RU2243223C2 - С-4 карбонатсодержащие таксаны - Google Patents
С-4 карбонатсодержащие таксаны Download PDFInfo
- Publication number
- RU2243223C2 RU2243223C2 RU2002123641/04A RU2002123641A RU2243223C2 RU 2243223 C2 RU2243223 C2 RU 2243223C2 RU 2002123641/04 A RU2002123641/04 A RU 2002123641/04A RU 2002123641 A RU2002123641 A RU 2002123641A RU 2243223 C2 RU2243223 C2 RU 2243223C2
- Authority
- RU
- Russia
- Prior art keywords
- compound
- tert
- paclitaxel
- butyl
- solution
- Prior art date
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- 229940123237 Taxane Drugs 0.000 title abstract description 27
- 230000000259 anti-tumor effect Effects 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 3
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 52
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 230000004614 tumor growth Effects 0.000 claims description 3
- 229940125890 compound Ia Drugs 0.000 claims description 2
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- 230000000694 effects Effects 0.000 abstract description 17
- 238000011282 treatment Methods 0.000 abstract description 16
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 abstract description 12
- 241001465754 Metazoa Species 0.000 abstract description 11
- 239000002246 antineoplastic agent Substances 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 4
- 229930014626 natural product Natural products 0.000 abstract description 2
- 230000007721 medicinal effect Effects 0.000 abstract 1
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
- -1 docetaxel Chemical class 0.000 description 44
- 239000000243 solution Substances 0.000 description 43
- 206010028980 Neoplasm Diseases 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical class 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 33
- 229960001592 paclitaxel Drugs 0.000 description 31
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 29
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- 239000011541 reaction mixture Substances 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 22
- 239000012267 brine Substances 0.000 description 21
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
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- 229930190007 Baccatin Natural products 0.000 description 16
- 239000000047 product Substances 0.000 description 16
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- 238000003786 synthesis reaction Methods 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 238000010828 elution Methods 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 9
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- 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 description 8
- 201000011510 cancer Diseases 0.000 description 8
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- 125000006239 protecting group Chemical group 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
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- 125000003118 aryl group Chemical group 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
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- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5beta,20-epoxy-1,7beta,13alpha-trihydroxy-9-oxotax-11-ene-2alpha,4alpha,10beta-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)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)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 description 5
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
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- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
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- XPJWTYCCTBCCOG-KBPBESRZSA-N tert-butyl (2r,3s)-2-tert-butyl-4-oxo-3-triethylsilyloxyazetidine-1-carboxylate Chemical compound CC[Si](CC)(CC)O[C@H]1[C@@H](C(C)(C)C)N(C(=O)OC(C)(C)C)C1=O XPJWTYCCTBCCOG-KBPBESRZSA-N 0.000 description 1
- DHHKPEUQJIEKOA-UHFFFAOYSA-N tert-butyl 2-[6-(nitromethyl)-6-bicyclo[3.2.0]hept-3-enyl]acetate Chemical compound C1C=CC2C(CC(=O)OC(C)(C)C)(C[N+]([O-])=O)CC21 DHHKPEUQJIEKOA-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical class CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- NTJBWZHVSJNKAD-UHFFFAOYSA-N triethylazanium;fluoride Chemical compound [F-].CC[NH+](CC)CC NTJBWZHVSJNKAD-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Carbon And Carbon Compounds (AREA)
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|---|---|---|---|
| US17996500P | 2000-02-03 | 2000-02-03 | |
| US60/179,965 | 2000-02-03 |
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| RU2002123641A RU2002123641A (ru) | 2004-01-10 |
| RU2243223C2 true RU2243223C2 (ru) | 2004-12-27 |
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| RU2002123641/04A RU2243223C2 (ru) | 2000-02-03 | 2000-11-16 | С-4 карбонатсодержащие таксаны |
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| EP (1) | EP1251846B1 (enExample) |
| JP (1) | JP2003523971A (enExample) |
| AT (1) | ATE273005T1 (enExample) |
| AU (1) | AU778284B2 (enExample) |
| CA (1) | CA2399116A1 (enExample) |
| CZ (1) | CZ20022956A3 (enExample) |
| DE (1) | DE60012988T2 (enExample) |
| DK (1) | DK1251846T3 (enExample) |
| ES (1) | ES2226954T3 (enExample) |
| HK (1) | HK1047891B (enExample) |
| MY (1) | MY129310A (enExample) |
| NZ (1) | NZ521136A (enExample) |
| PE (1) | PE20020747A1 (enExample) |
| PT (1) | PT1251846E (enExample) |
| RU (1) | RU2243223C2 (enExample) |
| TR (1) | TR200402454T4 (enExample) |
| TW (2) | TWI245042B (enExample) |
| WO (1) | WO2001056565A1 (enExample) |
| ZA (1) | ZA200207037B (enExample) |
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| US6916942B2 (en) * | 2000-02-03 | 2005-07-12 | Bristol-Myers Squibb Company | Process for the preparation of C-4 carbonate taxanes |
| US6750246B1 (en) | 2000-02-03 | 2004-06-15 | Bristol-Myers Squibb Company | C-4 carbonate taxanes |
| UY27185A1 (es) * | 2001-02-28 | 2002-09-30 | Bristol Myers Squibb Co | Dosificación metronómica de taxanos |
| EP1623706A3 (en) * | 2001-02-28 | 2006-02-22 | Bristol-Myers Squibb Company | Metronomic dosing of taxanes for inhibiting tumor growth |
| US7063977B2 (en) * | 2001-08-21 | 2006-06-20 | Bristol-Myers Squibb Company | Enzymatic resolution of t-butyl taxane derivatives |
| CA2470826A1 (en) * | 2001-12-20 | 2003-07-03 | Bristol-Myers Squibb Company | Pharmaceutical compositions of orally active taxane derivatives having enhanced bioavailability |
| US20070105944A1 (en) * | 2002-10-25 | 2007-05-10 | Comezoglu S N | Taxane metabolites |
| US7371759B2 (en) * | 2003-09-25 | 2008-05-13 | Bristol-Myers Squibb Company | HMG-CoA reductase inhibitors and method |
| TW200533339A (en) * | 2004-03-16 | 2005-10-16 | Bristol Myers Squibb Co | Therapeutic synergy of anti-cancer compounds |
| US7459562B2 (en) * | 2004-04-23 | 2008-12-02 | Bristol-Myers Squibb Company | Monocyclic heterocycles as kinase inhibitors |
| TW200538453A (en) * | 2004-04-26 | 2005-12-01 | Bristol Myers Squibb Co | Bicyclic heterocycles as kinase inhibitors |
| US7432373B2 (en) * | 2004-06-28 | 2008-10-07 | Bristol-Meyers Squibb Company | Processes and intermediates useful for preparing fused heterocyclic kinase inhibitors |
| US20050288290A1 (en) | 2004-06-28 | 2005-12-29 | Borzilleri Robert M | Fused heterocyclic kinase inhibitors |
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- 2000-11-16 EP EP00980427A patent/EP1251846B1/en not_active Expired - Lifetime
- 2000-11-16 RU RU2002123641/04A patent/RU2243223C2/ru not_active IP Right Cessation
- 2000-11-16 JP JP2001556256A patent/JP2003523971A/ja active Pending
- 2000-11-16 ES ES00980427T patent/ES2226954T3/es not_active Expired - Lifetime
- 2000-11-16 CA CA002399116A patent/CA2399116A1/en not_active Abandoned
- 2000-11-16 CZ CZ20022956A patent/CZ20022956A3/cs unknown
- 2000-11-16 DE DE60012988T patent/DE60012988T2/de not_active Expired - Lifetime
- 2000-11-16 WO PCT/US2000/031484 patent/WO2001056565A1/en not_active Ceased
- 2000-11-16 PT PT00980427T patent/PT1251846E/pt unknown
- 2000-11-16 AU AU17692/01A patent/AU778284B2/en not_active Ceased
- 2000-11-16 HK HK03100017.6A patent/HK1047891B/en not_active IP Right Cessation
- 2000-11-16 AT AT00980427T patent/ATE273005T1/de active
- 2000-11-16 TR TR2004/02454T patent/TR200402454T4/xx unknown
- 2000-11-16 DK DK00980427T patent/DK1251846T3/da active
- 2000-11-16 NZ NZ521136A patent/NZ521136A/en unknown
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2001
- 2001-01-29 MY MYPI20010372A patent/MY129310A/en unknown
- 2001-01-29 TW TW094114392A patent/TWI245042B/zh not_active IP Right Cessation
- 2001-01-29 TW TW090101690A patent/TWI245041B/zh not_active IP Right Cessation
- 2001-02-02 PE PE2001000117A patent/PE20020747A1/es not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| PT1251846E (pt) | 2004-11-30 |
| JP2003523971A (ja) | 2003-08-12 |
| CA2399116A1 (en) | 2001-08-09 |
| DK1251846T3 (da) | 2004-11-29 |
| RU2002123641A (ru) | 2004-01-10 |
| DE60012988D1 (en) | 2004-09-16 |
| AU1769201A (en) | 2001-08-14 |
| HK1047891A1 (en) | 2003-03-14 |
| AU778284B2 (en) | 2004-11-25 |
| HK1047891B (en) | 2005-01-28 |
| US6750246B1 (en) | 2004-06-15 |
| ES2226954T3 (es) | 2005-04-01 |
| TWI245041B (en) | 2005-12-11 |
| TW200526613A (en) | 2005-08-16 |
| TWI245042B (en) | 2005-12-11 |
| ZA200207037B (en) | 2003-12-02 |
| MY129310A (en) | 2007-03-30 |
| EP1251846B1 (en) | 2004-08-11 |
| TR200402454T4 (tr) | 2004-12-21 |
| EP1251846A4 (en) | 2003-03-12 |
| ATE273005T1 (de) | 2004-08-15 |
| DE60012988T2 (de) | 2005-08-25 |
| EP1251846A1 (en) | 2002-10-30 |
| CZ20022956A3 (cs) | 2003-02-12 |
| PE20020747A1 (es) | 2002-08-17 |
| WO2001056565A1 (en) | 2001-08-09 |
| NZ521136A (en) | 2004-05-28 |
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| Date | Code | Title | Description |
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| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20071117 |