CN110251513A - 一种含吡唑的中氮茚化合物在制备抗肿瘤药物中的应用 - Google Patents
一种含吡唑的中氮茚化合物在制备抗肿瘤药物中的应用 Download PDFInfo
- Publication number
- CN110251513A CN110251513A CN201910595444.7A CN201910595444A CN110251513A CN 110251513 A CN110251513 A CN 110251513A CN 201910595444 A CN201910595444 A CN 201910595444A CN 110251513 A CN110251513 A CN 110251513A
- Authority
- CN
- China
- Prior art keywords
- cancer
- tumor
- tumour
- indolizine compounds
- cyano
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- 125000003406 indolizinyl group Chemical class C=1(C=CN2C=CC=CC12)* 0.000 title claims abstract 3
- 239000002246 antineoplastic agent Substances 0.000 title abstract description 5
- 229940041181 antineoplastic drug Drugs 0.000 title abstract description 5
- 150000003217 pyrazoles Chemical class 0.000 title description 5
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 47
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 6
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 5
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims abstract description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 5
- 201000005202 lung cancer Diseases 0.000 claims abstract description 5
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 5
- 206010005003 Bladder cancer Diseases 0.000 claims abstract description 4
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims abstract description 4
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 claims abstract description 4
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims abstract description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims abstract description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims abstract description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 4
- 210000003734 kidney Anatomy 0.000 claims abstract description 4
- 201000007270 liver cancer Diseases 0.000 claims abstract description 4
- 208000014018 liver neoplasm Diseases 0.000 claims abstract description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims abstract description 4
- 201000001441 melanoma Diseases 0.000 claims abstract description 4
- 201000011216 nasopharynx carcinoma Diseases 0.000 claims abstract description 4
- 201000008968 osteosarcoma Diseases 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims abstract description 4
- 206010062129 Tongue neoplasm Diseases 0.000 claims abstract description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims abstract description 3
- 208000023958 prostate neoplasm Diseases 0.000 claims abstract description 3
- 201000006134 tongue cancer Diseases 0.000 claims abstract description 3
- 206010046766 uterine cancer Diseases 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 3
- 230000000259 anti-tumor effect Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 19
- 201000011510 cancer Diseases 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- 150000002478 indolizines Chemical class 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 238000011729 BALB/c nude mouse Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 1
- 240000002853 Nelumbo nucifera Species 0.000 description 1
- 235000006508 Nelumbo nucifera Nutrition 0.000 description 1
- 235000006510 Nelumbo pentapetala Nutrition 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 208000033147 Parenteral nutrition-associated cholestasis Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- KDPAWGWELVVRCH-UHFFFAOYSA-M bromoacetate Chemical compound [O-]C(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-M 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 210000004043 pneumocyte Anatomy 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明属于生物化学制药技术领域，具体涉及一种化学名称为5‑甲基‑1‑氰基‑3‑(3，5‑二甲基吡唑基羰基)中氮茚化合物在制备抗肿瘤药物中的应用。中氮茚化合物在体内实验中表现出良好的抗肿瘤活性，可制备成治疗肿瘤的药物，所述肿瘤为舌癌或骨肉瘤或食管癌或乳腺癌或结肠癌或肺癌或肝癌或前列腺瘤或肾癌或卵巢癌或子宫癌或胰腺癌或膀胱癌或黑色素瘤或喉癌或鼻咽癌。
Description
技术领域
本发明属于生物化学制药技术领域，具体涉及一种化学名称为5-甲基-1-氰基-3-(3，5-二甲基吡唑基羰基)中氮茚化合物在制备抗肿瘤药物中的应用。
背景技术
中国癌症发病率和死亡率持续上升，已经成为最主要的疾病死亡原因。2019年1月，国家癌症中心发布最新一期的全国癌症统计数据，报告显示，2015年全国恶性肿瘤发病约392.9万人，较2014年的380.4万增加了12.5万，增长率为3.2％，这意味着，平均每天超过1万人被确诊为癌症，每分钟有7.5人被确诊为癌症。其中男性发病前五位是肺癌、胃癌、肝癌、结肠癌和食道癌，女性发病前五位是乳腺癌、肺癌、结直肠癌、甲状腺癌和胃癌。目前，针对肿瘤的放化疗及免疫治疗取得了一定的进展，但因其毒副作用较大，价格昂贵，对实体瘤效果较差，限制了部分药物的使用。因此，现有的抗肿瘤药物，无法满足日益增长的癌症患者的需要，新型抗肿瘤药物的研发和设计，仍是研究的重要方向。
发明内容
本发明需要解决的技术问题是提供一种用于治疗癌症的化合物，本发明所述用于治疗癌症的化合物是一种含吡唑的中氮茚衍生物5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)，其结构为：
本发明通过体内对肿瘤模型进行例证。此处的动物包括但是不限于：小鼠，大鼠，驯养动物包括但是不限于猫，狗，以及其它一些动物，例如但是不限于牛，羊，猪，马，灵长类动物，例如但是不限于猴子和人。小鼠肿瘤模型的体内检测是被广泛认可和接受的体内药物活性检测的模型，同时也可以为其它生物，例如但是不限于人提供参考。
本发明是通过体内生物活性测定实验实现的，但是不应被视作对此化合物的功能范围的限定。
本发明涉及一种含吡唑的中氮茚衍生物5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚的药用组合物，该药物组合物包含治疗有效量的游离形式或药用盐形式的符合通式的化合物作为活性成分，一种或多种药用载体物质和/或稀释剂。
本发明涉及一种含吡唑的中氮茚衍生物5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚的药用组合物，包括制备成胶囊，片剂，口服液和注射液等。
本发明涉及所述化合物对人肿瘤异体移位瘤治疗的应用：
(1)多种人肿瘤细胞分别接种于SPF级BALB/c裸鼠右前肢腋部皮下(1x106个细胞/鼠)，建立肿瘤模型，并观察记录荷瘤小鼠生长情况。
(2)当肿瘤直径(直径＝(长径+短径)/2)达到0.5cm时，将50mg/kg的5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚化合物采用腹腔注射对不同肿瘤模型进行治疗，每两日一次，小鼠连续给药14天。
(3)治疗14天后，末次给药24h后，脱颈椎处死，剥离肿瘤，根据瘤重的变化来计算5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚化合物对肿瘤抑制率，评价肿瘤的治疗效果。肿瘤抑制率的公式为：
本发明的有益效果：本发明针对恶性肿瘤发病率的不断上升，研究开发出一种治疗肿瘤的新药，进一步拓宽了候选化疗药物的种类。与现有化疗药物相比，5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚化合物合成方法简单，体内实验检测该化合物对多种肿瘤均有抑制效果，而且毒副作用较低。
具体实施方式
实施例1：5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚化合物的合成
(1)化合物合成方案参考专利CN106632322公开的合成方法，具体合成方法如下：120mmol 2-二甲基吡啶1和60mmol溴乙酸乙酯溶于200mL乙酸乙酯中，搅拌20小时。抽滤。将滤纸上固体用50mL乙酸乙酯洗涤后，室温干燥。产品2为白色粉末，收率为79％。
(2)30mmol产品2，180mmol三乙胺，120mmol丙烯腈和120mmol三氧化铬在180mL N,N-二甲基甲酰胺中加热到90℃，保持2小时。冷却后，反应混合物倒入500mL5％盐酸中，静置，抽滤，滤纸上固体晾干后，用石油醚(bp 60-90℃)-乙酸乙酯(体积比4:1)柱层析，产品3为黄色粉末，收率为44％。
(3)20mmol产品3与10mL乙醇，30mL 80％水合肼混合后，回流8小时。冷却，抽滤，产品4为白色粉末，收率为80％。
(4)10mmol产品4溶于20mL乙酸，随后将40mmol乙酰丙酮滴加入。搅拌2小时后，抽滤，滤纸上固体晾干后，用石油醚(bp 60-90℃)-乙酸乙酯(体积比4:1)柱层析，终产物5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚为白色粉末，熔点184-185，收率为70％。通过核磁图谱，确认5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚合成成功。
实施例2：5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚化合物抗人源肿瘤异体异位瘤活性研究
(1)细胞类型：人舌癌细胞株TCA8113、人骨肉瘤MNNG/HOS细胞、人食管癌细胞株FC-109、人乳腺癌MCF-7细胞、人结肠癌Lovo细胞、人肺癌A549细胞、人肝癌HepG2细胞、人前列腺癌PC-3细胞、人肾癌786-0细胞、人卵巢癌A2780细胞、人子宫内膜癌细胞株HEC-1B、人胰腺癌细胞株PNAC-1，来源于中国科学院上海生科院细胞资源中心；人膀胱癌细胞株BIU-87，购于同济医院妇科肿瘤实验室；人黑色素瘤细胞株MV3，购于南京凯基生物科技有限公司；人喉癌细胞株Hep-2，购于上海歌凡生物科技有限公司；人鼻咽癌细胞株CNE-2，购于中国医学科学院肿瘤研究所。
(2)小鼠类型：6-8周SPF级BALB/c裸鼠，购买于北京维通利华实验动物技术有限公司。
(3)各肿瘤细胞通过红细胞计数板计数活细胞，然后把各细胞调整为1×107/ml，接种于小鼠右前肢腋部皮下(0.1ml/鼠)，每天观察荷瘤小鼠生长情况，当肿瘤直径(直径＝(长径+短径)/2)达到0.5cm时，荷瘤小鼠被随机分两组：荷瘤对照组，5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)治疗组(50mg/kg)，每组10只。各给药组均采用瘤内注射给药，每两日一次，对照组给予同体积橄榄油。小鼠连续给药14天，末次给药24h后，脱颈椎处死，剥离肿瘤，根据瘤重的变化来计算5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)的肿瘤抑制率，评价肿瘤的治疗效果。5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)化合物对各种肿瘤的抑制率如表1。由这些结果可知：在人源肿瘤异体异位瘤模型中，化合物仍具有良好的抗肿瘤活性，能应用于肿瘤及其他与肿瘤相关的疾病的预防和/或治疗。可制备成治疗肿瘤的药物。所述肿瘤为舌癌或骨肉瘤或食管癌或乳腺癌或结肠癌或肺癌或肝癌或前列腺瘤或肾癌或卵巢癌或子宫癌或胰腺癌或膀胱癌或黑色素瘤或喉癌或鼻咽癌。
表1 5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)化合物抗人源肿瘤异体异位瘤活性：
Claims (2)
1.一种化学名称为5-甲基-1-氰基-3-(3,5-二甲基吡唑基羰基)中氮茚化合物在制备治疗肿瘤药物中的应用。
2.权利要求1所述的中氮茚化合物在制备治疗肿瘤药物中的应用，其特征是所述肿瘤为舌癌或骨肉瘤或食管癌或乳腺癌或结肠癌或肺癌或肝癌或前列腺瘤或肾癌或卵巢癌或子宫癌或胰腺癌或膀胱癌或黑色素瘤或喉癌或鼻咽癌。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910595444.7A CN110251513A (zh) | 2019-07-03 | 2019-07-03 | 一种含吡唑的中氮茚化合物在制备抗肿瘤药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910595444.7A CN110251513A (zh) | 2019-07-03 | 2019-07-03 | 一种含吡唑的中氮茚化合物在制备抗肿瘤药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110251513A true CN110251513A (zh) | 2019-09-20 |
Family
ID=67924098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910595444.7A Pending CN110251513A (zh) | 2019-07-03 | 2019-07-03 | 一种含吡唑的中氮茚化合物在制备抗肿瘤药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110251513A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114276343A (zh) * | 2020-09-27 | 2022-04-05 | 中石化南京化工研究院有限公司 | 用于检测氯化苯中微量铁离子的荧光探针的制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1649867A (zh) * | 2002-04-04 | 2005-08-03 | 赛诺菲安万特 | 新颖的1,2,3－取代的中氮茚衍生物,fgf抑制剂,制备它们的方法和含有它们的药物组合物 |
| US20060199962A1 (en) * | 2003-09-18 | 2006-09-07 | Sanofi-Aventis | Substituted indolizine 1,2,3,6,7,8 derivatives, FGFs inhibitors, a method for the preparation thereof and pharmaceutical compositions containing said derivatives |
| CN106632322A (zh) * | 2016-12-20 | 2017-05-10 | 南京师范大学 | 一类吡唑中氮茚化合物及其制备方法与用途 |
-
2019
- 2019-07-03 CN CN201910595444.7A patent/CN110251513A/zh active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1649867A (zh) * | 2002-04-04 | 2005-08-03 | 赛诺菲安万特 | 新颖的1,2,3－取代的中氮茚衍生物,fgf抑制剂,制备它们的方法和含有它们的药物组合物 |
| US20060199962A1 (en) * | 2003-09-18 | 2006-09-07 | Sanofi-Aventis | Substituted indolizine 1,2,3,6,7,8 derivatives, FGFs inhibitors, a method for the preparation thereof and pharmaceutical compositions containing said derivatives |
| CN106632322A (zh) * | 2016-12-20 | 2017-05-10 | 南京师范大学 | 一类吡唑中氮茚化合物及其制备方法与用途 |
Non-Patent Citations (1)
| Title |
|---|
| YONG FU等: "A novel pyrazole-containing indolizine derivative suppresses NF-κB activation and protects against TNBS-induced colitis via a PPAR-γ-dependent pathway", 《BIOCHEMICAL PHARMACOLOGY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114276343A (zh) * | 2020-09-27 | 2022-04-05 | 中石化南京化工研究院有限公司 | 用于检测氯化苯中微量铁离子的荧光探针的制备方法 |
| CN114276343B (zh) * | 2020-09-27 | 2023-07-07 | 中国石油化工股份有限公司 | 用于检测氯化苯中微量铁离子的荧光探针的制备方法 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104109193B (zh) | 一种抗癌活性肽变体及其应用 | |
| CN108619511A (zh) | 一种基于阿糖胞苷小分子前药的金属有机框架载药系统的制备方法和应用 | |
| CN108495628A (zh) | 苯并噻吩基选择性雌激素受体下调剂 | |
| CN109718208B (zh) | 多糖修饰的纳米硒复合物在恶性腹水治疗药物中的应用 | |
| CN108289895A (zh) | 噻吩并嘧啶衍生物及其用途 | |
| CN111544588B (zh) | 一类免疫活性肽-胆绿素的缀合物、其制备方法及应用 | |
| CN110251513A (zh) | 一种含吡唑的中氮茚化合物在制备抗肿瘤药物中的应用 | |
| CN105456200A (zh) | 一种提高难溶性药物口服生物利用度的纳米粒微球的制备方法及应用 | |
| WO2020057632A1 (zh) | 硒氰化合物及其用途 | |
| CN105267214B (zh) | N-杂芳基苯胺类化合物作为制备抗肿瘤药物的应用 | |
| CN110354097A (zh) | 一种五氟尿嘧啶纳米药物制剂的制备方法及其应用 | |
| CN112661812B (zh) | 一种kk-lc-1抗原靶向结合肽及其衍生物、探针与应用 | |
| CN100526324C (zh) | 制备反式-或顺式-二铵二氯二羟合铂(ⅳ)的方法及其用于制备药物有效物质的用途 | |
| CN104744518B (zh) | 金属钌配合物及其制备方法和应用 | |
| CN108853114B (zh) | 硝呋莫司在制备治疗癌症衍生的脑转移瘤的药物中的应用 | |
| CN103110623B (zh) | 色氨酸纳米微球在制备治疗肿瘤疾病药物中的用途 | |
| US20200038340A1 (en) | Pharmaceutical compound for treating colorectal cancer | |
| CN101830819B (zh) | 苯丁酰基姜黄素衍生物及其在制备抗肿瘤药物中的应用 | |
| CN109966275A (zh) | 醌式查尔酮化合物在制备抗肿瘤药物中的应用 | |
| CN105541696B (zh) | 一种抗肿瘤的化合物及其制备方法和应用 | |
| CN113801110B (zh) | 1,2,4-噁二唑杂环化合物及其应用 | |
| CN111170962A (zh) | 4-(苯并硒唑-2-基)芳胺类化合物治疗肠癌的用途 | |
| CN109369727A (zh) | 一种抗癌靶向配合物及其制备方法和应用 | |
| CN103965202B (zh) | 二环稠合杂环化合物、其制备方法及用途 | |
| CN112794852B (zh) | 一种含硒有机化合物及其制备方法与应用 |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190920 |
|
| WD01 | Invention patent application deemed withdrawn after publication |