AU2003291337B2 - Trans-9,10-dehydroepothilone C and D, analogs thereof and methos of making the same - Google Patents

Trans-9,10-dehydroepothilone C and D, analogs thereof and methos of making the same Download PDF

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Publication number: AU2003291337B2
Authority: AU; Australia
Prior art keywords: compound; dehydroepothilone; epothilone; oxo; solution
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.): Ceased

Application number

AU2003291337A

Other languages

English (en)

Other versions

AU2003291337A1 (en

Inventor

Yong Li

David Myles

Kurt Sundermann

Li Tang

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

2010-09-09

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

2004-06-03 Publication of AU2003291337A1 publication Critical patent/AU2003291337A1/en

2010-09-09 Application granted granted Critical

2010-09-09 Publication of AU2003291337B2 publication Critical patent/AU2003291337B2/en

2023-11-07 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

238000004519 manufacturing process Methods 0.000 claims abstract description 10
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238000000034 method Methods 0.000 claims description 57
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206010028980 Neoplasm Diseases 0.000 claims description 26
201000011510 cancer Diseases 0.000 claims description 20
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
238000011282 treatment Methods 0.000 claims description 19
201000010099 disease Diseases 0.000 claims description 18
230000001413 cellular effect Effects 0.000 claims description 13
241001465754 Metazoa Species 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 11
230000003463 hyperproliferative effect Effects 0.000 claims description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
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239000003814 drug Substances 0.000 claims description 8
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
239000012991 xanthate Substances 0.000 claims description 7
201000001320 Atherosclerosis Diseases 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 6
206010006187 Breast cancer Diseases 0.000 claims description 5
208000026310 Breast neoplasm Diseases 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical compound CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 claims description 5
206010009944 Colon cancer Diseases 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
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208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
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GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 claims description 3
125000004945 acylaminoalkyl group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
125000005277 alkyl imino group Chemical group 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
201000006417 multiple sclerosis Diseases 0.000 claims description 3
125000004043 oxo group Chemical group O=* 0.000 claims description 3
238000000197 pyrolysis Methods 0.000 claims description 3
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125000005309 thioalkoxy group Chemical group 0.000 claims description 3
239000013543 active substance Substances 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
239000000243 solution Substances 0.000 description 116
239000000047 product Substances 0.000 description 100
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
238000006243 chemical reaction Methods 0.000 description 58
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 58
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
239000012267 brine Substances 0.000 description 37
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
239000000543 intermediate Substances 0.000 description 36
239000000741 silica gel Substances 0.000 description 33
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230000015572 biosynthetic process Effects 0.000 description 30
239000000284 extract Substances 0.000 description 30
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QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
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238000004587 chromatography analysis Methods 0.000 description 27
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 27
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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 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
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 24
238000003786 synthesis reaction Methods 0.000 description 24
210000004027 cell Anatomy 0.000 description 23
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 23
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
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 21
238000004809 thin layer chromatography Methods 0.000 description 21
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 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
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239000002585 base Substances 0.000 description 17
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239000007858 starting material Substances 0.000 description 17
VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 description 16
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
230000008030 elimination Effects 0.000 description 15
238000003379 elimination reaction Methods 0.000 description 15
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
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OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 12
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 12
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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 10
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QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 6
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IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 5
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- C07D405/00—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
- 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
- C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
- C—CHEMISTRY; METALLURGY
- 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
- C07D417/02—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 containing two hetero rings
- C07D417/06—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 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

AU2003291337A 2002-11-07 2003-11-07 Trans-9,10-dehydroepothilone C and D, analogs thereof and methos of making the same Ceased AU2003291337B2 (en)

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US42535202P	2002-11-07	2002-11-07
US60/425,352		2002-11-07
US47374303P	2003-05-27	2003-05-27
US60/473,743		2003-05-27
PCT/US2003/035411 WO2004043954A2 (en)	2002-11-07	2003-11-07	Trans-9,10-dehydroepothilone c and d, analogs thereof and methos of making the same

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US (2)	US20040152708A1 (2)
EP (3)	EP2135867B1 (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)	ES2336911T3 (2)
PT (1)	PT1562941E (2)
SI (1)	SI1562941T1 (2)
WO (1)	WO2004043954A2 (2)

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US7649006B2 (en)	2002-08-23	2010-01-19	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
DE60330407D1 (de)	2002-08-23	2010-01-14	Sloan Kettering Inst Cancer	Synthese von Epothilonen, Zwischenprodukte davon, Analoga und ihre Verwendung
US6921769B2 (en)	2002-08-23	2005-07-26	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
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BRPI0408891A (pt) *	2003-03-28	2006-04-11	Kosan Biosciences Inc	dispositivos, métodos, e composições para prevenir restenose
EP1670487A4 (en) *	2003-10-09	2008-05-21	Kosan Biosciences Inc	THERAPEUTIC FORMULATIONS
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US20130072439A1 (en)	2009-09-22	2013-03-21	Huw M. Nash	Peptidomimetic macrocycles
KR20170058446A (ko)	2010-08-13	2017-05-26	에일러론 테라퓨틱스 인코포레이티드	펩티도미메틱 거대고리
AR088392A1 (es)	2011-10-18	2014-05-28	Aileron Therapeutics Inc	Macrociclos peptidomimeticos
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Publication number	Publication date
EP1562941B1 (en)	2009-12-23
JP5679757B2 (ja)	2015-03-04
CY1110295T1 (el)	2015-01-14
WO2004043954A3 (en)	2004-11-18
JP2013213054A (ja)	2013-10-17
ES2336911T3 (es)	2010-04-19
DE60330703D1 (de)	2010-02-04
EP2135868A1 (en)	2009-12-23
KR100966667B1 (ko)	2010-06-29
EP2135867B1 (en)	2013-09-25
DK1562941T3 (da)	2010-04-19
KR100996996B1 (ko)	2010-11-25
JP4641941B2 (ja)	2011-03-02
KR20050084959A (ko)	2005-08-29
KR20100018075A (ko)	2010-02-16
JP2011006480A (ja)	2011-01-13
ES2436296T3 (es)	2013-12-30
ATE452888T1 (de)	2010-01-15
PT1562941E (pt)	2010-01-25
JP2006510743A (ja)	2006-03-30
CA2505368A1 (en)	2004-05-27
SI1562941T1 (sl)	2010-05-31
EP1562941A2 (en)	2005-08-17
WO2004043954A2 (en)	2004-05-27
AU2003291337A1 (en)	2004-06-03
US20040152708A1 (en)	2004-08-05
CA2505368C (en)	2011-09-20
US20090186927A1 (en)	2009-07-23
EP2135867A1 (en)	2009-12-23

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