GB9900334D0 — Tricylic vascular damaging agents

USPTO Abstract

The invention relates to the use of compounds of formula (I): wherein X is -C(O)-, -C(S)-, -C-NOH, or -CH(R<SUP>7</SUP>)- wherein R<SUP>7 </SUP>is hydrogen, hydroxy, C<SUB>1-7</SUB>alkoxy, -OR<SUP>8 </SUP>or -NR<SUP>8</SUP>R<SUP>9 </SUP>(wherein R<SUP>8 </SUP>is a group -Y<SUP>1</SUP>R<SUP>10 </SUP>(wherein Y<SUP>1 </SUP>is a direct bond, -C(O)-, -C(S)-, -S-, -C(O)O-, -C(O)NR<SUP>11</SUP>-, -SO<SUB>2</SUB>- or -SO<SUB>2</SUB>NR<SUP>12</SUP>- (wherein R<SUP>11 </SUP>and R<SUP>12</SUP>, which may be the same or different, each independently represents hydrogen; C<SUB>1-3</SUB>alkyl or C<SUB>1-3</SUB>alkoxyC<SUB>2-3</SUB>alkyl) and R<SUP>10 </SUP>is as defined herein, R<SUP>9 </SUP>includes hydrogen; R<SUP>11</SUP>, R<SUP>12 </SUP>and R<SUP>13 </SUP>are as defined herein and are preferably methyl; R<SUP>4</SUP>, R<SUP>5 </SUP>and R<SUP>6 </SUP>are as defined herein with the proviso that R<SUP>5 </SUP>is not hydroxy, alkoxy, substituted alkoxy, -OPO<SUB>3</SUB>H<SUB>2</SUB>, -O-C<SUB>1-7</SUB>alkanoyl or benzyloxy; and salts thereof in the manufacture of a medicament for use in the production of a vascular damaging effect in warm-blooded animals such as humans. The present invention further relates to compounds of the formula (I), pharmaceutical compositions containing them, processes for their preparation and to a method of treatment using the compounds to produce a vascular damaging effect in a warm-blooded animal such as a human. The compounds of formula (I) and the pharmaceutically acceptable salts thereof may be useful in the treatment of a number of disease states including cancer and rheumatoid arthritis.