ES2436296T3 - Trans-9,10-dehidroepotilona C y trans-9,10-dehidroepotilona D, sus análogos y procedimientos de fabricación de las mismas - Google Patents

Trans-9,10-dehidroepotilona C y trans-9,10-dehidroepotilona D, sus análogos y procedimientos de fabricación de las mismas Download PDF

Info

Publication number: ES2436296T3
Authority: ES; Spain
Prior art keywords: compound; dehydroepotilone; alkyl; compounds; trans
Prior art date: 2002-11-07
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 - Lifetime

Application number

ES09012671T

Other languages

English (en)

Spanish (es)

Inventor

Yong Li

Kurt Sundermann

Li Tang

David Myles

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Kosan Biosciences Inc

Original Assignee

Kosan Biosciences Inc

Priority date (The priority date 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 date listed.)

2002-11-07

Filing date

2003-11-07

Publication date

2013-12-30

2003-11-07 Application filed by Kosan Biosciences Inc filed Critical Kosan Biosciences Inc

2013-12-30 Application granted granted Critical

2013-12-30 Publication of ES2436296T3 publication Critical patent/ES2436296T3/es

2023-11-07 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

238000004519 manufacturing process Methods 0.000 title abstract description 10
150000001875 compounds Chemical class 0.000 claims description 154
239000000203 mixture Substances 0.000 claims description 78
-1 = C1-4 N-alkoxy Chemical group 0.000 claims description 76
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 22
206010028980 Neoplasm Diseases 0.000 claims description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
201000011510 cancer Diseases 0.000 claims description 17
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
238000011282 treatment Methods 0.000 claims description 16
201000010099 disease Diseases 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
125000001475 halogen functional group Chemical group 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 11
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 10
241001465754 Metazoa Species 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
230000001413 cellular effect Effects 0.000 claims description 8
230000003463 hyperproliferative effect Effects 0.000 claims description 8
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 7
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
201000001320 Atherosclerosis Diseases 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 5
206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
208000037803 restenosis Diseases 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
206010009944 Colon cancer Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
125000004945 acylaminoalkyl group Chemical group 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
125000004663 dialkyl amino group Chemical group 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
201000006417 multiple sclerosis Diseases 0.000 claims description 3
208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
125000004043 oxo group Chemical group O=* 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000000335 thiazolyl group Chemical group 0.000 claims description 3
125000005309 thioalkoxy group Chemical group 0.000 claims description 3
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
239000000825 pharmaceutical preparation Substances 0.000 claims description 2
229940127557 pharmaceutical product Drugs 0.000 claims description 2
239000013543 active substance Substances 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
239000000243 solution Substances 0.000 description 68
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
238000000034 method Methods 0.000 description 44
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 40
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 37
239000000047 product Substances 0.000 description 37
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
238000006243 chemical reaction Methods 0.000 description 30
239000000543 intermediate Substances 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
210000004027 cell Anatomy 0.000 description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
229930013356 epothilone Natural products 0.000 description 23
238000010898 silica gel chromatography Methods 0.000 description 22
238000003786 synthesis reaction Methods 0.000 description 22
XOZIUKBZLSUILX-SDMHVBBESA-N Epothilone D Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C(/C)=C/C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C XOZIUKBZLSUILX-SDMHVBBESA-N 0.000 description 21
230000015572 biosynthetic process Effects 0.000 description 21
239000012267 brine Substances 0.000 description 21
XOZIUKBZLSUILX-UHFFFAOYSA-N desoxyepothilone B Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC(C)=CCC1C(C)=CC1=CSC(C)=N1 XOZIUKBZLSUILX-UHFFFAOYSA-N 0.000 description 21
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
230000000694 effects Effects 0.000 description 20
229910052943 magnesium sulfate Inorganic materials 0.000 description 20
235000019341 magnesium sulphate Nutrition 0.000 description 20
XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 description 19
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
235000017557 sodium bicarbonate Nutrition 0.000 description 18
229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 18
HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
239000002585 base Substances 0.000 description 15
150000003883 epothilone derivatives Chemical class 0.000 description 15
230000009467 reduction Effects 0.000 description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
239000007787 solid Substances 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
230000005764 inhibitory process Effects 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
102000004243 Tubulin Human genes 0.000 description 10
108090000704 Tubulin Proteins 0.000 description 10
239000000284 extract Substances 0.000 description 10
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
229920000858 Cyclodextrin Polymers 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
235000019270 ammonium chloride Nutrition 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
239000003814 drug Substances 0.000 description 9
VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
239000008389 polyethoxylated castor oil Substances 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
230000008030 elimination Effects 0.000 description 8
238000003379 elimination reaction Methods 0.000 description 8
150000001261 hydroxy acids Chemical class 0.000 description 8
108090000623 proteins and genes Proteins 0.000 description 8
125000000217 alkyl group Chemical group 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
238000010511 deprotection reaction Methods 0.000 description 7
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
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150000004714 phosphonium salts Chemical class 0.000 description 7
230000035755 proliferation Effects 0.000 description 7
102000004169 proteins and genes Human genes 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
239000006228 supernatant Substances 0.000 description 7
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 7
GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 6
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UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 6
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TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 6
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

ES09012671T 2002-11-07 2003-11-07 Trans-9,10-dehidroepotilona C y trans-9,10-dehidroepotilona D, sus análogos y procedimientos de fabricación de las mismas Expired - Lifetime ES2436296T3 (es)

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US425352P		2002-11-07
US47374303P	2003-05-27	2003-05-27
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ES03768730T Expired - Lifetime ES2336911T3 (es)	2002-11-07	2003-11-07	Trans-9,10-dehidroepotilonas c y d, sus analogos y procedimientos de preparacion.

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US (2)	US20040152708A1 (2)
EP (3)	EP1562941B1 (2)
JP (3)	JP4641941B2 (2)
KR (2)	KR100966667B1 (2)
AT (1)	ATE452888T1 (2)
AU (1)	AU2003291337B2 (2)
CA (1)	CA2505368C (2)
CY (1)	CY1110295T1 (2)
DE (1)	DE60330703D1 (2)
DK (1)	DK1562941T3 (2)
ES (2)	ES2436296T3 (2)
PT (1)	PT1562941E (2)
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2003
- 2003-11-07 EP EP03768730A patent/EP1562941B1/en not_active Expired - Lifetime
- 2003-11-07 ES ES09012671T patent/ES2436296T3/es not_active Expired - Lifetime
- 2003-11-07 KR KR1020057008039A patent/KR100966667B1/ko not_active Expired - Fee Related
- 2003-11-07 EP EP09012671.5A patent/EP2135867B1/en not_active Expired - Lifetime
- 2003-11-07 DK DK03768730.8T patent/DK1562941T3/da active
- 2003-11-07 EP EP09012860A patent/EP2135868A1/en not_active Withdrawn
- 2003-11-07 ES ES03768730T patent/ES2336911T3/es not_active Expired - Lifetime
- 2003-11-07 PT PT03768730T patent/PT1562941E/pt unknown
- 2003-11-07 AT AT03768730T patent/ATE452888T1/de active
- 2003-11-07 US US10/703,404 patent/US20040152708A1/en not_active Abandoned
- 2003-11-07 AU AU2003291337A patent/AU2003291337B2/en not_active Ceased
- 2003-11-07 WO PCT/US2003/035411 patent/WO2004043954A2/en not_active Ceased
- 2003-11-07 KR KR1020107000780A patent/KR100996996B1/ko not_active Expired - Fee Related
- 2003-11-07 DE DE60330703T patent/DE60330703D1/de not_active Expired - Lifetime
- 2003-11-07 CA CA2505368A patent/CA2505368C/en not_active Expired - Fee Related
- 2003-11-07 SI SI200331732T patent/SI1562941T1/sl unknown
- 2003-11-07 JP JP2005507102A patent/JP4641941B2/ja not_active Expired - Fee Related
2008
- 2008-07-11 US US12/172,174 patent/US20090186927A1/en not_active Abandoned
2010
- 2010-03-19 CY CY20101100250T patent/CY1110295T1/el unknown
- 2010-10-08 JP JP2010228356A patent/JP5679757B2/ja not_active Expired - Fee Related
2013
- 2013-07-16 JP JP2013147528A patent/JP2013213054A/ja active Pending

Also Published As

Publication number	Publication date
JP4641941B2 (ja)	2011-03-02
ATE452888T1 (de)	2010-01-15
ES2336911T3 (es)	2010-04-19
WO2004043954A3 (en)	2004-11-18
KR100966667B1 (ko)	2010-06-29
KR100996996B1 (ko)	2010-11-25
JP2011006480A (ja)	2011-01-13
EP2135867A1 (en)	2009-12-23
JP2013213054A (ja)	2013-10-17
AU2003291337B2 (en)	2010-09-09
EP1562941A2 (en)	2005-08-17
JP5679757B2 (ja)	2015-03-04
US20040152708A1 (en)	2004-08-05
KR20050084959A (ko)	2005-08-29
KR20100018075A (ko)	2010-02-16
US20090186927A1 (en)	2009-07-23
SI1562941T1 (sl)	2010-05-31
EP2135867B1 (en)	2013-09-25
EP2135868A1 (en)	2009-12-23
PT1562941E (pt)	2010-01-25
CA2505368A1 (en)	2004-05-27
WO2004043954A2 (en)	2004-05-27
CA2505368C (en)	2011-09-20
DK1562941T3 (da)	2010-04-19
DE60330703D1 (de)	2010-02-04
AU2003291337A1 (en)	2004-06-03
EP1562941B1 (en)	2009-12-23
JP2006510743A (ja)	2006-03-30
CY1110295T1 (el)	2015-01-14

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