-yl)phenol derivatives of 2a-2e and hexahydrodibenzofuran derivatives of 3a-3e were synthesized by the reaction of phenols with activated 1,3-cyclohexadiene catalyzed by TsOH·H2O.1,2,3,4-Tetrahydrodibenzofuran derivatives of 4a-4e were afforded through intramolecular cyclization and dehydrogenation of(cyclohexen-2-yl)phenol derivatives of 2a-2e by the application of stoichiometric dichloro-bis(benzonitrile) palladium(Ⅱ).All compounds were tested by MTT method against the proliferation of HUVEC,A549,Bel-7402 and MCF-7.Results Ten target compounds were synthesized and determined by ^1H-NMR,^13C-NMR,MS,and compounds 3b-3e and 4b-4e are new compounds.Compounds 4c and 4e exhibited good inhibitory activity and remarkable selectivity to HUVEC proliferation.Conclusion Phenolic group and alkyl substitutents and their occupied positions are important for their inhibitory activity to HUVEC proliferation.It is possible that introduction of double bond can enhance anti-HUVEC proliferation activity.
出处 《中国药物化学杂志》 CAS CSCD 2010年第3期166-170,175,共6页 Chinese Journal of Medicinal Chemistry
基金 中国科学院知识创新项目(KSCX-2-YW-R-22) 国家自然科学基金资助项目(30973621)
关键词 二苯并呋喃 HUVEC 血管生成作用 构效关系 dibenzofuran HUVEC angiogenesis SAR
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  • 1CARMELIET P, JAIN R K. Angiogenesis in cancer and other diseases [ J]. Nature, 2000,407 ( 6801 ) : 249 - 257.
  • 2APERS S, PAPER D, BURGERMEISTER J, et al. Antiangiogenic activity of synthetic dihydrobenzofuran lignans[ J]. J Nat Prod,2002,65 (5) :718 -720.
  • 3HUR J M, SHIM J S, JUNG H J, et al. Cryptotanshinone but not tanshinone HA inhibits angiogenesis in vitro [ J ]. Exp Mol Meal,2005,37 (2) : 133 - 137.
  • 4OGURA H,NAKANISHI-UEDA N,UEDA T,et al. Effect of a dihydrobenzofuran derivative on lipid hydroperoxide-induced rabbit corneal neovascularization [ J ]. J Pharmacol Sci,2007,103 (2) :234 - 240.
  • 5SAIGO M, UEO M, KAMETAKA S, et al. Attenuation of cataract progression by A-3922, a dihydrobenzofuran derivative, in streptozotocin-induced diabetic rats [J]. Biol Pharm Bull, 2008, 31 (10) : 1959 - 1963.
  • 6CHEN Y ,CHEN S ,LU X,et al. Synthesis, discovery and preliminary SAR study of benzofuran derivatives as angiogenesis inhibitors [ J ]. Bioorg Med Chem Lett,2009,19(7) : 1851 - 1854.
  • 7LIU X,OU Y Y,CHEN S P,et al. Synthesis and inhibitory evaluation of cyclohexen-2-yl- and cyclohexyl-substituted phenols and quinones to endothelial cell and cancer cells[ Jl. Eur J Med Chem,2010,45 (6) :2147 -2153.
  • 8LEO E A, DELGADO J, DOMINGO L R, et al. Photogeneration of o-quinone methides from o-cycloalkenylphenols [ J]. J Org Chem,2003,68 ( 25 ) :9643 - 9647.
  • 9GRANT V H,LIU B. Iridium( III)-catalyzed tandem Claisen rearrangement intramolecular hydroaryloxyla- tion of aryl allyl ethers to form dihydrobenzofurans [ J ]. Tetrahedron Lett, 2005,46 ( 8 ) : 1237 - 1239.
  • 10HOSOKAWA T,OHKATA H,MORITANI. Intramolecular oxypalladation. Cyclization reaction of 2- allylphenols with palladium salts[J]. Bull Chem Soc Jpn, 1975,48 (5) : 1533 - 1536.

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