公开(公告)号：WO9411377A3

公开(公告)日：1994-08-04

申请号：PCT/US9310987

申请日：1993-11-10

Applicant: GLAXO INC ,  BESTERMAN JEFFREY MARK ,  EVANS MICHAEL GLENN ,  LACKEY KAREN ELIZABETH ,  LUZZIO MICHAEL JOSEPH ,  PEEL MICHAEL ROBERT ,  STERNBACH DANIEL DAVID

Inventor： BESTERMAN JEFFREY MARK ,  EVANS MICHAEL GLENN ,  LACKEY KAREN ELIZABETH ,  LUZZIO MICHAEL JOSEPH ,  PEEL MICHAEL ROBERT ,  STERNBACH DANIEL DAVID

IPC: A61K31/47 ,  A61K31/675 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07F9/6561

CPC classification number: C07D317/66 ,  C07D319/18

Abstract: The present invention relates to water soluble, camptothecin derivatives of formula (I), wherein A represents a moiety of formula (IIA), (IIB) or (IIC), X is selected from the group consisting of alkyl, aryl, (CH2)mOR1, (CH2)mSR1 and (CH¿2?)mNR?1R2¿ wherein m is an integer of 0 to 6, and R?1 and R2¿ are hydrogen, lower alkyl, aryl or together with the nitrogen form a 5-7 membered ring; q is an integer of 0 to 2; n represents the integer 1 or 2; p is an integer of 1 to 6; Y and W are selected from the group consisting of alkyl, aryl, alkoxy, aryloxy and amino, Q is oxygen or sulfur; P is phosphorus; J represents the atoms necessary to complete a 5 or 6 membered aromatic ring; and the pharmaceutically acceptable salts thereof; their use as topoisomerase inhibitors, their preparation; and their use in the treatment of cancer.

公开(公告)号：ZA9308385B

公开(公告)日：1994-08-09

申请号：ZA9308385

申请日：1993-11-10

Applicant: GLAXO INC

Inventor： LACKEY KAREN ,  LUZZIO MICHAEL JOSEPH ,  EVANS MICHAEL GLENN ,  BESTERMAN JEFFREY MARK ,  STERNBACH DANIEL DAVID ,  PEEL MICHAEL ROBERT

IPC: A61K20060101 ,  C07D20060101 ,  C07D ,  A61K

公开(公告)号：CA2161681A1

公开(公告)日：1994-11-10

申请号：CA2161681

申请日：1994-04-28

Applicant: GLAXO INC

Inventor： BESTERMAN JEFFREY MARK ,  EVANS MICHAEL GLENN ,  LUZZIO MICHAEL JOSEPH ,  MYERS PETER LESLIE

IPC: A61K20060101 ,  A61K31/47 ,  A61P35/00 ,  C07D20060101 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  A61K31/435 ,  C07D405/12 ,  C07D407/12

Abstract: The present invention relates to water soluble, camptothecin derivatives of formula (I), wherein: n represents the integer 1 or 2; and i) R1 represents: hydrogen, lower alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, amino lower allcyl, lower alkylamino lower alkyl, amino lower alkyl, lower alkoxy lower alkyl or (CH2)tAr wherein: t is 0 to 5 and Ar represents phenyl, furyl, pyridyl, N-methylpyrrolyl, imidazolyl; or phenyl, furyl, pyridyl, N-methylpyrrolyl, imidazol, with one or more substituents independently selected from hydroxy, methoxy, halogen, and amino; and R2 represents: diphenylmethyl or (CH2)tAr; or ii) R1 and R2 taken together with the linking nitrogen represent N-tetrahydroquinolyl or N-tetrahydroisoquinolyl; and the pharmaceutically acceptable salts and solvates thereof, their use in the treatment of tumors and methods of their preparation.

公开(公告)号：CA2148819A1

公开(公告)日：1994-05-26

申请号：CA2148819

申请日：1993-11-10

Applicant: GLAXO INC

Inventor： BESTERMAN JEFFREY MARK ,  EVANS MICHAEL GLENN ,  LACKEY KAREN ELIZABETH ,  LUZZIO MICHAEL JOSEPH ,  PEEL MICHAEL ROBERT ,  STERNBACH DANIEL DAVID

IPC: A61K31/47 ,  A61K31/675 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07F9/6561 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  A61K31/395

Abstract: 2148819 9411377 PCTABScor01 The present invention relates to water soluble, camptothecin derivatives of formula (I), wherein A represents a moiety of formula (IIA), (IIB) or (IIC), X is selected from the group consisting of alkyl, aryl, (CH2)mOR1, (CH2)mSR1 and (CH2)mNR1R2 wherein m is an integer of 0 to 6, and R1 and R2 are hydrogen, lower alkyl, aryl or together with the nitrogen form a 5-7 membered ring; q is an integer of 0 to 2; n represents the integer 1 or 2; p is an integer of 1 to 6; Y and W are selected from the group consisting of alkyl, aryl, alkoxy, aryloxy and amino, Q is oxygen or sulfur; P is phosphorus; J represents the atoms necessary to complete a 5 or 6 membered aromatic ring; and the pharmaceutically acceptable salts thereof; their use as topoisomerase inhibitors, their preparation; and their use in the treatment of cancer.

公开(公告)号：AP9300587A0

公开(公告)日：1995-05-05

申请号：AP9300587

申请日：1993-11-05

Applicant: GLAXO INC

Inventor： LACKEY KAREN ELIZABETH ,  LUZZIO MICHAEL JOSEPH ,  EVANS MICHAEL GLENN ,  BESTERMAN JEFFREY M ,  STERNBACH DANIEL DAVID ,  PEEL MICHAEL ROBERT

IPC: A61K31/47 ,  A61K31/675 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07F9/6561

Abstract: The present invention relates to water soluble, camptothecin derivatives of formular (1).WHerein a represents a moiety of the formula (11a),(11b)or (11c): x is selected from the group consisting of allkyl,aryl,(ch2)m,or1,(ch2)msr1 and (ch2)mnr1r2 wherein m is an integer of 0 to 6,and r1 and r2 are hydrgen, lower alkyl, aryl or together with nitrogen form a 5-7 membered ring; q is an integer of 0 to 2; n represents the integer 1 or 2; p is an integer of 1 to 6; y and w are selected from the group consisting of alkyl, aryl, alkoxy, and amino, q is oxygen or sulfur, p is phosphorus; j represents the atoms necessary to complete a 5 to 6 membered aromatic ring; and the pharmaceutically acceptable salts thereof; their use as topoisomerase inhibitors, their preparation; and their use in the treatment of cancer

公开(公告)号：SI9300591A

公开(公告)日：1994-06-30

申请号：SI9300591

申请日：1993-11-11

Applicant: GLAXO INC

Inventor： LACKEY KAREN ,  LUZZIO MICHAEL JOSEPH ,  EVANS MICHAEL GLENN ,  BESTERMAN JEFFREY MARK ,  STERNBACH DANIEL DAVID ,  PEEL MICHAEL ROBERT

IPC: A61K31/47 ,  A61K31/675 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07F9/6561 ,  A61K31/435

Abstract: The present invention relates to water soluble, camptothecin derivatives of formula (I). wherein A represents a moiety of the formula (IIA), (IIB) or (IIC): X is selected from the group consisting of alkyl, aryl, (CH2)mOR1, (CH2)mSR1 and (CH2)mNR1R2 wherein m is an integer of 0 to 6, and R1 and R2 are hydrogen, lower alkyl, aryl or together with the nitrogen form a 5-7 membered ring; q is an integer of 0 to 2; n represents the integer 1 or 2; p is an integer of 1 to 6; Y and W are selected from the group consisting of alkyl, aryl, alkoxy, aryloxy and amino, Q is oxygen or sulfur; P is phosphorus; J represents the atoms necessary to complete a 5 or 6 membered aromatic ring; and the pharmaceutically acceptable salts thereof; their use as topoisomerase inhibitors, their preparation; and their use in the treatment of cancer.

公开(公告)号：AU5604594A

公开(公告)日：1994-06-08

申请号：AU5604594

申请日：1993-11-10

Applicant: GLAXO INC

Inventor： BESTERMAN JEFFREY MARK ,  EVANS MICHAEL GLENN ,  LACKEY KAREN ELIZABETH ,  LUZZIO MICHAEL JOSEPH ,  PEEL MICHAEL ROBERT ,  STERNBACH DANIEL DAVID

IPC: A61K31/47 ,  A61K31/675 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07F9/6561

Abstract: The present invention relates to water soluble, camptothecin derivatives of formula (I). wherein A represents a moiety of the formula (IIA), (IIB) or (IIC): X is selected from the group consisting of alkyl, aryl, (CH2)mOR1, (CH2)mSR1 and (CH2)mNR1R2 wherein m is an integer of 0 to 6, and R1 and R2 are hydrogen, lower alkyl, aryl or together with the nitrogen form a 5-7 membered ring; q is an integer of 0 to 2; n represents the integer 1 or 2; p is an integer of 1 to 6; Y and W are selected from the group consisting of alkyl, aryl, alkoxy, aryloxy and amino, Q is oxygen or sulfur; P is phosphorus; J represents the atoms necessary to complete a 5 or 6 membered aromatic ring; and the pharmaceutically acceptable salts thereof; their use as topoisomerase inhibitors, their preparation; and their use in the treatment of cancer.

公开(公告)号：AP9400638A0

公开(公告)日：1995-10-28

申请号：AP9400638

申请日：1994-04-28

Applicant: GLAXO INC

Inventor： LUZZIO MICHAEL JOSEPH ,  BESTERMAN JEFFREY M ,  EVANS MICHAEL GLENN ,  MYERS PETER LESLIE

IPC: A61K20060101 ,  A61K31/47 ,  A61P35/00 ,  C07D20060101 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22

Abstract: The present invention relates to water soluble, camptothecin derivatives of formula (1)wherein n represents the integer 1 or 2; and r1 represents hydrogen, lower alkyl, (c3-7)cycloalkyl, (c3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, amino lower alkyl, lower alkylamino lower alkyl, amino lower alkul, lower alkoxy lower alkyl or (ch2)tar wherein: t is 0 to 5 and ar represents phenyl, furyl, pyridyl, n-methylpyrrolyl, imidazolyl; or phenyl, furyl, pyridyl, n-methylpyrrolyl, imidazolyl, with one or more substituents independtly selected from hydroxy, methoxy, halogen and amino; and r2 represents diphenylmenthyl or (ch2)tar; or r1 and r2 taken together with the linking nitrogen represents n-tetrahydroquinolyl or n-tetrahydroisoquinolyl; and pharmaceutically acceptable salts and solvents thereof; their use as topoisomerase inhibitors; their preparations; and their use in the treatment of cancer.

公开(公告)号：PE52894A1

公开(公告)日：1995-01-06

申请号：PE24106194

申请日：1994-04-27

Applicant: GLAXO INC

Inventor： LUZZIO MICHAEL JOSEPH ,  MYERS PETER LESLIE ,  BESTERMAN JEFFREY MARK ,  EVANS MICHAEL GLENN

IPC: A61K31/435 ,  A61K20060101 ,  A61K31/365 ,  A61K31/47 ,  A61P35/00 ,  C07D20060101 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22

Abstract: SE REFIERE A UN COMPUESTO DE FORMULA I DONDE: 1) n VARIA DE 1 A 2; 2) R1 ES H, ALQUILO INFERIOR, CICLOALQUILO C3-C7, (CICLOALQUILO C3-C7)-ALQUILO INFERIOR, ALQUENILO INFERIOR, HIDROXIALQUILO INFERIOR, (CH2)t-Ar, DONDE t VARIA DE CERO A 5 Y Ar ES FENILO, FURILO, PIRIDILO, N-METILPIRROLILO, IMIDAZOLILO, SOLO O CON 1 o MAS SUSTITUYENTES COMO OH, OCH3, HALOGENO, AMINO; 3) R2 ES DIFENILMETILO, (CH2)t-Ar; o R1 Y R2 JUNTO CON EL ATOMO DE NITROGENO FORMAN N-TETRAHIDROQUINOLILO, N-TETRAHIDROISOQUINOLILO; EL CUAL A DIFERENCIA DE LA CAMPTOTECINA ES SOLUBLE EN AGUA Y PUEDE TENER ACTIVIDAD INHIBITORIA DE LA TOPOISOMERASA I - DNA IN VITRO Y ACTIVIDAD ANTITUMORAL IN VIVO

公开(公告)号：ZA938385B

公开(公告)日：1994-08-09

申请号：ZA938385

申请日：1993-11-10

Applicant: GLAXO INC

Inventor： LACKEY KAREN ,  LUZZIO MICHAEL JOSEPH ,  EVANS MICHAEL GLENN ,  BESTERMAN JEFFREY MARK ,  STERNBACH DANIEL DAVID ,  PEEL MICHAEL ROBERT

IPC: A61K20060101 ,  C07D20060101 ,  C07D ,  A61K