CN1318426C - 新型的斑蝥胺和去甲斑蝥胺衍生物及其在医药中的应用 - Google Patents
新型的斑蝥胺和去甲斑蝥胺衍生物及其在医药中的应用 Download PDFInfo
- Publication number
- CN1318426C CN1318426C CNB200480005763XA CN200480005763A CN1318426C CN 1318426 C CN1318426 C CN 1318426C CN B200480005763X A CNB200480005763X A CN B200480005763XA CN 200480005763 A CN200480005763 A CN 200480005763A CN 1318426 C CN1318426 C CN 1318426C
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- conjugate
- group
- amino acid
- 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.)
- Expired - Fee Related
Links
- 239000003814 drug Substances 0.000 title claims description 9
- UCMLAGLRLOPBAX-PRRDBKRISA-N (3as,4r,7s,7ar)-3a,7a-dimethyl-2-[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]-4,5,6,7-tetrahydro-octahydro-1h-4,7-epoxyisoindole-1,3-dione Chemical compound C1=C(OC(F)(F)F)C=C2SC(N3C(=O)[C@]4(C)[C@H]5CC[C@H](O5)[C@@]4(C3=O)C)=NC2=C1 UCMLAGLRLOPBAX-PRRDBKRISA-N 0.000 title description 7
- 241001597008 Nomeidae Species 0.000 title 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 30
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 46
- JAABVEXCGCXWRR-FBXFSONDSA-N rel-norcantharidin Chemical compound C1C[C@H]2[C@@H]3C(=O)OC(=O)[C@@H]3[C@@H]1O2 JAABVEXCGCXWRR-FBXFSONDSA-N 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- -1 methoxyethyl Chemical group 0.000 claims description 19
- 150000001413 amino acids Chemical class 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 230000000259 anti-tumor effect Effects 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229920003169 water-soluble polymer Polymers 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 230000000118 anti-neoplastic effect Effects 0.000 claims 3
- 238000009472 formulation Methods 0.000 claims 2
- ARXKVVRQIIOZGF-UHFFFAOYSA-N 1,2,4-butanetriol Chemical compound OCCC(O)CO ARXKVVRQIIOZGF-UHFFFAOYSA-N 0.000 claims 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- 229940034982 antineoplastic agent Drugs 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 13
- 230000001093 anti-cancer Effects 0.000 abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- 150000001412 amines Chemical class 0.000 abstract 5
- 239000000543 intermediate Substances 0.000 abstract 4
- SWWQQSDRUYSMAR-UHFFFAOYSA-N 1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrochloride Chemical group Cl.C1=CC(O)=CC=C1CC1C2=CC(O)=C(O)C=C2CCN1 SWWQQSDRUYSMAR-UHFFFAOYSA-N 0.000 abstract 3
- 125000003368 amide group Chemical group 0.000 abstract 1
- 229920000151 polyglycol Polymers 0.000 abstract 1
- 239000010695 polyglycol Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 26
- 239000002202 Polyethylene glycol Substances 0.000 description 23
- 229920001223 polyethylene glycol Polymers 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- 229930008397 cantharidin Natural products 0.000 description 16
- 229940095758 cantharidin Drugs 0.000 description 16
- DHZBEENLJMYSHQ-UHFFFAOYSA-N cantharidine Natural products O1C2CCC1C1(C)C2(C)C(=O)OC1=O DHZBEENLJMYSHQ-UHFFFAOYSA-N 0.000 description 16
- DHZBEENLJMYSHQ-XCVPVQRUSA-N cantharidin Chemical compound C([C@@H]1O2)C[C@@H]2[C@]2(C)[C@@]1(C)C(=O)OC2=O DHZBEENLJMYSHQ-XCVPVQRUSA-N 0.000 description 15
- 235000001014 amino acid Nutrition 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000003710 aryl alkyl group Chemical group 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 125000004404 heteroalkyl group Chemical group 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 231100000331 toxic Toxicity 0.000 description 9
- 230000002588 toxic effect Effects 0.000 description 9
- 238000002390 rotary evaporation Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 150000002334 glycols Chemical class 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- WUQNOBSCYAIJIH-FIPCFZRWSA-N (3as,4r,7s,7ar)-2,3a,7a-trimethyl-4,5,6,7-tetrahydro-octahydro-1h-4,7-epoxyisoindole-1,3-dione Chemical compound C([C@@H]1O2)C[C@@H]2[C@]2(C)[C@@]1(C)C(=O)N(C)C2=O WUQNOBSCYAIJIH-FIPCFZRWSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 241000124079 Mylabris Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 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 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical compound NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 241000283090 Elephantidae Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108050008598 Phosphoesterases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- VIBDJEWPNNCFQO-UHFFFAOYSA-N ethane-1,1,2-triol Chemical compound OCC(O)O VIBDJEWPNNCFQO-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 229930003658 monoterpene Natural products 0.000 description 1
- 150000002773 monoterpene derivatives Chemical class 0.000 description 1
- 235000002577 monoterpenes Nutrition 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims (29)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNA200310116882XA CN1623993A (zh) | 2003-12-02 | 2003-12-02 | 新型的斑蝥胺和去甲斑蝥胺衍生物及其在医药中的应用 |
CN200310116882.X | 2003-12-02 | ||
PCT/CN2004/001399 WO2005054251A1 (fr) | 2003-12-02 | 2004-12-02 | Nouvelle amine cartharidique, derives demethyle de l'amine cartharidique et leur utilisation a des fins medicinales |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1756758A CN1756758A (zh) | 2006-04-05 |
CN1318426C true CN1318426C (zh) | 2007-05-30 |
Family
ID=34638040
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA200310116882XA Pending CN1623993A (zh) | 2003-12-02 | 2003-12-02 | 新型的斑蝥胺和去甲斑蝥胺衍生物及其在医药中的应用 |
CNB200480005763XA Expired - Fee Related CN1318426C (zh) | 2003-12-02 | 2004-12-02 | 新型的斑蝥胺和去甲斑蝥胺衍生物及其在医药中的应用 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA200310116882XA Pending CN1623993A (zh) | 2003-12-02 | 2003-12-02 | 新型的斑蝥胺和去甲斑蝥胺衍生物及其在医药中的应用 |
Country Status (2)
Country | Link |
---|---|
CN (2) | CN1623993A (zh) |
WO (1) | WO2005054251A1 (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014114262A1 (zh) * | 2013-01-28 | 2014-07-31 | 天津键凯科技有限公司 | 水溶性聚合物-氨基酸寡肽-药物结合物及其制备方法和用途 |
US9700633B2 (en) | 2013-01-28 | 2017-07-11 | Jenkem Technology Co., Ltd., Tianjin Branch | Conjugates of water soluble polymer-amino acid oligopeptide-drug, preparation method and use thereof |
CN103483346B (zh) * | 2013-09-04 | 2016-06-22 | 西北农林科技大学 | 一种去甲斑蝥酰亚胺类衍生物及其制备方法和应用 |
CN115894510B (zh) * | 2022-12-02 | 2024-06-25 | 重庆市中药研究院 | 一种斑蝥素衍生物及其抗肝癌活性应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1050877A (zh) * | 1989-10-09 | 1991-04-24 | 北京师范大学 | 去甲斑蝥酰亚胺n-烷基衍生物合成法 |
WO2002042310A2 (en) * | 2000-11-23 | 2002-05-30 | Bayer Cropscience Ag | Oxabicyclo[2.2.1]heptane derivatives as pesticidal agents |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AUPP466598A0 (en) * | 1998-07-14 | 1998-08-06 | University Of Newcastle Research Associates Limited, The | Product and process |
AUPR392301A0 (en) * | 2001-03-23 | 2001-04-26 | University Of Newcastle Research Associates Limited, The | Protein phosphatase inhibitors |
-
2003
- 2003-12-02 CN CNA200310116882XA patent/CN1623993A/zh active Pending
-
2004
- 2004-12-02 CN CNB200480005763XA patent/CN1318426C/zh not_active Expired - Fee Related
- 2004-12-02 WO PCT/CN2004/001399 patent/WO2005054251A1/zh active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1050877A (zh) * | 1989-10-09 | 1991-04-24 | 北京师范大学 | 去甲斑蝥酰亚胺n-烷基衍生物合成法 |
WO2002042310A2 (en) * | 2000-11-23 | 2002-05-30 | Bayer Cropscience Ag | Oxabicyclo[2.2.1]heptane derivatives as pesticidal agents |
Also Published As
Publication number | Publication date |
---|---|
WO2005054251A1 (fr) | 2005-06-16 |
CN1756758A (zh) | 2006-04-05 |
CN1623993A (zh) | 2005-06-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2005092898A1 (fr) | Conjugue d'extraits de tripterydium a polymere hydrophile et leurs compositions pharmaceutiques | |
US5614549A (en) | High molecular weight polymer-based prodrugs | |
CA2208841C (en) | High molecular weight polymer-based prodrugs | |
EP1496076B1 (en) | Hydrophilic polymer derivate with y type branch and preparation method of it medical composite comprising above compound | |
US7498035B2 (en) | Compounds of hydrophilic polymer-polycarboxyl oligopeptide and medicines, medical composite comprising above compound and use of above compound in medicines | |
WO2005121181A1 (fr) | Polyethyleneglycol-oligopeptides de type branchement d'arbre multipoint et leurs derives actifs et composes | |
CN112592331A (zh) | 一种奥司他韦protac化合物及其制备方法与在抗流感病毒药物中的应用 | |
CN1318426C (zh) | 新型的斑蝥胺和去甲斑蝥胺衍生物及其在医药中的应用 | |
US20050220753A1 (en) | Hydrophilic polymers-flavoids conjugates and pharmaceutical compositions comprising them | |
CN114555607B (zh) | 一类靶向蛋白质水解通路的功能分子及其制备和应用 | |
CN103360590B (zh) | 一种甲氧基聚乙二醇-二脂肪酰磷脂酰乙醇胺的制备方法 | |
CA1212670A (en) | Water-soluble rifampicin derivatives | |
WO2005044837A1 (fr) | Conjugues d'extraits de buxus et de polymere hydrophile et compositions pharmaceutiques correspondantes | |
US20060014666A1 (en) | Targeted hydrophilic polymer, binders with interferon and medical composite comprising above binders | |
CN110124048B (zh) | 多臂聚乙二醇苦参碱缀合物、其制备方法和应用 | |
US5696154A (en) | Brefeldin A derivatives and their utility in the treatment of cancer | |
ES2198631T3 (es) | Compuestos 18beta,19beta-diacetiloxi-18alfa,19alfa-epoxi-3,13(16),14-clerodatrien-2-ona (esculentina a) y 18beta,19beta-diacetiloxi-18alfa,19alfa-epoxi-3,12,14-clerodatrien-2beta-isovaleriloxi-6beta,7alfa-diol (esculentina b), proc. preparacion, y uso en fabricacion medicamentos. | |
EP0467280B1 (en) | Novel spergualin-related compound and use thereof | |
EP0213526A1 (en) | Spergualin-related compounds, a process for their preparation and their use as medicaments | |
CN115894607A (zh) | 一种抗肿瘤的苯丙氨酸缬氨酰衍生物及其制备方法 | |
JPH01117830A (ja) | 抗サイトメガロウイルス剤 | |
JPH0687738A (ja) | 抗真菌剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Cantharides amine and demethyl cantharides amine derivative and application in medicine thereof Effective date of registration: 20110629 Granted publication date: 20070530 Pledgee: Zhongguancun Beijing science and technology Company limited by guarantee Pledgor: JENKEM TECHNOLOGY Co.,Ltd. (BEIJING)|JENKEM TECHNOLOGY Co.,Ltd. (TIANJIN) Registration number: 2011990000250 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20120607 Granted publication date: 20070530 Pledgee: Zhongguancun Beijing science and technology Company limited by guarantee Pledgor: JENKEM TECHNOLOGY Co.,Ltd. (BEIJING)|JENKEM TECHNOLOGY Co.,Ltd. (TIANJIN) Registration number: 2011990000250 |
|
CP03 | Change of name, title or address |
Address after: 100192 Beijing, Haidian District West Road, No. 66 Dongsheng science and Technology Park, building C1, floor 3 Patentee after: JENKEM TECHNOLOGY Co.,Ltd. (BEIJING) Address before: Haidian District, Beijing, China No. 2 on the road to the international information technology park C building, level Four Patentee before: JENKEM TECHNOLOGY Co.,Ltd. (BEIJING) |
|
CP03 | Change of name, title or address | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070530 Termination date: 20211202 |
|
CF01 | Termination of patent right due to non-payment of annual fee |