CN115583978B - 一种用于抑制隐球菌的吩嗪类钌(ⅱ)配合物六氟磷酸盐及其制备方法和应用 - Google Patents
一种用于抑制隐球菌的吩嗪类钌(ⅱ)配合物六氟磷酸盐及其制备方法和应用 Download PDFInfo
- Publication number
- CN115583978B CN115583978B CN202211191586.5A CN202211191586A CN115583978B CN 115583978 B CN115583978 B CN 115583978B CN 202211191586 A CN202211191586 A CN 202211191586A CN 115583978 B CN115583978 B CN 115583978B
- Authority
- CN
- China
- Prior art keywords
- ruthenium
- phenazine
- complex
- dppz
- preparation
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- -1 hexafluorophosphate Chemical compound 0.000 title claims abstract description 36
- VKCPLYYOSXEBJS-UHFFFAOYSA-N [Ru+2].C1=CC=CC2=NC3=CC=CC=C3N=C12 Chemical compound [Ru+2].C1=CC=CC2=NC3=CC=CC=C3N=C12 VKCPLYYOSXEBJS-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 241001337994 Cryptococcus <scale insect> Species 0.000 title claims abstract description 23
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 20
- 201000007336 Cryptococcosis Diseases 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 10
- 241000221204 Cryptococcus neoformans Species 0.000 claims abstract description 8
- 241000649026 Cryptococcus neoformans var. grubii H99 Species 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 3
- 239000003446 ligand Substances 0.000 abstract description 22
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 abstract description 9
- 150000003839 salts Chemical class 0.000 abstract description 9
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 abstract description 8
- 208000031984 bilateral perisylvian X-linked polymicrogyria Diseases 0.000 abstract description 8
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 6
- 230000000843 anti-fungal effect Effects 0.000 abstract description 4
- 229940121375 antifungal agent Drugs 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003937 drug carrier Substances 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 229910021645 metal ion Inorganic materials 0.000 abstract description 2
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 27
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 21
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 19
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 16
- 239000002243 precursor Substances 0.000 description 16
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 12
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 6
- 230000008014 freezing Effects 0.000 description 6
- 238000007710 freezing Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- KCALAFIVPCAXJI-UHFFFAOYSA-N 1,10-phenanthroline-5,6-dione Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CN=C3C2=N1 KCALAFIVPCAXJI-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- AXNUJYHFQHQZBE-UHFFFAOYSA-N 3-methylbenzene-1,2-diamine Chemical compound CC1=CC=CC(N)=C1N AXNUJYHFQHQZBE-UHFFFAOYSA-N 0.000 description 2
- XSZYBMMYQCYIPC-UHFFFAOYSA-N 4,5-dimethyl-1,2-phenylenediamine Chemical compound CC1=CC(N)=C(N)C=C1C XSZYBMMYQCYIPC-UHFFFAOYSA-N 0.000 description 2
- BXIXXXYDDJVHDL-UHFFFAOYSA-N 4-Chloro-ortho-phenylenediamine Chemical compound NC1=CC=C(Cl)C=C1N BXIXXXYDDJVHDL-UHFFFAOYSA-N 0.000 description 2
- BSMPRJISGCTCDC-UHFFFAOYSA-N 4-chloro-5-fluorobenzene-1,2-diamine Chemical compound NC1=CC(F)=C(Cl)C=C1N BSMPRJISGCTCDC-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 208000037026 Invasive Fungal Infections Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 244000053095 fungal pathogen Species 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012984 biological imaging Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000002815 broth microdilution Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 229960004884 fluconazole Drugs 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 150000003303 ruthenium Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
Abstract
本发明公开了一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐及其制备方法和应用,本发明中的盐以钌金属离子为核心,以1,10‑菲啰啉或联吡啶及其衍生物为骨架配体,以DPPZ‑F,Cl、DPPZ‑Cl、DPPZ‑Me和BPPX为结合配体,其性质稳定,对新生隐球菌具有良好的抗菌活性。该盐可以和药学可以接受的载体或赋形剂混合制备成抗真菌药物。该盐合成步骤短,设备技术条件和工艺流程简单,原材料来源充裕,适合扩大化生产。
Description
技术领域
本发明属于药物合成技术领域,具体涉及一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐及其制备方法和应用。
背景技术
侵袭性真菌感染是指病原真菌侵入人体各个器官及全身血液而引发的一种深部感染。常见的侵袭性真菌病原体是以念珠菌为主的酵母样真菌和以隐球菌为主的隐球真菌。此外,由于临床抗真菌药物使用频次的增加,单一耐药菌株及多重耐药菌株相继出现,真菌耐药性问题日益严重,这使得新型抗真菌药物的研发变得尤为重要。
20世纪60年代FDA批准顺铂用于睾丸癌的治疗后,相关铂系金属及其他过渡金属配合物在医学方面的研究与开发得到了极大的促进。其中钌(II)配合物由于具有较强的DNA结合能力,较好的药理特性且配体交换动力学类似于铂配合物,故被认为是铂类药物潜在的替代品。目前金属钌(II)配合物主要在抗癌、生物成像等方面有较深入的研究。经前人的研究表明,含有多吡啶配体的钌配合物对大多数革兰氏阳性菌表现出较好的抗菌活性,一些双核多吡啶钌(II)配合物也被证实具有很好的抗革兰氏阴性菌活性。在抗菌方面主要集中于细菌例如金黄色葡萄球菌、枯草芽孢杆菌及大肠杆菌等,但在抗真菌方面的研究尚处于起步阶段。但是将含有类似结构的吩嗪类钌(II)配合物六氟磷酸盐用于侵袭性真菌感染中新生隐球菌的灭杀还未见报道。
发明内容
针对上述现有技术,本发明提供一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐及其制备方法和应用,以提供一种新的隐球菌抑制方案。
为了达到上述目的,本发明所采用的技术方案是:提供一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐,吩嗪类钌(Ⅱ)配合物六氟磷酸盐的结构式如式(I)所示:
其中,分别独立的为/>
在上述技术方案的基础上,本发明还可以做如下改进。
进一步,式(I)所示的结构式中相同。
进一步,吩嗪类钌(Ⅱ)配合物六氟磷酸盐为具有如下结构式的化合物中的一种:
本发明还公开了用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐的制备方法,包括以下步骤:
S1:制备如式(II)所示的吩嗪类配体;
S2:制备如式(III)所示的钌(Ⅱ)前体配合物;
其中,分别独立的为/>
S3:将钌(Ⅱ)前体配合物和吩嗪类配体共溶于溶剂中,然后于120~150℃下反应3~5h,再经六氟磷酸铵盐和硅胶柱层析后,即得。
制备方法还可以做如下进一步的改进。
进一步,如式(II)所示的吩嗪类配体经过以下步骤制得:
将1,10-菲罗啉-5,6-二酮和4-氯-5-氟-1,2-苯二胺、4-氯-1,2-苯二胺、3-甲基-1,2-苯二胺或4,5-二甲基-1,2-苯二胺按1:1~1.5的摩尔比共溶于溶剂中,于90~110℃下加热回流4小时;然后去除溶剂,再于-15~-25℃下冷却结晶,随后洗涤、干燥,即得。
进一步,如式(III)所示的钌(Ⅱ)前体配合物经过以下步骤制得:
将含有的化合物与LiCl按1~5:1的摩尔比共溶于溶剂中,于保护气氛围下以170~200℃的温度回流7~9h,然后加入丙酮,并于-15~-25℃下冷冻过夜,再过滤、干燥,即得。
进一步,S3中溶剂为乙二醇与水按4:3的体积比混合后的混合溶剂。
本发明还公开了用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐在制备抑制隐球菌的药物中的应用。特别的,药物抑制的隐球菌为新生隐球菌H99或新生隐球菌5-FC。
本发明的有益效果是:本发明提供了吩嗪类配体和吩嗪类钌(Ⅱ)配合物六氟磷酸盐及其制备方法和应用,该盐以钌金属离子为核心,以1,10-菲啰啉或联吡啶及其衍生物为骨架配体,以DPPZ-F,Cl、DPPZ-Cl、DPPZ-Me和BPPX为配体,其性质稳定,对新生隐球菌具有良好的抗菌活性。该盐可以和药学可以接受的载体或赋形剂混合制备成抗真菌药物。该盐合成步骤短,设备技术条件和工艺流程简单,原材料来源充裕,适合扩大化生产。
具体实施方式
下面结合实施例对本发明的具体实施方式做详细的说明。
实施例1
一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐(cis-[Ru(phen)2(DPPZ-F,Cl)](PF6)2,Ru-1),其结构式如下:
该吩嗪类钌(Ⅱ)配合物六氟磷酸盐经过以下步骤制得:
1、制备吩嗪类配体(DPPZ-F,Cl)
称取1,10-菲罗啉-5,6-二酮213.8mg和4-氯-5-氟-1,2-苯二胺212.7mg加入100mL圆底烧瓶中,然后加入无水乙醇20mL;在100℃油浴条件下加热回流4小时。反应结束后,将溶液冷却至室温,溶液37℃旋蒸除去部分乙醇,将圆底烧瓶放入-20℃冰箱中冷却析晶;再将放置后的溶液过滤,用无水甲醇洗涤,液氮真空干燥1h,制得配体DPPZ-F,Cl,其反应方程式如下。
2、制备钌(Ⅱ)前体配合物(cis-[Ru(phen)2Cl2]·2H2O)
称取phen 5.406g,RuCl3·nH2O 3.9g,LiCl 0.427g混合于圆底烧瓶中,加入30mLN,N-二甲基甲酰胺,在N2保护下180℃回流8h,静置冷却;随后加入50mL丙酮,轻微振荡片刻后置于-20℃冰箱冷冻过夜,真空泵抽滤,冰水冲洗滤饼至滤液澄清无色,液氮下真空干燥2h,制得钌(Ⅱ)前体配合物。反应方程式如下。
3、制备cis-[Ru(phen)2(DPPZ-F,Cl)](PF6)2
称取cis-[Ru(phen)2Cl2]·2H2O 50.59mg与DPPZ-F,Cl 36.0mg混合于高温高压反应瓶中,加入乙二醇4mL和水3mL,加热至130℃反应4h;静置冷却,加入过量的六氟磷酸铵及25mL水充分振荡,离心去除上清液,重复两次;硅胶柱纯化,用乙腈饱和硅胶柱,梯度洗脱,洗脱剂终比例为乙腈:水:饱和KNO3=80:3:1的流动相进行梯度洗脱,减压旋蒸至圆底烧瓶中仅有1-2mL溶剂时,加入过量的水、少量的无水乙醇离心洗涤,倾去上清液,贴壁固体加入适量纯乙腈溶解,减压蒸发,真空干燥,即得,产率为58%。反应方程式如下。
cis-[Ru(phen)2(DPPZ-F,Cl)](PF6)2:1H NMR(400MHz,CD3CN)δ8.98(ddd,J=8.2,4.9,1.3Hz,2H),8.30(d,J=7.8Hz,1H),8.23(td,J=8.3,1.3Hz,4H),7.99(d,J=9.6Hz,1H),7.83(s,4H),7.70(dd,J=5.3,1.3Hz,2H),7.64(dt,J=5.4,1.6Hz,2H),7.48(dd,J=5.2,1.3Hz,2H),7.36(ddd,J=8.3,5.4,1.7Hz,2H),7.22(ddd,J=16.2,8.3,5.3Hz,4H).13CNMR(101MHz,CD3CN)δ158.97,155.62,155.51,154.25,153.95,152.09,151.95,148.86,148.80,141.10,137.99,137.94,134.54,134.38,132.08,132.06,131.92,131.92,131.39,131.26,129.36,129.09,129.07,128.33,128.31,126.94,126.90,114.91,114.69.
实施例2
一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐(cis-[Ru(TMphen)2(DPPZ-F,Cl)](PF6)2,Ru-2),其结构式如下:
该吩嗪类钌(Ⅱ)配合物六氟磷酸盐经过以下步骤制得:
1、制备吩嗪类配体(DPPZ-F,Cl)
制备方法同实施例1。
2、制备钌(Ⅱ)前体配合物(cis-[Ru(TMphen)2Cl2]·2H2O)
称取TMphen 7.110g,RuCl3·nH2O 3.9g,LiCl 0.427g混合于圆底烧瓶中,加入30mLN,N-二甲基甲酰胺,在N2保护下180℃回流8h,静置冷却;随后加入50mL丙酮,轻微振荡片刻后置于-20℃冰箱冷冻过夜,真空泵抽滤,冰水冲洗滤饼至滤液澄清无色,液氮下真空干燥2h,制得钌(Ⅱ)前体配合物。反应方程式如下。
3、制备cis-[Ru(TMphen)2(DPPZ-F,Cl)](PF6)2
称取cis-[Ru(TMphen)2Cl2]·2H2O 55.6mg与DPPZ-F,Cl 36.0mg混合于高温高压反应瓶中,加入乙二醇4mL和水3mL,加热至130℃反应4h。后处理同实施例1,制得[Ru(TMphen)2(DPPZ-F,Cl)](PF6)2;产率为47%。
cis-[Ru(TMphen)2(DPPZ-F,Cl)](PF6)2:1H NMR(400MHz,CD3CN)δ8.95–8.86(m,2H),8.21(d,J=7.7Hz,1H),8.06–7.88(m,5H),7.55(dt,J=5.4,1.3Hz,2H),7.39–7.29(m,4H),7.16(s,2H),2.21(s,12H),1.67(s,12H).13C NMR(101MHz,CD3CN)δ155.20,155.10,154.31,153.67,147.44,147.35,145.80,145.77,140.85,135.82,135.66,133.86,133.70,131.78,131.13,131.01,130.49,130.48,128.03,128.01,125.18,125.08,118.26,114.81,114.59,17.87,17.78,15.03,15.01.
实施例3
一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐(cis-[Ru(bpy)2(DPPZ-F,Cl)](PF6)2,Ru-3),其结构式如下:
该吩嗪类钌(Ⅱ)配合物六氟磷酸盐经过以下步骤制得:
1、制备吩嗪类配体(DPPZ-F,Cl)
制备方法同实施例1。
2、制备钌(Ⅱ)前体配合物(cis-[Ru(bpy)2Cl2]·2H2O)
称取bpy 4.71g,RuCl3·nH2O 3.9g,LiCl 0.427g混合于圆底烧瓶中,加入30mL N,N-二甲基甲酰胺,在N2保护下180℃回流8h,静置冷却;随后加入50mL丙酮,轻微振荡片刻后置于-20℃冰箱冷冻过夜,真空泵抽滤,冰水冲洗滤饼至滤液澄清无色,液氮下真空干燥2h,制得钌(Ⅱ)前体配合物。反应方程式如下。
3、制备cis-[Ru(bpy)2(DPPZ-F,Cl)](PF6)2
称取cis-[Ru(bpy)2Cl2]·2H2O 44.1mg与DPPZ-F,Cl 36.0mg混合于高温高压反应瓶中,加入乙二醇4mL和水3mL,加热至130℃反应4h。后处理同实施例1,制得[Ru(bpy)2(DPPZ-F,Cl)](PF6)2;产率为87%。
cis-[Ru(bpy)2(DPPZ-F,Cl)](PF6)2:1H NMR(400MHz,CD3CN)δ9.60(ddd,J=8.3,6.1,1.3Hz,2H),8.66(d,J=7.7Hz,1H),8.54(ddt,J=12.9,8.2,1.1Hz,4H),8.27(d,J=9.5Hz,1H),8.19(dt,J=5.4,1.4Hz,2H),8.12(td,J=8.0,1.5Hz,2H),8.02(td,J=7.9,1.5Hz,2H),7.95–7.82(m,4H),7.72(ddt,J=5.6,1.5,0.7Hz,2H),7.47(ddd,J=7.6,5.6,1.3Hz,2H),7.26(ddd,J=7.3,5.6,1.3Hz,2H).13C NMR(101MHz,CD3CN)δ161.54,158.99,158.18,157.98,155.09,154.98,153.12,152.96,151.71,151.56,143.40,141.81,141.10,139.01,138.93,134.62,134.46,131.93,131.92,131.50,131.38,129.17,128.63,128.55,128.53,128.48,125.34,125.28,114.91,114.69.
实施例4
一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐(cis-[Ru(4,4'-dmbpy)2(DPPZ-F,Cl)](PF6)2,Ru-4),其结构式如下:
该吩嗪类钌(Ⅱ)配合物六氟磷酸盐经过以下步骤制得:
1、制备吩嗪类配体(DPPZ-F,Cl)
制备方法同实施例1。
2、制备钌(Ⅱ)前体配合物(cis-[Ru(4,4'-dmbpy)2Cl2]·2H2O)
称取4,4'-dmbpy 5.526g,RuCl3·nH2O 3.9g,LiCl 0.427g混合于圆底烧瓶中,加入30mLN,N-二甲基甲酰胺,在N2保护下180℃回流8h,静置冷却;随后加入50mL丙酮,轻微振荡片刻后置于-20℃冰箱冷冻过夜,真空泵抽滤,冰水冲洗滤饼至滤液澄清无色,液氮下真空干燥2h,制得钌(Ⅱ)前体配合物。反应方程式如下。
3、制备cis-[Ru(4,4'-dmbpy)2(DPPZ-F,Cl)](PF6)2
称取cis-[Ru(4,4'-dmbpy)2Cl2]·2H2O 44.1mg与DPPZ-F,Cl 36.0mg混合于高温高压反应瓶中,加入乙二醇4mL和水3mL,加热至130℃反应4h。后处理同实施例1,制得[Ru(4,4'-dmbpy)2(DPPZ-F,Cl)](PF6)2;产率为29%。
cis-[Ru(4,4'-dmbpy)2(DPPZ-F,Cl)](PF6)2:1H NMR(400MHz,CD3CN)δ9.57(ddd,J=8.2,6.1,1.3Hz,2H),8.66(d,J=7.8Hz,1H),8.41–8.38(m,2H),8.37–8.35(m,2H),8.27(d,J=9.5Hz,1H),8.19(dt,J=5.4,1.5Hz,2H),7.88(dd,J=8.2,5.4Hz,2H),7.64(d,J=5.8Hz,2H),7.51(d,J=5.8Hz,2H),7.33–7.26(m,2H),7.11–7.05(m,2H),2.58(s,6H),2.48(s,6H).13C NMR(101MHz,CD3CN)δ157.73,157.55,154.94,154.83,152.25,151.93,151.86,151.79,151.50,151.41,141.88,141.09,134.20,134.04,131.92,131.40,131.28,129.27,129.09,128.42,128.41,125.93,125.90,114.91,114.69,21.29,21.21.
实施例5
一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐(cis-[Ru(5,5'-dmbpy)2(DPPZ-F,Cl)](PF6)2,Ru-5),其结构式如下:
该吩嗪类钌(Ⅱ)配合物六氟磷酸盐经过以下步骤制得:
1、制备吩嗪类配体(DPPZ-F,Cl)
制备方法同实施例1。
2、制备钌(Ⅱ)前体配合物(cis-[Ru(5,5'-dmbpy)2Cl2]·2H2O)
称取5,5'-dmbpy 5.527g,RuCl3·nH2O 3.9g,LiCl 0.427g混合于圆底烧瓶中,加入30mLN,N-二甲基甲酰胺,在N2保护下180℃回流8h,静置冷却;随后加入50mL丙酮,轻微振荡片刻后置于-20℃冰箱冷冻过夜,真空泵抽滤,冰水冲洗滤饼至滤液澄清无色,液氮下真空干燥2h,制得钌(Ⅱ)前体配合物。反应方程式如下。
3、制备cis-[Ru(5,5'-dmbpy)2(DPPZ-F,Cl)](PF6)2
称取cis-[Ru(5,5'-dmbpy)2Cl2]·2H2O 44.1mg与DPPZ-F,Cl 36.0mg混合于高温高压反应瓶中,加入乙二醇4mL和水3mL,加热至130℃反应4h。后处理同实施例1,制得[Ru(5,5'-dmbpy)2(DPPZ-F,Cl)](PF6)2;产率为73%。
cis-[Ru(5,5'-dmbpy)2(DPPZ-F,Cl)](PF6)2:1H NMR(400MHz,CD3CN)δ9.64–9.56(m,2H),8.65(d,J=7.7Hz,1H),8.35(dd,J=16.3,8.4Hz,4H),8.27(d,J=9.4Hz,1H),8.20–8.12(m,2H),7.95–7.85(m,4H),7.83–7.77(m,2H),7.62–7.56(m,2H),7.42(s,2H),2.25(s,6H),2.04(s,6H).13C NMR(101MHz,CD3CN)δ158.98,155.73,155.47,155.05,154.95,152.75,152.67,151.91,151.76,143.32,143.19,141.99,141.47,141.01,139.40,139.37,139.21,139.19,134.35,134.19,131.90,131.89,131.42,131.30,129.13,128.39,128.36,124.29,124.22,114.90,114.69,18.61,18.45.
实施例6
一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐(cis-[Ru(4,4'-dmbpy)2(DPPZ-Cl)](PF6)2,Ru-6),其结构式如下:
该吩嗪类钌(Ⅱ)配合物六氟磷酸盐经过以下步骤制得:
1、制备吩嗪类配体(DPPZ-Cl)
称取1,10-菲罗啉-5,6-二酮213.8mg和4-氯-1,2-苯二胺185.2mg加入100mL圆底烧瓶中,然后加入无水乙醇20mL;在100℃油浴条件下加热回流4小时。后处理同实施例1,制得配体DPPZ-Cl,其反应方程式如下。
2、制备钌(Ⅱ)前体配合物(cis-[Ru(4,4'-dmbpy)2Cl2]·2H2O)
制备方法同实施例4。
3、制备cis-[Ru(4,4'-dmbpy)2(DPPZ-Cl)](PF6)2
称取cis-[Ru(4,4'-dmbpy)2Cl2]·2H2O 44.1mg与DPPZ-Cl 34.2mg混合于高温高压反应瓶中,加入乙二醇4mL和水3mL,加热至130℃反应4h。后处理同实施例1,制得[Ru(4,4'-dmbpy)2(DPPZ-Cl)](PF6)2;产率为45.7%。
cis-[Ru(4,4'-dmbpy)2(DPPZ-Cl)](PF6)2:1H NMR(400MHz,CD3CN)δ9.62(ddd,J=8.3,4.5,1.3Hz,2H),8.54(d,J=2.3Hz,1H),8.48(d,J=9.2Hz,1H),8.41(d,J=14.4Hz,4H),8.21(td,J=3.7,1.7Hz,2H),8.12(dd,J=9.1,2.4Hz,1H),7.90(ddd,J=7.6,5.4,1.9Hz,2H),7.67(d,J=5.8Hz,2H),7.54(d,J=5.8Hz,2H),7.33(dd,J=6.1,1.7Hz,2H),7.11(d,J=5.8Hz,2H),2.60(s,6H),2.51(s,6H).13C NMR(101MHz,CD3CN)δ157.37,157.18,154.46,154.33,151.86,151.57,151.48,151.39,151.03,143.48,142.00,141.46,140.94,138.48,133.87,133.81,133.73,131.87,128.89,128.82,128.72,128.00,125.52,20.92.
实施例7
一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐(cis-[Ru(4,4'-dmbpy)2(DPPZ-CH3)](PF6)2,Ru-7),其结构式如下:
该吩嗪类钌(Ⅱ)配合物六氟磷酸盐经过以下步骤制得:
1、制备吩嗪类配体(DPPZ-CH3)
称取1,10-菲罗啉-5,6-二酮213.8mg和3-甲基-1,2-苯二胺159.9mg加入100mL圆底烧瓶中,然后加入无水乙醇20mL;在100℃油浴条件下加热回流4小时。后处理同实施例1,制得配体DPPZ-CH3,其反应方程式如下。
2、制备钌(Ⅱ)前体配合物(cis-[Ru(4,4'-dmbpy)2Cl2]·2H2O)
制备方法同实施例4。
3、制备cis-[Ru(4,4'-dmbpy)2(DPPZ-CH3)](PF6)2
称取cis-[Ru(4,4'-dmbpy)2Cl2]·2H2O 44.1mg与DPPZ-CH332.0mg混合于高温高压反应瓶中,加入乙二醇4mL和水3mL,加热至130℃反应4h。后处理同实施例1,制得[Ru(4,4'-dmbpy)2(DPPZ-CH3)](PF6)2;产率为51.1%。
cis-[Ru(4,4'-dmbpy)2(DPPZ-F,Cl)](PF6)2:1H NMR(400MHz,CD3CN)δ9.92(s,1H),9.66(d,J=8.2Hz,2H),9.08(d,J=5.9Hz,1H),8.45–8.39(m,4H),8.32(d,J=5.9Hz,1H),8.24(ddd,J=6.9,5.3,1.3Hz,2H),7.93(ddd,J=7.8,5.4,2.0Hz,2H),7.67(d,J=5.8Hz,2H),7.56(d,J=5.8Hz,2H),7.33(dd,J=5.8,1.8Hz,2H),7.12(d,J=5.4Hz,2H),2.61(s,6H),2.51(s,6H).13C NMR(101MHz,CD3CN)δ157.74,157.54,154.39,152.21,152.17,151.83,151.64,151.42,151.32,143.96,142.91,139.78,139.34,134.16,133.98,133.37,132.75,131.94,131.72,129.22,129.06,128.32,128.19,125.88,125.85,21.26,21.17,17.31.
实施例8
一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐(cis-[Ru(4,4'-dmbpy)2(BPPX)](PF6)2,Ru-8),其结构式如下:
该吩嗪类钌(Ⅱ)配合物六氟磷酸盐经过以下步骤制得:
1、制备吩嗪类配体(BPPX)
称取1,10-菲罗啉-5,6-二酮213.8mg和4,5-二甲基-1,2-苯二胺178.1mg加入100mL圆底烧瓶中,然后加入无水乙醇20mL;在100℃油浴条件下加热回流4小时。后处理同实施例1,制得配体BPPX,其反应方程式如下。
2、制备钌(Ⅱ)前体配合物(cis-[Ru(4,4'-dmbpy)2Cl2]·2H2O)
制备方法同实施例4。
3、制备cis-[Ru(4,4'-dmbpy)2(BPPX)](PF6)2
称取cis-[Ru(4,4'-dmbpy)2Cl2]·2H2O 44.1mg与BPPX33.5mg混合于高温高压反应瓶中,加入乙二醇4mL和水3mL,加热至130℃反应4h。后处理同实施例1,制得[Ru(4,4'-dmbpy)2(BPPX)](PF6)2;产率为53.2%。
cis-[Ru(4,4'-dmbpy)2(BPPX)](PF6)2:1H NMR(400MHz,CD3CN)δ9.63(dd,J=8.3,1.3Hz,2H),8.37(dd,J=16.8,8.4Hz,4H),8.26–8.19(m,2H),8.14(dd,J=5.4,1.3Hz,2H),7.94(ddd,J=8.4,1.9,0.8Hz,2H),7.89(dd,J=8.2,5.4Hz,2H),7.82(ddd,J=8.4,1.9,0.9Hz,2H),7.64–7.61(m,2H),7.47–7.44(m,2H),2.72–2.65(m,6H),2.27(s,6H),2.06(s,6H).13C NMR(101MHz,CD3CN)δ155.38,155.15,153.90,152.37,152.32,150.84,144.98,142.45,139.79,138.98,138.84,138.80,133.58,131.40,128.53,127.67,123.91,123.84,20.45,18.24,18.09.
实验例
采用符合美国临床实验标准协会(Clinical and Laboratory StandarsInstitut,CLSI)中的肉汤稀释法检测所合成的吩嗪类钌(Ⅱ)配合物六氟磷酸盐对新生隐球菌H99和新生隐球菌5-FC的最低抑菌浓度(MIC)和最低杀菌浓度(MFC),将待测盐用DMSO溶解并稀释制成浓度为1280μg/mL的溶液,再用培养液稀释至不同浓度,35℃培养48h,在波长600nm处测定吸光度,通过计算抑制率达到50%时的最低浓度即为MIC50值,通过观察平板中菌落量的情况,未长菌的配合物浓度即为MFC值。测得配合物对新生隐球菌H99和新生隐球菌5-FC的MIC50和MFC数值,结果见表1和表2。
表1 Ru-1~Ru-8对体外抗新生隐球菌H99活性数据
表2 Ru-1~Ru-8对体外抗新生隐球菌5-FC活性数据
由表1和表2可知,本发明中Ru-1~Ru-8的MIC50和MFC值都大不于阳性对照药物氟康唑,说明卤代吩嗪类钌(Ⅱ)配合物六氟磷酸盐对新生隐球菌H99和新生隐球菌5-FC具有良好的抗菌活性。
虽然结合实施例对本发明的具体实施方式进行了详细地描述,但不应理解为对本专利的保护范围的限定。在权利要求书所描述的范围内,本领域技术人员不经创造性劳动即可作出的各种修改和变形仍属本专利的保护范围。
Claims (2)
1.一种用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐,其特征在于,所述吩嗪类钌(Ⅱ)配合物六氟磷酸盐为具有如下结构式的化合物中的一种:
、/>
、/>
、/>
或/>。
2.如权利要求1所述的用于抑制隐球菌的吩嗪类钌(Ⅱ)配合物六氟磷酸盐在制备抗新生隐球菌H99或新生隐球菌5-FC的药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211191586.5A CN115583978B (zh) | 2022-09-28 | 2022-09-28 | 一种用于抑制隐球菌的吩嗪类钌(ⅱ)配合物六氟磷酸盐及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211191586.5A CN115583978B (zh) | 2022-09-28 | 2022-09-28 | 一种用于抑制隐球菌的吩嗪类钌(ⅱ)配合物六氟磷酸盐及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115583978A CN115583978A (zh) | 2023-01-10 |
CN115583978B true CN115583978B (zh) | 2024-04-16 |
Family
ID=84778189
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211191586.5A Active CN115583978B (zh) | 2022-09-28 | 2022-09-28 | 一种用于抑制隐球菌的吩嗪类钌(ⅱ)配合物六氟磷酸盐及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115583978B (zh) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114149469A (zh) * | 2021-12-06 | 2022-03-08 | 有头猪农牧科技(重庆)有限公司 | 钌配合物、狂犬病毒衍生肽和脂质体修饰的钌配合物 |
-
2022
- 2022-09-28 CN CN202211191586.5A patent/CN115583978B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114149469A (zh) * | 2021-12-06 | 2022-03-08 | 有头猪农牧科技(重庆)有限公司 | 钌配合物、狂犬病毒衍生肽和脂质体修饰的钌配合物 |
Non-Patent Citations (7)
Title |
---|
Combining a Ru(II) "Building Block" and Rapid Screening Approach to Identify DNA Structure-Selective "Light Switch" Compounds;Erin Wachter et al.;《ACS Comb. Sci. 》;20161128;第19卷;92页,图1 * |
Discovery of polypyridyl iridium(III) complexes as potent agents against resistant Candida albicans;Chen Fu et al.;《European Journal of Medicinal Chemistry》;20220303;第233卷;114250(1-11) * |
Jtirg Fees et al..Electronic Structure of the "Molecular Light Switch" [Ru(bpy)2(dppz)2+ (dppz = Dipyrido[3,2-a:2‘,3‘-c]phenazine). Cyclic Voltammetric,UV/Vis, and EPR/ENDOR Study of Multiply Reduced Complexes and Ligands .《Inorg. Chem.》.1993,第32卷167页. * |
Novel Dipyridophenazine Complexes of Ruthenium( II) :Exploring Luminescent Reporters of DNA;Richard M. Hartshorn et al.;《J. Am. Chem. SOC》;19920701;第114卷(第15期);表II、图2 * |
Role of Electronic Structure on DNA Light-Switch Behavior of Ru(II) Intercalators;Yujie Sun et al.;《Inorg. Chem. 》;20080621;第47卷;图1,6428页右栏第2段,6429页左栏第2段 * |
Synthesis, characterization and DNA binding and photocleavage studies of [Ru(bpy)2BDPPZ]2+, [Ru(dmb)2BDPPZ]2+ and [Ru(phen)2BDPPZ]2+ complexes and their antimicrobial activity;K. Ashwini Kumar et al.;《Appl. Organometal. Chem.》;20090824;第23卷;409–420 * |
Venugopal Rajendiran et al..New [Ru(5,6-dmp/3,4,7,8-tmp)2(diimine)]2+ complexes: Non-covalent DNA and protein binding, anticancer activity and fluorescent probes for nuclear and protein components.《Journal of Inorganic Biochemistry》.2012,第116卷159页、Scheme 1、160页4.4.5节、4.3-4.4节. * |
Also Published As
Publication number | Publication date |
---|---|
CN115583978A (zh) | 2023-01-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Smoleński et al. | New water-soluble polypyridine silver (I) derivatives of 1, 3, 5-triaza-7-phosphaadamantane (PTA) with significant antimicrobial and antiproliferative activities | |
Günal et al. | Novel benzimidazolium salts and their silver complexes: Synthesis and antibacterial properties | |
Varbanov et al. | Novel tetracarboxylatoplatinum (IV) complexes as carboplatin prodrugs | |
DK174981B1 (da) | 1,2-Bis(aminomethyl)cyclobutan-platin-komplekser, fremgangsmåde til fremstilling heraf, lægemiddel indeholdende samme og fremgangsmåde til fremstilling af et lægemiddel samt anvendelse af komplekserne | |
Kamatchi et al. | New organometallic ruthenium (II) complexes containing chelidonic acid (4-oxo-4 H-pyran-2, 6-dicarboxylic acid): synthesis, structure and in vitro biological activity | |
US20210246154A1 (en) | Ruthenium complex containing alkynyl group, method of synthesizing the same and use thereof | |
CN107698697B (zh) | 一种爪型1,4-三氮唑多连环糊精分子及其制备方法与应用 | |
CN110305166B (zh) | 一种以姜黄素衍生物为配体的钌(ii)配合物及其制备方法和应用 | |
CN110078695B (zh) | 一种槲皮素衍生物及其制备方法 | |
CN115583978B (zh) | 一种用于抑制隐球菌的吩嗪类钌(ⅱ)配合物六氟磷酸盐及其制备方法和应用 | |
CN107417580A (zh) | 一类具有抗肿瘤活性的棉酚‑l‑精氨酸席夫碱类化合物及其合成方法 | |
CN107286220B (zh) | 1,2,4-三氮唑偶联的二氢杨梅素衍生物及其制备方法和应用 | |
CN106478734B (zh) | 一种具有抗癌活性的吡唑官能团化的氮杂环卡宾钌化合物及其制备方法和应用 | |
CN107043354B (zh) | 一种具有抗真菌活性的2-苯并咪唑基苯甲酸铜配合物及制备方法 | |
CN103254191B (zh) | 取代芳香四环类抗真菌化合物及其制备方法与应用 | |
CN113441184B (zh) | 碳二亚胺胺化合成用催化剂、合成方法及所得胍基化合物 | |
EP2243773B1 (en) | Platinum complex compound and utilization of the same | |
CN113620883B (zh) | 一种半质子型化合物的制备方法及其产品和应用 | |
Beato et al. | Synthesis and biological evaluation of fluoro-substituted cationic and neutral antibiotic NHC* silver derivatives of SBC3 | |
CN112480172A (zh) | 硼烷-吡啶络合物在制备药物化合物中的用途 | |
Kaushal et al. | In vitro anticancer and antibacterial activities of octahedral ruthenium (III) complexes with hydroxamic acids. Synthesis and spectroscopic characterization | |
CN110903338B (zh) | 具有抗肿瘤活性的含硫脲砷糖及其制备方法和应用 | |
CN111646966A (zh) | 一种香豆素修饰的荧光型环铱(iii)配合物及其制备方法和应用 | |
CN104093718A (zh) | 用于2-苯基-[1,2,4]三唑并[1,5-a]吡啶衍生物的制备的方法 | |
CN110396106B (zh) | 一种咪唑[1,5-a]吡啶鎓盐及其制备方法和应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |