公开(公告)号：GB2280674A

公开(公告)日：1995-02-08

申请号：GB9415663

申请日：1994-08-03

Applicant: GLAXO INC

Inventor： LUZZIO MICHAEL JOSEPH ,  STERNBACH DANIEL DAVID ,  UEHLING DAVID E ,  PROFETA JUNIOR SALVATORE

IPC: C07D491/22 ,  A61K31/435

Abstract: Camptothecin derivatives of formula (I> wherein R is hydrogen, alkyl, alkenyl or phenyl; Q is hydrogen, halogen, cyano, 5-tetrazolo, -COOR , -CONR R , -C(NH2)=NR , -CH=NNH2, -(CH2)nR , -CH=CH(CH2)nR or -C=C(CH2)nR wherein n is 0, 1, 2 or 3; R is hydrogen or alkyl; R and R independently represent hydrogen, alkyl, aminoalkyl or dialkylaminoalkyl; R is hydrogen, alkyl, hydroxy, alkoxy or -COOCH2NHCOO Bu; R is hydrogen, hydroxy, -NR R , -NHCOR or a nitrogen heterocycle of formula wherein R and R independently represent hydrogen or alkyl; R is alkyl or O-alkyl; Y is O, S, NR , CH2 or a direct linkage; R is hydrogen or alkyl; T is hydrogen or when Q is halogen T may also represent halogen; and X is a free electron pair, oxygen or alkyl; and pharmaceutically acceptable salts thereof, are topoisomerase inhibitors useful in the treatment of cancer. Pyridines of formula (II> wherein R* is methyl or ethyl Q is Br and T is H or Br; and derivatives corresponding to formula (I) but with the E ring open are novel intermediates.