公开(公告)号：WO02060904A3

公开(公告)日：2003-02-27

申请号：PCT/US0201853

申请日：2002-01-22

Applicant: SQUIBB BRISTOL MYERS CO ,  LI WEN-SEN ,  THORNTON JOHN E ,  GUO ZHENRONG ,  SWAMINATHAN SHANKAR

Inventor： LI WEN-SEN ,  THORNTON JOHN E ,  GUO ZHENRONG ,  SWAMINATHAN SHANKAR

IPC: C07D417/06 ,  C07D491/044 ,  C07D491/08

CPC classification number: C07D417/06 ,  C07D491/08

Abstract: The present invention relates to a process for the preparation of epothilone analogs by initially forming novel ring-opened epothilones and carrying out a macrolactamization reaction thereon. The subject process is amenable to being carried out in a single reaction vessel without isolation of the intermediate compound and provides at least about a three-fold increase in yield over prior processes for preparing the desired epothilone analogs.

Abstract translation: 本发明涉及通过初始形成新型开环埃坡霉素并在其上进行大环内酯化反应来制备埃坡霉素类似物的方法。 本发明方法适于在单独的反应容器中进行，而不分离中间体化合物，并且与现有的制备所需埃坡霉素类似物的方法相比，产率提高至少约三倍。

公开(公告)号：WO2005058245A3

公开(公告)日：2005-08-04

申请号：PCT/US2004041920

申请日：2004-12-10

Applicant: SQUIBB BRISTOL MYERS CO ,  SWAMINATHAN SHANKAR ,  GAVAI ASHVINIKUMAR V ,  FAN JUNYING ,  PATEL BHARAT P ,  NORRIS DEREK J ,  CORBETT RICHARD MICHAEL ,  ZHENG BIN

Inventor： SWAMINATHAN SHANKAR ,  GAVAI ASHVINIKUMAR V ,  FAN JUNYING ,  PATEL BHARAT P ,  NORRIS DEREK J ,  CORBETT RICHARD MICHAEL ,  ZHENG BIN

IPC: A61K20060101 ,  A61K31/53 ,  A61P35/00 ,  C07D487/04

CPC classification number: C07D487/04

Abstract: The present invention provides a process for preparing compounds of formula (I) ["insert chemical structure here"](I)or a pharmaceutically acceptable salt thereof. The compounds prepared by the process of the invention inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.

Abstract translation: 本发明提供了制备式（I）化合物[“在此插入化学结构”（I））或其药学上可接受的盐的方法。 通过本发明的方法制备的化合物抑制生长因子受体如HER1，HER2和HER4的酪氨酸激酶活性，从而使其可用作治疗癌症和其它疾病的抗增殖剂。

公开(公告)号：EP1694683A4

公开(公告)日：2009-06-24

申请号：EP04814139

申请日：2004-12-10

Applicant: SQUIBB BRISTOL MYERS CO

Inventor： SWAMINATHAN SHANKAR ,  GAVAI ASHVINIKUMAR V ,  FAN JUNYING ,  PATEL BHARAT P ,  NORRIS DEREK J ,  CORBETT RICHARD MICHAEL ,  ZHENG BIN

IPC: C07D487/04 ,  A61K20060101 ,  A61K31/53 ,  A61P35/00

CPC classification number: C07D487/04

公开(公告)号：EP1235792A4

公开(公告)日：2003-06-25

申请号：EP99974268

申请日：1999-07-29

Applicant: SQUIBB BRISTOL MYERS CO

Inventor： MONIOT JEROME L ,  RAMIG KEITH ,  JASS PAUL A ,  DILLON JOHN L JR ,  RACHA SAIBABA ,  SHRIVASTAVA SUSHIL K ,  WINTER WILLIAM J ,  VENIT JOHN J ,  SWAMINATHAN SHANKAR ,  SIMPSON JAMES ,  CHEN CHIEN-KUANG ,  PACK SHAWN K ,  SCHWINDEN MARK D

IPC: C07D513/04 ,  C07B53/00 ,  C07B61/00 ,  C07C229/04 ,  C07C229/22 ,  C07C261/00 ,  C07C319/22 ,  C07C323/59 ,  C07D281/02

CPC classification number: Y02P20/55

Abstract: N-protected-L-homocysteine disulfide of the formula (I) or an activated form thereof is reacted with (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester to give the disulfide intermediate of the formula (II). The disulfide intermediate of formula (II) is reacted to cleave the disulfide bond and the resulting monomer is subjected to an acid catalyzed cyclization reaction to give the N-protected lactam of the formula (III). Removal of the N-protecting group gives [4S-(4 alpha ,7 alpha ,10a beta ]-4-aminooctahydro-5-oxo-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid, methyl ester which along with its salt is useful as an intermediate in the preparation of the dual inhibitor [4S- [4 alpha (R*),7 alpha ,10a beta ]]-octahydro-4-[(2-mercapto-1-oxo-3-phenylpropyl)amino]-5-oxo-7H-pyrido-[2,1-b][1,3]thiazepine-7-carboxylic acid.

公开(公告)号：EP1109928A4

公开(公告)日：2004-10-13

申请号：EP99945367

申请日：1999-08-31

Applicant: SQUIBB BRISTOL MYERS CO

Inventor： PATEL RAMESH N ,  BANERJEE AMIT ,  NANDURI VENKATA B ,  GOLDBERG STEVEN L ,  JOHNSTON ROBERT M ,  TULLY THOMAS P ,  SZARKA LASZLO J ,  SWAMINATHAN SHANKAR ,  VENIT JOHN J ,  MONIOT JEROME L ,  WINTER WILLIAM J ,  ANDERSON NEAL G ,  LUST DAVID A ,  CRISPINO GERARD ,  SRIVASTAVA SUSHIL

IPC: C12N15/09 ,  A61K38/00 ,  C07D513/04 ,  C07K5/062 ,  C07K5/078 ,  C07K14/81 ,  C12N1/20 ,  C12N1/21 ,  C12N9/06 ,  C12N9/10 ,  C12P17/18 ,  C12R1/01 ,  C12R1/38 ,  C12R1/465 ,  C07K5/06 ,  C12N15/52 ,  C12P21/02

CPC classification number: C07K5/06139 ,  A61K38/00 ,  C07K14/8103 ,  C12N9/1096

公开(公告)号：PE20011104A1

公开(公告)日：2001-12-02

申请号：PE2001000256

申请日：2001-03-20

Applicant: SQUIBB BRISTOL MYERS CO

Inventor： GUO ZHENRONG ,  LI WEN SEN ,  THORNTON JOHN E ,  SWAMINATHAN SHANKAR ,  MCCONLOGUE CARY W

IPC: C07D491/044 ,  A61K31/427 ,  A61P9/10 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P27/02 ,  A61P35/00 ,  A61P35/02 ,  C07B61/00 ,  C07D277/30 ,  C07D303/38 ,  C07D417/06 ,  C07D491/04 ,  C07D493/04

Abstract: SE REFIERE A ANALOGOS DE EPOTILONA FORMULA I DONDE Q ES EL GRUPO a, b; M ES O, S, NR6, CR9R10; Z ES R16-N(R17)(R18), R16-P(R17)(R18), R16-Ar(R17)(R18); R1-R5 Y R11-R15 SON H, ALQUILO, ARILO, HETEROCICLO, DONDE R1 Y R2 SON ALQUILO Y JUNTOS FORMAN UN CICLOALQUILO; R6 ES H, ALQUILO, ARILO, CICLOALQUILO, ENTRE OTROS; R8 ES H, ALQUILO, R11C=O, R12OC=O, R13SO2; R9 Y R10 SON H, HALO, ALQUILO, ARILO, HETEROCICLO ENTRE OTROS; R16, R17 Y R18 SON ALQUILO, ARILO, ARALQUILO. SE REFIERE TAMBIEN A UN PROCESO PARA LA PREPARACION DE ANALOGOS DE EPOTILONA TAL COMO [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-DIHIDROXI -8,8,10,12,16-PENTAMETIL-3-[1-METIL-2-(2-METIL-4-TIAZOLIL)ETENIL]-4-AZA-17-OXABICICLO [14.1.0]HEPTADECAN-5,9-DIONA Y COMPUESTOS INTERMEDIOS MEDIANTE LA FORMACION DE NUEVAS EPOTILONAS DE ANILLO ABIERTO Y LLEVAR A CABO UNA REACCION DE MACROLACTAMIZACION CON UN AGENTE DE ACOPLAMIENTO TAL COMO 1-(3-DIMETILAMINOPROPIL)-3-ETILCARBODIIMIDA, ENTRE OTROS. LOS COMPUESTOS DE FORMULA I SON UTILES PARA EL TRATAMIENTO DE CANCER, TUMORES

公开(公告)号：HK1050680A1

公开(公告)日：2003-07-04

申请号：HK03102703

申请日：2003-04-14

Applicant: SQUIBB BRISTOL MYERS CO

Inventor： LI WEN SEN ,  THORNTON JOHN E ,  GUO ZHENRONG ,  SWAMINATHAN SHANKAR ,  MCCONLOGUE GARY W

IPC: C07D491/044 ,  A61K31/427 ,  A61P9/10 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P27/02 ,  A61P35/00 ,  A61P35/02 ,  C07B61/00 ,  C07D20060101 ,  C07D303/38 ,  C07D417/06 ,  C07D491/04

Abstract: The present invention relates to a process for the preparation of epothilone analogs by initially forming novel ring-opended epothilones and carrying out a macrolactamization reaction thereon. The subject process is amenable to being carried out in a single reaction vessel without isolation of the intermediate compound and provides at least about a threefold increase in yield over prior processes for preparing the desired epothilone analogs.

公开(公告)号：AU2002240014A1

公开(公告)日：2002-08-12

申请号：AU2002240014

申请日：2002-01-22

Applicant: SQUIBB BRISTOL MYERS CO

Inventor： SWAMINATHAN SHANKAR ,  GUO ZHENRONG ,  LI WEN-SEN ,  THORNTON JOHN E

IPC: C07D417/06 ,  C07D491/044 ,  C07D491/08

Abstract: The present invention relates to a process for the preparation of epothilone analogs by initially forming novel ring-opened epothilones and carrying out a macrolactamization reaction thereon. The subject process is amenable to being carried out in a single reaction vessel without isolation of the intermediate compound and provides at least about a three-fold increase in yield over prior processes for preparing the desired epothilone analogs.

公开(公告)号：PE11042001A1

公开(公告)日：2001-12-02

申请号：PE0002562001

申请日：2001-03-20

Applicant: SQUIBB BRISTOL MYERS CO

Inventor： GUO ZHENRONG ,  LI WEN SEN ,  THORNTON JOHN E ,  SWAMINATHAN SHANKAR ,  MCCONLOGUE CARY W

IPC: C07D491/044 ,  A61K31/427 ,  A61P9/10 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P27/02 ,  A61P35/00 ,  A61P35/02 ,  C07B61/00 ,  C07D277/30 ,  C07D303/38 ,  C07D417/06 ,  C07D491/04 ,  C07D493/04

CPC classification number: C07D303/38 ,  C07D417/06 ,  C07D491/04

Abstract: SE REFIERE A ANALOGOS DE EPOTILONA FORMULA I DONDE Q ES EL GRUPO a, b; M ES O, S, NR6, CR9R10; Z ES R16-N(R17)(R18), R16-P(R17)(R18), R16-Ar(R17)(R18); R1-R5 Y R11-R15 SON H, ALQUILO, ARILO, HETEROCICLO, DONDE R1 Y R2 SON ALQUILO Y JUNTOS FORMAN UN CICLOALQUILO; R6 ES H, ALQUILO, ARILO, CICLOALQUILO, ENTRE OTROS; R8 ES H, ALQUILO, R11C=O, R12OC=O, R13SO2; R9 Y R10 SON H, HALO, ALQUILO, ARILO, HETEROCICLO ENTRE OTROS; R16, R17 Y R18 SON ALQUILO, ARILO, ARALQUILO. SE REFIERE TAMBIEN A UN PROCESO PARA LA PREPARACION DE ANALOGOS DE EPOTILONA TAL COMO [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-DIHIDROXI -8,8,10,12,16-PENTAMETIL-3-[1-METIL-2-(2-METIL-4-TIAZOLIL)ETENIL]-4-AZA-17-OXABICICLO [14.1.0]HEPTADECAN-5,9-DIONA Y COMPUESTOS INTERMEDIOS MEDIANTE LA FORMACION DE NUEVAS EPOTILONAS DE ANILLO ABIERTO Y LLEVAR A CABO UNA REACCION DE MACROLACTAMIZACION CON UN AGENTE DE ACOPLAMIENTO TAL COMO 1-(3-DIMETILAMINOPROPIL)-3-ETILCARBODIIMIDA, ENTRE OTROS. LOS COMPUESTOS DE FORMULA I SON UTILES PARA EL TRATAMIENTO DE CANCER, TUMORES

公开(公告)号：AT516280T

公开(公告)日：2011-07-15

申请号：AT01918544

申请日：2001-03-12

Applicant: SQUIBB BRISTOL MYERS CO

Inventor： LI WEN ,  THORNTON JOHN ,  GUO ZHENRONG ,  SWAMINATHAN SHANKAR

IPC: C07D303/38 ,  C07D491/044 ,  A61K31/427 ,  A61P9/10 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P27/02 ,  A61P35/00 ,  A61P35/02 ,  C07B61/00 ,  C07D417/06 ,  C07D491/04

Abstract: The present invention relates to a process for the preparation of epothilone analogs by initially forming novel ring-opended epothilones and carrying out a macrolactamization reaction thereon. The subject process is amenable to being carried out in a single reaction vessel without isolation of the intermediate compound and provides at least about a threefold increase in yield over prior processes for preparing the desired epothilone analogs.