公开(公告)号：JP2000109475A

公开(公告)日：2000-04-18

申请号：JP31294099

申请日：1999-11-02

Applicant: GLAXO INC

Inventor： LUZZIO MICHAEL J ,  BESTERMAN JEFFREY M ,  EVANS MICHAEL G ,  MYERS PETER LESLIE

IPC: A61K31/47 ,  A61K31/435 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07D498/22

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful as an intermediate for producing a water-soluble camptothecin derivative used for treating tumors. SOLUTION: A compound of formula I [(n) is 1 or 2; R1, R2 are each H, a 1-6C alkyl or the like, or R1 is H, a 1-6C alkyl or the like and R2 is a group of the formula; COR3, or R1 and R2 are bonded to each other together with a nitrogen atom bonded thereto to form a saturated three to seven-membered heterogeneous group; R3 is H, a 1-6C alkyl or the like; Y is O, S or the like], for example, 2'-amino-4',5'-methylenedioxy-2-trifluoroacetamidoacetophenone. The compound of formula I is obtained by reacting a compound of formula III (X is a halogen) (for example, 2'-amino-4',5'-methylenedioxy-2- chloroacetophenone) with a compound of the formula: HNR1R2 (for example, trifluoroacetamine) in the presence of a base in an aprotic polar solvent such as acetonitrile.

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：OA09767A

公开(公告)日：1993-11-30

申请号：OA60295

申请日：1992-10-28

Applicant: GLAXO INC

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

IPC: A61K31/435 ,  A61K31/47 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07D498/22

Abstract: The invention relates to water soluble, camptothecin derivatives of formula (I), wherein: n represents the integer 1 or 2; and i) R and R represent independently, hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; ii) R represents hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R represents -COR wherein R represents hydrogen, lower alkyl, perhalo-lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl; or iii) R and R taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) wherein: Y represents O, S, CH , NR4 wherein R4 represents hydrogen, lower alkyl, perhalo-lower alkyl, aryl, aryl substituted with one or more lower alkyl, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl groups or; -COR5 wherein R5 represents hydrogen, lower alkyl, perhalo-lower alkyl, lower alkoxy, aryl, aryl substituted with one or more lower alkyl, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups; and the pharmaceutically acceptable salts thereof; their use in the treatment of tumors and methods of their preparation.

公开(公告)号：MX9206211A

公开(公告)日：1993-05-01

申请号：MX9206211

申请日：1992-10-28

Applicant: GLAXO INC

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

IPC: A61K31/435 ,  A61K31/47 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07D498/22 ,  C07G5/00

Abstract: The invention relates to water soluble, camptothecin derivatives of formula (I), wherein: n represents the integer 1 or 2; and i) R and R represent independently, hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; ii) R represents hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R represents -COR wherein R represents hydrogen, lower alkyl, perhalo-lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl; or iii) R and R taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) wherein: Y represents O, S, CH , NR4 wherein R4 represents hydrogen, lower alkyl, perhalo-lower alkyl, aryl, aryl substituted with one or more lower alkyl, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl groups or; -COR5 wherein R5 represents hydrogen, lower alkyl, perhalo-lower alkyl, lower alkoxy, aryl, aryl substituted with one or more lower alkyl, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups; and the pharmaceutically acceptable salts thereof; their use in the treatment of tumors and methods of their preparation.

公开(公告)号：FI104373B

公开(公告)日：2000-01-14

申请号：FI924878

申请日：1992-10-28

Applicant: GLAXO INC

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

IPC: A61K31/435 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/47 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07D498/22

Abstract: The invention relates to water soluble, camptothecin derivatives of formula (I), wherein: n represents the integer 1 or 2; and i) R and R represent independently, hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; ii) R represents hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R represents -COR wherein R represents hydrogen, lower alkyl, perhalo-lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl; or iii) R and R taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) wherein: Y represents O, S, CH , NR4 wherein R4 represents hydrogen, lower alkyl, perhalo-lower alkyl, aryl, aryl substituted with one or more lower alkyl, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl groups or; -COR5 wherein R5 represents hydrogen, lower alkyl, perhalo-lower alkyl, lower alkoxy, aryl, aryl substituted with one or more lower alkyl, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups; and the pharmaceutically acceptable salts thereof; their use in the treatment of tumors and methods of their preparation.

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：SI9300183A

公开(公告)日：1994-12-31

申请号：SI9300183

申请日：1993-04-07

Applicant: GLAXO INC

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

IPC: A61K31/47 ,  C07D317/66 ,  C07D319/18 ,  C07D405/10 ,  C07D413/10 ,  C07D417/10 ,  C07D491/22

公开(公告)号：HUT65719A

公开(公告)日：1994-07-28

申请号：HU9203384

申请日：1992-10-28

Applicant: GLAXO INC

Inventor： BESTERMAN JEFFREY M ,  EVANS MICHAEL G ,  MYERS PETER LESLIE ,  LUZZIO MICHAEL J

IPC: A61K31/435 ,  A61K31/4738 ,  A61K31/47 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07D498/22

Abstract: The invention relates to water soluble, camptothecin derivatives of formula (I), wherein: n represents the integer 1 or 2; and i) R and R represent independently, hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; ii) R represents hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R represents -COR wherein R represents hydrogen, lower alkyl, perhalo-lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl; or iii) R and R taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) wherein: Y represents O, S, CH , NR4 wherein R4 represents hydrogen, lower alkyl, perhalo-lower alkyl, aryl, aryl substituted with one or more lower alkyl, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl groups or; -COR5 wherein R5 represents hydrogen, lower alkyl, perhalo-lower alkyl, lower alkoxy, aryl, aryl substituted with one or more lower alkyl, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups; and the pharmaceutically acceptable salts thereof; their use in the treatment of tumors and methods of their preparation.

公开(公告)号：FI924878A

公开(公告)日：1993-04-30

申请号：FI924878

申请日：1992-10-28

Applicant: GLAXO INC

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

IPC: A61K31/47 ,  A61K31/435 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07D498/22

Abstract: The invention relates to water soluble, camptothecin derivatives of formula (I), wherein: n represents the integer 1 or 2; and i) R and R represent independently, hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; ii) R represents hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R represents -COR wherein R represents hydrogen, lower alkyl, perhalo-lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl; or iii) R and R taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) wherein: Y represents O, S, CH , NR4 wherein R4 represents hydrogen, lower alkyl, perhalo-lower alkyl, aryl, aryl substituted with one or more lower alkyl, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl groups or; -COR5 wherein R5 represents hydrogen, lower alkyl, perhalo-lower alkyl, lower alkoxy, aryl, aryl substituted with one or more lower alkyl, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups; and the pharmaceutically acceptable salts thereof; their use in the treatment of tumors and methods of their preparation.

公开(公告)号：FI924878A0

公开(公告)日：1992-10-28

申请号：FI924878

申请日：1992-10-28

Applicant: GLAXO INC

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

IPC: A61K31/47 ,  A61K31/435 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07D498/22

Abstract: The invention relates to water soluble, camptothecin derivatives of formula (I), wherein: n represents the integer 1 or 2; and i) R and R represent independently, hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; ii) R represents hydrogen, lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R represents -COR wherein R represents hydrogen, lower alkyl, perhalo-lower alkyl, (C PI 1/2 )cycloalkyl, (C PI 1/2 )cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl; or iii) R and R taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) wherein: Y represents O, S, CH , NR4 wherein R4 represents hydrogen, lower alkyl, perhalo-lower alkyl, aryl, aryl substituted with one or more lower alkyl, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl groups or; -COR5 wherein R5 represents hydrogen, lower alkyl, perhalo-lower alkyl, lower alkoxy, aryl, aryl substituted with one or more lower alkyl, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups; and the pharmaceutically acceptable salts thereof; their use in the treatment of tumors and methods of their preparation.