Multisubstituted 1-hydroxy-9-acridones with anticancer activity

A method for synthesizing a compound having the structure:

• ##STR29## wherein R.sup.2 and R.sup.3 are the same or different and are hydrogen, a saturated or unsaturated alkyl group having 1 to 5 carbon atoms, a hydroxy group, a saturated or unsaturated alkyloxy group having 1 to 5 carbon atoms, an O-alkyloxyalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an O-benzyloxyalkyl group with the alkyl having 1 to 5 carbon atoms, an O-acetyl group, an O-benzoyl group, or an O-benzyl group;
• R.sup.4 is hydrogen, a saturated or unsaturated alkyl group having 1 to 5 carbon atoms, a hydroxy group, a hydroxymethyl group, a saturated or unsaturated alkyloxy group having 1 to 5 carbon atoms, an O-alkyloxyalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an O-benzyloxyalkyl group with the alkyl having 1 to 5 carbon atoms, an O-alkyloxyalkyloxyalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an O-acetyl group, an O-benzoyl group, or an O-benzyl group;
• wherein
• R.sup.5, R.sup.6 and R.sup.7 are the same or different and are hydrogen, a saturated or unsaturated alkyl group having 1 to 5 carbon atoms, sulfate, phosphate, a hydroxy group, a saturated or unsaturated alkyloxy group having 1 to 5 carbon atoms, an O-alkyloxyalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an O-benzyloxyalkyl group with the alkyl having 1 to 5 carbon atoms, an O-acetyl group, an benzoyl group, a nitro group, an amino group, an N-alkylamino group having 1 to 5 carbon atoms, an N,N-dialkylamino group with each alkyl having 1 to 5 carbon atoms, an aminoalkyloxy group having 1 to 5 carbon atoms, an N-alkyl-aminoalkyloxy group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an N,N-dialkyl-aminoalkyloxy group wherein each alkyl is the same or different having 1 to 5 carbon atoms, a quaternary ammonium alkyloxy salt, or a halogen;
• and
• R.sup.10 is hydrogen, a saturated or unsaturated alkyl group having 1 to 5 carbon atoms, aminoalkyl group having 1 to 5 carbon atoms, an N-alkylaminoalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an N,N-dialkylaminoalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, or an amino acid moiety;
• which comprises:
• (a) combining a compound having the structure:
• ##STR30## wherein R.sup.5, R.sup.6 and R.sup.7 are the same as defined previously;
• and
• X is F, Cl, Br, or I;
• with a compound having the structure:
• ##STR31## respectively, wherein the molar ratio of the compound of formula II to the compound of formula IV or of the compound of formula III to the compound of formula V is about 1 to 5 and R.sup.2, R.sup.3 and R.sup.4 are the same as defined previously;
• and
• X is F, Cl, Br, or I or a nitro group;
• under Ullman condensation conditions so as to form a compound having the structure:
• ##STR32## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are the same as defined previously;
• (b) treating the compound formed in step (a) under cyclization conditions so as to form a compound having the structure:
• ##STR33## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are the same as defined previously;
• (c) treating the compound formed in step (b) under N-alkylating conditions so as to form a compound having the structure:
• ##STR34## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.10 are the same as defined previously;
• and
• (d) treating the compound formed in step (c) under de-O-methylating conditions so as to form a compound having the structure:
• ##STR35## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.10 are the same as defined previously.