CN106083960A - 新型紫杉类化合物及其制备方法和应用 - Google Patents
新型紫杉类化合物及其制备方法和应用 Download PDFInfo
- Publication number
- CN106083960A CN106083960A CN201610426133.4A CN201610426133A CN106083960A CN 106083960 A CN106083960 A CN 106083960A CN 201610426133 A CN201610426133 A CN 201610426133A CN 106083960 A CN106083960 A CN 106083960A
- Authority
- CN
- China
- Prior art keywords
- taxoids
- carcinoma
- hydroxyl
- cancer
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
- -1 alkyl chloroformate Chemical compound 0.000 claims abstract description 19
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 10
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 10
- 201000008275 breast carcinoma Diseases 0.000 claims abstract description 10
- 208000032839 leukemia Diseases 0.000 claims abstract description 9
- 150000008064 anhydrides Chemical class 0.000 claims abstract description 7
- 238000006482 condensation reaction Methods 0.000 claims abstract description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 7
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims abstract description 5
- 229960005277 gemcitabine Drugs 0.000 claims abstract description 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims abstract description 4
- 238000010511 deprotection reaction Methods 0.000 claims abstract description 4
- 229960003668 docetaxel Drugs 0.000 claims abstract description 4
- 230000000903 blocking effect Effects 0.000 claims abstract description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 10
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 6
- 210000001072 colon Anatomy 0.000 claims description 6
- 206010017758 gastric cancer Diseases 0.000 claims description 6
- 208000020615 rectal carcinoma Diseases 0.000 claims description 6
- 201000011549 stomach cancer Diseases 0.000 claims description 6
- 206010025323 Lymphomas Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 206010038389 Renal cancer Diseases 0.000 claims description 5
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical group C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 claims description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
- 201000010174 renal carcinoma Diseases 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical group CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims description 3
- 208000000527 Germinoma Diseases 0.000 claims description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 3
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 201000005619 esophageal carcinoma Diseases 0.000 claims description 3
- 201000003115 germ cell cancer Diseases 0.000 claims description 3
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical group O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
- 208000018389 neoplasm of cerebral hemisphere Diseases 0.000 claims description 3
- 208000025189 neoplasm of testis Diseases 0.000 claims description 3
- 201000001514 prostate carcinoma Diseases 0.000 claims description 3
- 201000000849 skin cancer Diseases 0.000 claims description 3
- 201000008261 skin carcinoma Diseases 0.000 claims description 3
- 201000003120 testicular cancer Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 229940041181 antineoplastic drug Drugs 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
- 239000003223 protective agent Substances 0.000 claims description 2
- 208000012991 uterine carcinoma Diseases 0.000 claims description 2
- 239000005046 Chlorosilane Substances 0.000 claims 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 5
- 231100000419 toxicity Toxicity 0.000 abstract description 4
- 230000001988 toxicity Effects 0.000 abstract description 4
- 125000006007 trichloroethoxy group Chemical group 0.000 abstract description 4
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 abstract description 3
- 230000001629 suppression Effects 0.000 abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 241001465754 Metazoa Species 0.000 description 31
- 239000000203 mixture Substances 0.000 description 20
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 19
- 239000012046 mixed solvent Substances 0.000 description 17
- 239000000376 reactant Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 229960004756 ethanol Drugs 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- 238000001291 vacuum drying Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 239000008389 polyethoxylated castor oil Substances 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940073561 hexamethyldisiloxane Drugs 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 231100000682 maximum tolerated dose Toxicity 0.000 description 3
- 239000011435 rock Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 244000131522 Citrus pyriformis Species 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- PLZNPHDJGFDNRM-UHFFFAOYSA-M O.[Na+].[O-][PH2]=O Chemical compound O.[Na+].[O-][PH2]=O PLZNPHDJGFDNRM-UHFFFAOYSA-M 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- JPSKCQCQZUGWNM-UHFFFAOYSA-N 2,7-Oxepanedione Chemical compound O=C1CCCCC(=O)O1 JPSKCQCQZUGWNM-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- BBZAFZZUHAKUAU-UHFFFAOYSA-N 5-carbonochloridoyloxy-5-oxopentanoic acid Chemical compound C(CC(=O)O)CC(=O)OC(=O)Cl BBZAFZZUHAKUAU-UHFFFAOYSA-N 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 0.000 description 1
- 208000008720 Bone Marrow Neoplasms Diseases 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- RMOUBSOVHSONPZ-UHFFFAOYSA-N Isopropyl formate Chemical compound CC(C)OC=O RMOUBSOVHSONPZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- DXRFZHILMCWCNG-UHFFFAOYSA-N N,N-dimethyl-1,8-naphthyridin-2-amine Chemical compound C1=CC=NC2=NC(N(C)C)=CC=C21 DXRFZHILMCWCNG-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
- 239000004698 Polyethylene Substances 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 208000008630 Sialorrhea Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 201000006491 bone marrow cancer Diseases 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- MXOSTENCGSDMRE-UHFFFAOYSA-N butyl-chloro-dimethylsilane Chemical compound CCCC[Si](C)(C)Cl MXOSTENCGSDMRE-UHFFFAOYSA-N 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- YGZSVWMBUCGDCV-UHFFFAOYSA-N chloro(methyl)silane Chemical compound C[SiH2]Cl YGZSVWMBUCGDCV-UHFFFAOYSA-N 0.000 description 1
- AVDUEHWPPXIAEB-UHFFFAOYSA-N chloro-ethyl-dimethylsilane Chemical compound CC[Si](C)(C)Cl AVDUEHWPPXIAEB-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 238000000990 heteronuclear single quantum coherence spectrum Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000009191 jumping Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- DKXULEFCEORBJK-UHFFFAOYSA-N magnesium;octadecanoic acid Chemical compound [Mg].CCCCCCCCCCCCCCCCCC(O)=O DKXULEFCEORBJK-UHFFFAOYSA-N 0.000 description 1
- 229960002160 maltose Drugs 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical class C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
实施例编号 | 化合物编号 | 氯甲酸烷基酯 | 二酸酐 | R1 | n |
实施例1 | Z1 | 氯甲酸正丁酯 | 戊二酸酐 | 正丁基 | 1 |
实施例2 | Z2 | 氯甲酸正丁酯 | 己二酸酐 | 正丁基 | 2 |
实施例3 | Z3 | 氯甲酸正丁酯 | 丁二酸酐 | 正丁基 | 0 |
实施例4 | Z4 | 氯甲酸正己酯 | 戊二酸酐 | 正己基 | 1 |
实施例5 | Z5 | 氯甲酸正己酯 | 己二酸酐 | 正己基 | 2 |
实施例6 | Z6 | 氯甲酸正己酯 | 丁二酸酐 | 正己基 | 0 |
实施例7 | Z7 | 氯甲酸乙酯 | 戊二酸酐 | 乙基 | 1 |
实施例8 | Z8 | 氯甲酸乙酯 | 己二酸酐 | 乙基 | 2 |
实施例9 | Z9 | 氯甲酸乙酯 | 丁二酸酐 | 乙基 | 0 |
Claims (10)
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610426133.4A CN106083960B (zh) | 2016-06-15 | 2016-06-15 | 新型紫杉类化合物及其制备方法和应用 |
EP16905300.6A EP3470403B1 (en) | 2016-06-15 | 2016-11-14 | Taxoid compound and preparation method and use thereof |
PCT/CN2016/105692 WO2017215188A1 (zh) | 2016-06-15 | 2016-11-14 | 新型紫杉类化合物及其制备方法和应用 |
JP2018565744A JP6801011B2 (ja) | 2016-06-15 | 2016-11-14 | 新しいタイプのタキサン化合物、その製造方法および適用 |
US16/310,403 US10676497B2 (en) | 2016-06-15 | 2016-11-14 | Type of taxane compound, preparation method and application thereof |
CA3043895A CA3043895C (en) | 2016-06-15 | 2016-11-14 | New type of taxane compound, preparation method and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610426133.4A CN106083960B (zh) | 2016-06-15 | 2016-06-15 | 新型紫杉类化合物及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106083960A true CN106083960A (zh) | 2016-11-09 |
CN106083960B CN106083960B (zh) | 2019-06-25 |
Family
ID=57236657
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610426133.4A Active CN106083960B (zh) | 2016-06-15 | 2016-06-15 | 新型紫杉类化合物及其制备方法和应用 |
Country Status (6)
Country | Link |
---|---|
US (1) | US10676497B2 (zh) |
EP (1) | EP3470403B1 (zh) |
JP (1) | JP6801011B2 (zh) |
CN (1) | CN106083960B (zh) |
CA (1) | CA3043895C (zh) |
WO (1) | WO2017215188A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109762042A (zh) * | 2018-09-21 | 2019-05-17 | 河北艾克美冀生物科技有限公司 | 一种治疗癌症的药物、其合成方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101715342A (zh) * | 2007-03-19 | 2010-05-26 | 因弗拉布洛克制药公司 | 钴胺素紫杉烷生物结合物 |
CN102264396A (zh) * | 2008-10-07 | 2011-11-30 | 瑞沙恩医药公司 | Hpma-多西他赛或吉西他滨缀合物及其用途 |
WO2012004005A1 (en) * | 2010-07-09 | 2012-01-12 | Fresenius Kabi Deutschland Gmbh | Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation |
CN103002891A (zh) * | 2010-05-10 | 2013-03-27 | 加利福尼亚大学董事会 | 比例计量型组合药物递送 |
-
2016
- 2016-06-15 CN CN201610426133.4A patent/CN106083960B/zh active Active
- 2016-11-14 CA CA3043895A patent/CA3043895C/en active Active
- 2016-11-14 US US16/310,403 patent/US10676497B2/en active Active
- 2016-11-14 EP EP16905300.6A patent/EP3470403B1/en active Active
- 2016-11-14 JP JP2018565744A patent/JP6801011B2/ja active Active
- 2016-11-14 WO PCT/CN2016/105692 patent/WO2017215188A1/zh unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101715342A (zh) * | 2007-03-19 | 2010-05-26 | 因弗拉布洛克制药公司 | 钴胺素紫杉烷生物结合物 |
CN102264396A (zh) * | 2008-10-07 | 2011-11-30 | 瑞沙恩医药公司 | Hpma-多西他赛或吉西他滨缀合物及其用途 |
CN103002891A (zh) * | 2010-05-10 | 2013-03-27 | 加利福尼亚大学董事会 | 比例计量型组合药物递送 |
WO2012004005A1 (en) * | 2010-07-09 | 2012-01-12 | Fresenius Kabi Deutschland Gmbh | Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109762042A (zh) * | 2018-09-21 | 2019-05-17 | 河北艾克美冀生物科技有限公司 | 一种治疗癌症的药物、其合成方法和应用 |
CN109762042B (zh) * | 2018-09-21 | 2022-04-08 | 河北艾克美冀生物科技有限公司 | 一种治疗癌症的药物、其合成方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
US10676497B2 (en) | 2020-06-09 |
CN106083960B (zh) | 2019-06-25 |
EP3470403A4 (en) | 2019-06-12 |
JP6801011B2 (ja) | 2020-12-16 |
EP3470403A1 (en) | 2019-04-17 |
EP3470403B1 (en) | 2020-10-07 |
CA3043895C (en) | 2020-06-09 |
CA3043895A1 (en) | 2017-12-21 |
WO2017215188A1 (zh) | 2017-12-21 |
JP2019524654A (ja) | 2019-09-05 |
US20190256545A1 (en) | 2019-08-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP3260463B1 (en) | Deuterated chenodeoxycholic acid derivative and pharmaceutical composition comprising compound thereof | |
US7691827B2 (en) | Amide prodrug of gemcitabine, compositions and use thereof | |
EP3210992B1 (en) | New type of cytidine derivative and application thereof | |
WO2009043296A1 (fr) | Dérivés et analogues de glycoside gambogique, procédé de préparation et utilisation de ceux-ci | |
US9533049B2 (en) | Method for preparing nanoparticles based on functional amphiphilic molecules or macromolecules, and the use thereof | |
CN103044395B (zh) | 含有地氯雷他定结构的氨基酸类衍生物、其制备方法和用途 | |
US10874740B2 (en) | 5-ALA derivatives and use thereof | |
CN103374015A (zh) | 喜树碱衍生物、其制备方法及其在制备治疗肿瘤药物中的应用 | |
ES2959891T3 (es) | Producción de trans-[tetraclorobis(1H-indazol)rutenato (III)] y composiciones del mismo | |
EP2043653B1 (en) | Crystalline forms of gemcitabine amide prodrug, compositions and use thereof | |
CN106083960B (zh) | 新型紫杉类化合物及其制备方法和应用 | |
CN108290920B (zh) | 5-氮杂胞苷或2’-脱氧-5-氮杂胞苷的5’-二苄基磷酸酯 | |
CN101402667A (zh) | 糖基化修饰的一氧化氮供体型齐墩果酸类化合物、其制备方法及用途 | |
CN102786458B (zh) | 吡咯甲酰胺衍生物、其制备方法和用途 | |
CN110418798B (zh) | 具有抗癌活性的甾体皂苷 | |
WO2011147254A1 (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 | |
CN105541696A (zh) | 一种抗肿瘤的化合物及其制备方法和应用 | |
US9969766B2 (en) | 20(R)-ginsenoside Rg3 polyacylated derivatives, preparation and application thereof | |
CN104098594A (zh) | 生物素-鬼臼毒素酯化衍生物及其药物组合物和其制备方法与应用 | |
JPH04210995A (ja) | 5−fu誘導体 | |
CN105949277A (zh) | 一种抗肿瘤化合物及其用途 | |
WO1991012259A1 (en) | 5-fu derivative |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB02 | Change of applicant information |
Address after: 024000, the Inner Mongolia Autonomous Region Chifeng resource-based urban economic transformation and development pilot area employment guidance and entrepreneurship Service Center Building Applicant after: INNER MONGOLIA PUYIN PHARMACEUTICAL Co.,Ltd. Address before: 024000, the Inner Mongolia Autonomous Region Chifeng resource-based urban economic transformation and development pilot area employment guidance and entrepreneurship Service Center Building Applicant before: Inner Mongolia Puyin Pharmaceutical Technology Co.,Ltd. |
|
CB02 | Change of applicant information | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20170509 Address after: 213022 Jiangsu city of Changzhou province Hehai Road New District No. 108 Applicant after: CHANGZHOU FANGYUAN PHARMACEUTICAL Co.,Ltd. Applicant after: INNER MONGOLIA PUYIN PHARMACEUTICAL Co.,Ltd. Address before: 024000, the Inner Mongolia Autonomous Region Chifeng resource-based urban economic transformation and development pilot area employment guidance and entrepreneurship Service Center Building Applicant before: INNER MONGOLIA PUYIN PHARMACEUTICAL Co.,Ltd. |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Novel yew compound and preparing method and application thereof Effective date of registration: 20200322 Granted publication date: 20190625 Pledgee: Agricultural Bank of China Limited Chifeng Yuanbaoshan sub branch Pledgor: CHANGZHOU FANGYUAN PHARMACEUTICAL Co.,Ltd.|INNER MONGOLIA PUYIN PHARMACEUTICAL Co.,Ltd. Registration number: Y2020150000009 |
|
PP01 | Preservation of patent right |
Effective date of registration: 20220310 Granted publication date: 20190625 |
|
PP01 | Preservation of patent right |