CA2487252C - Esters in position 20 of camptothecins - Google Patents
Esters in position 20 of camptothecins Download PDFInfo
- Publication number
- CA2487252C CA2487252C CA2487252A CA2487252A CA2487252C CA 2487252 C CA2487252 C CA 2487252C CA 2487252 A CA2487252 A CA 2487252A CA 2487252 A CA2487252 A CA 2487252A CA 2487252 C CA2487252 C CA 2487252C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- branched
- straight
- group
- camptothecin
- 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
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- 150000002148 esters Chemical group 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- 239000000203 mixture Substances 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 3
- -1 nitro, amino Chemical group 0.000 claims description 50
- 229940127093 camptothecin Drugs 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 18
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 16
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 15
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 15
- 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 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
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- 239000007983 Tris buffer Substances 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Inorganic materials [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 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 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([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
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000050 cytotoxic potential Toxicity 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 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
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 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
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000003544 oxime group Chemical group 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine 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
- C07D491/22—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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM2002A000306 | 2002-05-31 | ||
| IT2002RM000306A ITRM20020306A1 (it) | 2002-05-31 | 2002-05-31 | Esteri in posizione 20 di camptotecine. |
| PCT/IT2003/000329 WO2003101996A2 (en) | 2002-05-31 | 2003-05-28 | Esters in position 20 of camptothecins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2487252A1 CA2487252A1 (en) | 2003-12-11 |
| CA2487252C true CA2487252C (en) | 2010-08-10 |
Family
ID=11456339
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2487252A Expired - Fee Related CA2487252C (en) | 2002-05-31 | 2003-05-28 | Esters in position 20 of camptothecins |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US7452900B2 (enExample) |
| EP (2) | EP1509529B1 (enExample) |
| JP (1) | JP4593270B2 (enExample) |
| KR (1) | KR101000963B1 (enExample) |
| CN (1) | CN100376583C (enExample) |
| AR (1) | AR040140A1 (enExample) |
| AT (1) | ATE439362T1 (enExample) |
| AU (1) | AU2003241161C1 (enExample) |
| CA (1) | CA2487252C (enExample) |
| CY (2) | CY1109581T1 (enExample) |
| DE (1) | DE60328777D1 (enExample) |
| DK (2) | DK1509529T3 (enExample) |
| ES (2) | ES2331569T3 (enExample) |
| IT (1) | ITRM20020306A1 (enExample) |
| MX (1) | MXPA04011681A (enExample) |
| PE (1) | PE20040533A1 (enExample) |
| PL (1) | PL374009A1 (enExample) |
| PT (2) | PT1509529E (enExample) |
| SI (2) | SI1509529T1 (enExample) |
| TW (1) | TWI331151B (enExample) |
| WO (1) | WO2003101996A2 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2852606A1 (fr) * | 2003-03-18 | 2004-09-24 | Inst Nat Sante Rech Med | Moyens pour inhiber simultanement l'expression de plusieurs genes impliques dans une pathologie |
| CN1946421B (zh) | 2004-04-27 | 2013-07-17 | 威尔斯达特生物制剂公司 | 使用病毒和喜树碱进行的癌症治疗 |
| ITRM20040242A1 (it) * | 2004-05-13 | 2004-08-13 | Ist Naz Stud Cura Dei Tumori | "7-t-butossiimminometilcamptotecina coniugata in posizione 20 con antagonisti delle integrine. |
| RU2435586C2 (ru) | 2005-07-14 | 2011-12-10 | Веллстат Байолоджикс Корпорейшн | Лечение рака с применением вирусов, фторпиримидинов и камптотецинов |
| CN103864811A (zh) * | 2012-12-13 | 2014-06-18 | 天津科技大学 | 一种新颖的10-羟基喜树碱20位衍生物制备方法及其在抗肿瘤药物中的应用 |
| WO2014121033A1 (en) * | 2013-02-04 | 2014-08-07 | Fl Therapeutics Llc | Soluble complexes of drug analogs and albumin |
| WO2015200837A1 (en) | 2014-06-27 | 2015-12-30 | Fl Therapeutics Llc | Abiraterone derivatives and non-covalent complexes with albumin |
| WO2016065139A1 (en) | 2014-10-24 | 2016-04-28 | Fl Therapeutics Llc | 3-substituted piperidine-2, 6-diones and non-covalent complexes with albumin |
| JP6877049B2 (ja) | 2015-09-25 | 2021-05-26 | ゼットワイ セラピューティクス インク．Ｚｙ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． | 多糖類−ビタミン共役体を含む粒状物に基づく薬物製剤 |
| CN106279286B (zh) * | 2016-08-12 | 2018-11-30 | 华中科技大学 | 一种喜树碱膦酸酯类化合物、其制备方法及应用 |
| CN110577551A (zh) * | 2018-06-08 | 2019-12-17 | 遵义医学院 | 喜树碱-甘氨酸-5,6-二溴去甲斑蝥素结合物及其应用 |
| BR112022000401A2 (pt) | 2019-07-11 | 2022-03-29 | Sun Pharma Advanced Res Co Ltd | Derivados de camptotecina com uma porção dissulfeto e uma porção piperazina |
| CN116514829A (zh) * | 2020-08-21 | 2023-08-01 | 诺茗(北京)生物医药有限公司 | 一种水溶性抗肿瘤前药及其药物组合物和用途 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US5004758A (en) * | 1987-12-01 | 1991-04-02 | Smithkline Beecham Corporation | Water soluble camptothecin analogs useful for inhibiting the growth of animal tumor cells |
| JP3186166B2 (ja) * | 1992-02-10 | 2001-07-11 | ロンザ リミテッド | サリチロイル−カルニチンおよびその製造方法 |
| US5646159A (en) * | 1994-07-20 | 1997-07-08 | Research Triangle Institute | Water-soluble esters of camptothecin compounds |
| WO1997021865A1 (en) | 1995-12-15 | 1997-06-19 | The Dexter Corporation | Abrasive nonwoven web and method of manufacture |
| PT1100589E (pt) | 1998-07-30 | 2005-05-31 | Sigma Tau Ind Farmaceuti | Utilizacao de propionil-l-carnitina e acetil-l-carnitina na preparacao de medicamentos com actividade anticancerigena |
| US6204257B1 (en) | 1998-08-07 | 2001-03-20 | Universtiy Of Kansas | Water soluble prodrugs of hindered alcohols |
| PT1044977E (pt) | 1999-03-09 | 2002-09-30 | Sigma Tau Ind Farmaceuti | Derivados de camptotecina com actividade antitumoral |
| DE19916945C1 (de) | 1999-04-15 | 2000-10-05 | Clariant Gmbh | Aromatische Aldehydharze und ihre Verwendung als Emulsionsspalter |
| US6228855B1 (en) | 1999-08-03 | 2001-05-08 | The Stehlin Foundation For Cancer Research | Aromatic esters of camptothecins and methods to treat cancers |
| US6288072B1 (en) * | 1999-12-29 | 2001-09-11 | Monroe E. Wall | Camptothecin β-alanine esters with topoisomerase I inhibition |
| US6629995B1 (en) | 2000-03-31 | 2003-10-07 | Super Gen, Inc. | Camptothecin conjugates |
-
2002
- 2002-05-31 IT IT2002RM000306A patent/ITRM20020306A1/it unknown
-
2003
- 2003-05-26 TW TW092114165A patent/TWI331151B/zh not_active IP Right Cessation
- 2003-05-28 EP EP03730481A patent/EP1509529B1/en not_active Expired - Lifetime
- 2003-05-28 DK DK03730481T patent/DK1509529T3/da active
- 2003-05-28 PL PL03374009A patent/PL374009A1/xx unknown
- 2003-05-28 PT PT03730481T patent/PT1509529E/pt unknown
- 2003-05-28 ES ES03730481T patent/ES2331569T3/es not_active Expired - Lifetime
- 2003-05-28 CN CNB038125447A patent/CN100376583C/zh not_active Expired - Fee Related
- 2003-05-28 AT AT03730481T patent/ATE439362T1/de active
- 2003-05-28 SI SI200331685T patent/SI1509529T1/sl unknown
- 2003-05-28 ES ES09162737T patent/ES2432379T3/es not_active Expired - Lifetime
- 2003-05-28 AU AU2003241161A patent/AU2003241161C1/en not_active Ceased
- 2003-05-28 US US10/512,094 patent/US7452900B2/en not_active Expired - Fee Related
- 2003-05-28 DK DK09162737.2T patent/DK2112154T3/da active
- 2003-05-28 JP JP2004509687A patent/JP4593270B2/ja not_active Expired - Fee Related
- 2003-05-28 WO PCT/IT2003/000329 patent/WO2003101996A2/en not_active Ceased
- 2003-05-28 MX MXPA04011681A patent/MXPA04011681A/es active IP Right Grant
- 2003-05-28 KR KR1020047016881A patent/KR101000963B1/ko not_active Expired - Fee Related
- 2003-05-28 EP EP09162737.2A patent/EP2112154B1/en not_active Expired - Lifetime
- 2003-05-28 DE DE60328777T patent/DE60328777D1/de not_active Expired - Lifetime
- 2003-05-28 SI SI200332302T patent/SI2112154T1/sl unknown
- 2003-05-28 PT PT91627372T patent/PT2112154E/pt unknown
- 2003-05-28 CA CA2487252A patent/CA2487252C/en not_active Expired - Fee Related
- 2003-05-30 AR ARP030101916A patent/AR040140A1/es not_active Application Discontinuation
- 2003-05-30 PE PE2003000528A patent/PE20040533A1/es not_active Application Discontinuation
-
2007
- 2007-04-10 US US11/783,495 patent/US7498340B2/en not_active Expired - Fee Related
-
2009
- 2009-11-04 CY CY20091101143T patent/CY1109581T1/el unknown
-
2013
- 2013-09-24 CY CY20131100832T patent/CY1114692T1/el unknown
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