CN1246323C - 氮基喜树碱衍生物 - Google Patents
氮基喜树碱衍生物 Download PDFInfo
- Publication number
- CN1246323C CN1246323C CNB028090543A CN02809054A CN1246323C CN 1246323 C CN1246323 C CN 1246323C CN B028090543 A CNB028090543 A CN B028090543A CN 02809054 A CN02809054 A CN 02809054A CN 1246323 C CN1246323 C CN 1246323C
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- China
- Prior art keywords
- cpt
- compound
- amino
- hydroxy
- lower alkyl
- Prior art date
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- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 title abstract description 355
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title description 10
- 229910052757 nitrogen Inorganic materials 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 158
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 44
- 201000011510 cancer Diseases 0.000 claims abstract description 25
- -1 cyano, nitro, amino Chemical group 0.000 claims description 150
- 125000000217 alkyl group Chemical group 0.000 claims description 108
- 125000003545 alkoxy group Chemical group 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 26
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 26
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 26
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 19
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 241001465754 Metazoa Species 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 229920002554 vinyl polymer Polymers 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 5
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical group [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 239000007822 coupling agent Substances 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- BQIKRTGTPBOIMK-UHFFFAOYSA-N [O]C[O] Chemical compound [O]C[O] BQIKRTGTPBOIMK-UHFFFAOYSA-N 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 229940127093 camptothecin Drugs 0.000 abstract description 420
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 abstract description 404
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 abstract description 404
- 239000002253 acid Substances 0.000 abstract description 18
- 238000011282 treatment Methods 0.000 abstract description 17
- 150000002148 esters Chemical class 0.000 abstract description 12
- 150000007513 acids Chemical class 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 43
- 239000007787 solid Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 32
- 239000000126 substance Substances 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 28
- 230000015572 biosynthetic process Effects 0.000 description 28
- 229920006395 saturated elastomer Polymers 0.000 description 27
- 235000017557 sodium bicarbonate Nutrition 0.000 description 27
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 26
- 238000004458 analytical method Methods 0.000 description 26
- 238000003786 synthesis reaction Methods 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 25
- 235000019260 propionic acid Nutrition 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 22
- 150000003254 radicals Chemical class 0.000 description 22
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- DGHHQBMTXTWTJV-BQAIUKQQSA-N 119413-54-6 Chemical compound Cl.C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 DGHHQBMTXTWTJV-BQAIUKQQSA-N 0.000 description 17
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 17
- 229960000303 topotecan Drugs 0.000 description 17
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 16
- XLHNAFUKOSPOAT-UHFFFAOYSA-N 4-ethyl-4-hydroxy-9-nitro-(+-)-1h-pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4h,12h)-dione Chemical compound C1=C([N+]([O-])=O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 XLHNAFUKOSPOAT-UHFFFAOYSA-N 0.000 description 15
- FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 150000002431 hydrogen Chemical group 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
- 231100000419 toxicity Toxicity 0.000 description 13
- 230000001988 toxicity Effects 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 12
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 10
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 9
- 125000000623 heterocyclic group Chemical group 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 230000002427 irreversible effect Effects 0.000 description 7
- OKMRLRFCLKDMTG-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-ium-1-yl)propanoate Chemical compound C1CN(CCC(=O)O)CCN1CC1=CC=CC=C1 OKMRLRFCLKDMTG-UHFFFAOYSA-N 0.000 description 6
- JUXGOBSASOVDKO-UHFFFAOYSA-N 3-(4-phenylpiperazin-1-ium-1-yl)propanoate Chemical compound C1CN(CCC(=O)O)CCN1C1=CC=CC=C1 JUXGOBSASOVDKO-UHFFFAOYSA-N 0.000 description 6
- BHTCICYNHHCUFK-UHFFFAOYSA-N 3-[4-(2-chlorophenyl)piperazin-1-ium-1-yl]propanoate Chemical compound C1CN(CCC(=O)O)CCN1C1=CC=CC=C1Cl BHTCICYNHHCUFK-UHFFFAOYSA-N 0.000 description 6
- OJEVCLMHRBHIKC-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)piperazin-1-ium-1-yl]propanoate Chemical compound C1CN(CCC(=O)O)CCN1C1=CC=C(F)C=C1 OJEVCLMHRBHIKC-UHFFFAOYSA-N 0.000 description 6
- FPEXVEVOZJTVAG-UHFFFAOYSA-N 3-[4-(4-nitrophenyl)piperazin-1-ium-1-yl]propanoate Chemical compound C1CN(CCC(=O)O)CCN1C1=CC=C([N+]([O-])=O)C=C1 FPEXVEVOZJTVAG-UHFFFAOYSA-N 0.000 description 6
- GDTCVEVTIDTQKL-UHFFFAOYSA-N 3-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]propanoic acid Chemical compound C1CN(CCC(=O)O)CCN1C1=CC=CC(C(F)(F)F)=C1 GDTCVEVTIDTQKL-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- VJQUTRDUXKPESF-UHFFFAOYSA-N 3-[4-(3-methoxyphenyl)piperazin-1-ium-1-yl]propanoate Chemical compound COC1=CC=CC(N2CCN(CCC(O)=O)CC2)=C1 VJQUTRDUXKPESF-UHFFFAOYSA-N 0.000 description 5
- JHOUSXWICJCPBA-UHFFFAOYSA-N 3-[4-(4-acetylphenyl)piperazin-1-yl]propanoic acid Chemical compound C1=CC(C(=O)C)=CC=C1N1CCN(CCC(O)=O)CC1 JHOUSXWICJCPBA-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
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- 210000001519 tissue Anatomy 0.000 description 5
- DXXHRZUOTPMGEH-UHFFFAOYSA-N 3-(1,3-dioxoisoindol-2-yl)propanoic acid Chemical compound C1=CC=C2C(=O)N(CCC(=O)O)C(=O)C2=C1 DXXHRZUOTPMGEH-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
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- FBDOJYYTMIHHDH-OZBJMMHXSA-N (19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-2,4,6,8,10,14,20-heptaen-18-one Chemical compound CC[C@@]1(O)C(=O)OCC2=CN3Cc4cc5ccccc5nc4C3C=C12 FBDOJYYTMIHHDH-OZBJMMHXSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000003915 DNA Topoisomerases Human genes 0.000 description 3
- 108090000323 DNA Topoisomerases Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010015548 Euthanasia Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 208000009956 adenocarcinoma Diseases 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 239000004599 antimicrobial Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
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- 150000001721 carbon Chemical group 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
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- 230000003211 malignant effect Effects 0.000 description 3
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- 229910052717 sulfur Inorganic materials 0.000 description 3
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- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- KKIMDKMETPPURN-UHFFFAOYSA-N 1-(3-(trifluoromethyl)phenyl)piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=C1 KKIMDKMETPPURN-UHFFFAOYSA-N 0.000 description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- DUAWRLXHCUAWMK-UHFFFAOYSA-N 2-iminiopropionate Chemical compound CC(=[NH2+])C([O-])=O DUAWRLXHCUAWMK-UHFFFAOYSA-N 0.000 description 2
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- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical class CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
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- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 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 2
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- 230000000259 anti-tumor effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
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- 230000005907 cancer growth Effects 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
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- 150000002596 lactones Chemical class 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
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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
- C07D491/22—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 four or more hetero rings
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/797,765 US6403604B1 (en) | 2001-03-01 | 2001-03-01 | Nitrogen-based camptothecin derivatives |
| US09/797,765 | 2001-03-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1511159A CN1511159A (zh) | 2004-07-07 |
| CN1246323C true CN1246323C (zh) | 2006-03-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB028090543A Expired - Fee Related CN1246323C (zh) | 2001-03-01 | 2002-02-06 | 氮基喜树碱衍生物 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6403604B1 (enExample) |
| EP (1) | EP1383772B1 (enExample) |
| JP (1) | JP4584538B2 (enExample) |
| KR (1) | KR100853141B1 (enExample) |
| CN (1) | CN1246323C (enExample) |
| AT (1) | ATE338047T1 (enExample) |
| CA (1) | CA2439787C (enExample) |
| DE (1) | DE60214359T2 (enExample) |
| ES (1) | ES2274020T3 (enExample) |
| IL (2) | IL157669A0 (enExample) |
| MX (1) | MXPA03007896A (enExample) |
| NZ (1) | NZ528115A (enExample) |
| WO (1) | WO2002070525A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12029736B2 (en) | 2020-02-25 | 2024-07-09 | Mediboston Limited | Camptothecin derivatives and conjugates thereof |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6150343A (en) * | 1993-06-30 | 2000-11-21 | University Of Pittsburgh | Camptothecin analogs and methods of preparation thereof |
| US6492380B1 (en) * | 1999-05-17 | 2002-12-10 | Queen's University At Kingston | Method of inhibiting neurotrophin-receptor binding |
| US6350756B1 (en) | 2001-01-18 | 2002-02-26 | California Pacific Medical Center | Camptothecin derivatives |
| US6855720B2 (en) * | 2001-03-01 | 2005-02-15 | California Pacific Medical Center | Nitrogen-based camptothecin derivatives |
| US6403604B1 (en) * | 2001-03-01 | 2002-06-11 | California Pacific Medical Center | Nitrogen-based camptothecin derivatives |
| WO2003101998A1 (en) * | 2002-06-03 | 2003-12-11 | California Pacific Medical Center | Nitrogen-based homo-camptothecin derivatives |
| US20040034050A1 (en) * | 2002-06-03 | 2004-02-19 | Yang Li-Xi | Homo-camptothecin derivatives |
| FR2889528B1 (fr) * | 2005-08-05 | 2007-09-07 | Servier Lab | Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2889527A1 (fr) * | 2005-08-05 | 2007-02-09 | Servier Lab | Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| KR20080058403A (ko) | 2005-09-15 | 2008-06-25 | 페인셉터 파마 코포레이션 | 뉴로트로핀 매개 활성 조절 방법 |
| US7875602B2 (en) * | 2005-10-21 | 2011-01-25 | Sutter West Bay Hospitals | Camptothecin derivatives as chemoradiosensitizing agents |
| CN100586952C (zh) * | 2006-11-10 | 2010-02-03 | 中国药科大学 | 噁唑骈喜树碱酯衍生物及其制备方法和用途 |
| WO2009089537A2 (en) | 2008-01-11 | 2009-07-16 | Northwestern University | Anti-cancer compounds |
| CN104622809B (zh) * | 2008-05-23 | 2019-04-19 | 英属哥伦比亚大学 | 用于脂质体纳米颗粒的修饰的药物 |
| CN102574866B (zh) * | 2009-06-17 | 2015-02-18 | 四川恒康发展有限责任公司 | 喜树碱衍生物 |
| IN2014DN00277A (enExample) | 2011-11-03 | 2015-06-05 | Taiwan Liposome Co Ltd | |
| US10980798B2 (en) | 2011-11-03 | 2021-04-20 | Taiwan Liposome Company, Ltd. | Pharmaceutical compositions of hydrophobic camptothecin derivatives |
| CN109575044A (zh) * | 2018-12-21 | 2019-04-05 | 西安交通大学 | 2-（喜树碱-10-氧基）乙酰胺类化合物和应用 |
| JP7210770B2 (ja) * | 2019-03-29 | 2023-01-23 | メドイミューン・リミテッド | 化合物及びその複合体 |
| KR20250079213A (ko) | 2022-10-09 | 2025-06-04 | 라노바 메디신즈 리미티드 | 화합물, 조성물 및 방법 |
| CN117285540B (zh) * | 2023-09-27 | 2025-07-11 | 中国海洋大学 | 12-位取代的喜树碱衍生物及其用途 |
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|---|---|---|---|---|
| US4943579A (en) | 1987-10-06 | 1990-07-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Water soluble prodrugs of camptothecin |
| GB9320781D0 (en) | 1993-10-08 | 1993-12-01 | Erba Carlo Spa | Polymer-bound camptothecin derivatives |
| US5965566A (en) * | 1993-10-20 | 1999-10-12 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
| US5919455A (en) | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5646159A (en) | 1994-07-20 | 1997-07-08 | Research Triangle Institute | Water-soluble esters of camptothecin compounds |
| GB9504065D0 (en) | 1995-03-01 | 1995-04-19 | Pharmacia Spa | Poly-pyrrolecarboxamidonaphthalenic acid derivatives |
| JPH08333370A (ja) * | 1995-06-08 | 1996-12-17 | Kyorin Pharmaceut Co Ltd | 水に可溶な新規フルオロエチルカンプトテシン誘導体、及びその製造方法 |
| US6339091B1 (en) * | 1995-06-21 | 2002-01-15 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Comptothecin analogues, preparation methods therefor, use thereof as drugs, and pharmaceutical compositions containing said analogues |
| AU7732996A (en) | 1995-11-22 | 1997-06-11 | Research Triangle Institute | Camptothecin compounds with combined topoisomerase i inhibition and dna alkylation properties |
| US6096336A (en) | 1996-01-30 | 2000-08-01 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
| US5731316A (en) | 1996-01-30 | 1998-03-24 | The Stehlin Foundation For Cancer Research | Derivatives of camptothecin and methods of treating cancer using these derivatives |
| DE69728152T2 (de) | 1996-08-19 | 2004-08-05 | Bionumerik Pharmaceuticals, Inc., San Antonio | Hoch-lipophile campothecin-derivate |
| EP0961619A4 (en) | 1996-09-27 | 2001-09-26 | Bristol Myers Squibb Co | HYDROLYSABLE DRUGS FOR THE RELEASE OF ANTI-CANCER DRUGS IN METASTATIC CELLS |
| ATE210673T1 (de) | 1996-09-30 | 2001-12-15 | Bayer Ag | Glycokonjugate von modifizierten camptothecin- derivaten (20-o-verknüpfung) |
| SG103322A1 (en) | 1996-10-30 | 2004-04-29 | Tanabe Seiyaku Co | S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds and process for preparation thereof |
| UA57757C2 (uk) | 1996-12-20 | 2003-07-15 | Сос'Єте Де Консей Де Решерш Е Даплікасьон С'Єнтіфік (С.К.Р.А.С.) | Аналоги камптотецину, спосіб їх отримання (варіанти) і фармацевтична композиція |
| ID23424A (id) | 1997-05-14 | 2000-04-20 | Bayer Ag | Glikokonjugat dari 20(s)-kamptotesin |
| GB9721070D0 (en) | 1997-10-03 | 1997-12-03 | Pharmacia & Upjohn Spa | Bioactive derivatives of camptothecin |
| US6153655A (en) | 1998-04-17 | 2000-11-28 | Enzon, Inc. | Terminally-branched polymeric linkers and polymeric conjugates containing the same |
| US6057303A (en) | 1998-10-20 | 2000-05-02 | Bionumerik Pharmaceuticals, Inc. | Highly lipophilic Camptothecin derivatives |
| US6207832B1 (en) * | 1999-04-09 | 2001-03-27 | University Of Pittsburgh | Camptothecin analogs and methods of preparation thereof |
| AU4822500A (en) | 1999-05-04 | 2000-11-17 | Bionumerik Pharmaceuticals, Inc. | Novel highly lipophilic camptothecin analogs |
| US6765019B1 (en) | 1999-05-06 | 2004-07-20 | University Of Kentucky Research Foundation | Permeable, water soluble, non-irritating prodrugs of chemotherapeutic agents with oxaalkanoic acids |
| US6288072B1 (en) * | 1999-12-29 | 2001-09-11 | Monroe E. Wall | Camptothecin β-alanine esters with topoisomerase I inhibition |
| US6350756B1 (en) * | 2001-01-18 | 2002-02-26 | California Pacific Medical Center | Camptothecin derivatives |
| US6403604B1 (en) * | 2001-03-01 | 2002-06-11 | California Pacific Medical Center | Nitrogen-based camptothecin derivatives |
| GB0119578D0 (en) | 2001-08-10 | 2001-10-03 | Pharmacia & Upjohn Spa | Fluoro linkers |
-
2001
- 2001-03-01 US US09/797,765 patent/US6403604B1/en not_active Expired - Lifetime
-
2002
- 2002-02-06 JP JP2002569845A patent/JP4584538B2/ja not_active Expired - Fee Related
- 2002-02-06 ES ES02718930T patent/ES2274020T3/es not_active Expired - Lifetime
- 2002-02-06 NZ NZ528115A patent/NZ528115A/en not_active IP Right Cessation
- 2002-02-06 EP EP02718930A patent/EP1383772B1/en not_active Expired - Lifetime
- 2002-02-06 MX MXPA03007896A patent/MXPA03007896A/es active IP Right Grant
- 2002-02-06 KR KR1020037011466A patent/KR100853141B1/ko not_active Expired - Fee Related
- 2002-02-06 CA CA2439787A patent/CA2439787C/en not_active Expired - Fee Related
- 2002-02-06 AT AT02718930T patent/ATE338047T1/de not_active IP Right Cessation
- 2002-02-06 IL IL15766902A patent/IL157669A0/xx unknown
- 2002-02-06 DE DE60214359T patent/DE60214359T2/de not_active Expired - Lifetime
- 2002-02-06 WO PCT/US2002/003798 patent/WO2002070525A2/en not_active Ceased
- 2002-02-06 CN CNB028090543A patent/CN1246323C/zh not_active Expired - Fee Related
- 2002-05-23 US US10/154,768 patent/US6825207B2/en not_active Expired - Fee Related
-
2003
- 2003-08-31 IL IL157669A patent/IL157669A/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12029736B2 (en) | 2020-02-25 | 2024-07-09 | Mediboston Limited | Camptothecin derivatives and conjugates thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004529114A (ja) | 2004-09-24 |
| KR100853141B1 (ko) | 2008-08-20 |
| JP4584538B2 (ja) | 2010-11-24 |
| CN1511159A (zh) | 2004-07-07 |
| WO2002070525A3 (en) | 2003-02-20 |
| US6825207B2 (en) | 2004-11-30 |
| DE60214359D1 (en) | 2006-10-12 |
| ES2274020T3 (es) | 2007-05-16 |
| IL157669A (en) | 2010-11-30 |
| IL157669A0 (en) | 2004-03-28 |
| ATE338047T1 (de) | 2006-09-15 |
| KR20040002872A (ko) | 2004-01-07 |
| WO2002070525A2 (en) | 2002-09-12 |
| CA2439787A1 (en) | 2002-09-12 |
| MXPA03007896A (es) | 2004-06-07 |
| CA2439787C (en) | 2011-05-24 |
| EP1383772B1 (en) | 2006-08-30 |
| US20030073698A1 (en) | 2003-04-17 |
| EP1383772A2 (en) | 2004-01-28 |
| NZ528115A (en) | 2006-04-28 |
| US6403604B1 (en) | 2002-06-11 |
| DE60214359T2 (de) | 2007-08-30 |
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