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：AU1231492A

公开(公告)日：1992-08-27

申请号：AU1231492

申请日：1992-01-24

Applicant: GLAXO INC

Inventor： LUZZIO MICHAEL J ,  BESTERMAN JEFFREY M ,  EVANS MICHAEL G ,  ROSS JOHNSON M

IPC: C07D491/04 ,  C07D491/056 ,  A61K31/47

Abstract: The present invention relates to the compounds of formula (I), wherein: R is hydrogen, hydroxy or amino; R is hydrogen, hydroxy, methoxy or methoxymethoxy; R is hydrogen, hydroxy, amino, methoxy, methoxymethoxy or, taken together with R , methylenedioxy (also known as 1,3 dioxolo); R is hydrogen, hydroxy, methoxy, methoxymethoxy, benzyl, di(C1-4)alkylaminomethyl or, taken together with R , methylenedioxy; R is hydrogen or hydroxy; provided that at least one of R through R is other than hydrogen; and i) X is hydroxy or methoxy with X , X and X being hydrogen; or ii) X taken together with X , X taken together with X or X taken together with X , is methylenedioxy, provided that each of the remaining respective X , X , X and X substituents are hydrogen, intermediates in the synthesis of them, pharmaceutical formulation containing them, their use as inhibitors of topoisomerase and their use in the treatment of tumors.

公开(公告)号：SK323792A3

公开(公告)日：1998-09-09

申请号：SK323792

申请日：1992-10-27

Applicant: GLAXO INC

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

IPC: A61K31/435 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/47 ,  A61K31/5377 ,  A61K31/541 ,  A61P35/00 ,  A61P43/00 ,  C07D317/66 ,  C07D319/18 ,  C07D491/22 ,  C07D498/22 ,  A61K31/33

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：PL173684B1

公开(公告)日：1998-04-30

申请号：PL29870593

申请日：1993-04-26

Applicant: GLAXO INC

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

IPC: C07D491/12 ,  C07D491/22

公开(公告)号：CA2081580A1

公开(公告)日：1993-04-30

申请号：CA2081580

申请日：1992-10-28

Applicant: GLAXO INC

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

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 ,  C07D405/06 ,  C07D413/06 ,  C07D417/06 ,  A61K31/495 ,  A61K31/535 ,  A61K31/54

Abstract: GLX-76/AC155 WATER SOLUBLE CAMPTOTHECIN DERIVATIVES The invention relates to water soluble, camptothecin derivatives of formula (1), (I) wherein: n represents the integer 1 or 2; and i) R1 and R2 represent independently, hydrogen, lower alkyl, (C3 7)cycloalkyl;(C3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; ii) R1 represents hydrogen, lower alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R2 represents -COR3 wherein R3 represents hydrogen, lower alkyl, perhalo-lower alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy, lower alkoxy lower alkyl; or iii) R1 and R2 taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) wherein: Y represents O, S, CH2, 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：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.