Asymmetrically substituted anthrapyridazone derivatives as cytostatics

Asymetrically substituted anthrapyridazone derivatives of formula (I)

• wherein
• X is oxygen or nitrogen atom,
• and
• when X is oxygen atom, then anthrapyridazone is presented by formula (IA)
• wherein only one of three substituents R1, R2 or R3 is hydrogen atom, while the two remaining substituents, have the following meaning:
• R1 is —(CH2)q—N(R4)—R5,
• where
• q=2 or 3,
• R4 and R5 together with a nitrogen atom at position 2 to which they are attached form 6-membered cyclic ring possibly including additional nitrogen or oxygen atom;
• R2 is —NH—(CH2)m—(Y)n—(CH2)p—R6,
• where
• m=0, 1, 2 or 3
• n=0, 1
• p=0, 1, 2
• Y is —N(R7)— group
• R6 is hydrogen atom or —OH, and
• R7 is hydrogen atom or —CH3, and
• R3 is H.

A method of treatment of patients, comprising administering to a patient a therapeutically effective amount of anthrapiridazone of formula (I),

• wherein
• X is oxygen or nitrogen atom,
• and
• when X is oxygen atom, then anthrapyridazone is presented by formula (IA)
• wherein only one of three substituents R1, R2or R3 is hydrogen atom, while the two remaining substituents, have the following meaning:
• R1 is (CH2)q-OH or —(CH2)q-N(R4)—R5,
• where
• q=2 or 3;
• R4 and R5 are the same and mean C1 or C3-alkyl,
• or
• R4 and R5 together with the nitrogen atom at position 2 to which they are attached form 6-membered cyclic ring optionally containing additional nitrogen or oxygen atoms, such as piperazine, piperidine or morpholine rings;
• R2 is —NH—(CH2)m-(Y)n-(CH2)p-R6,
• where
• m=1, 2 or 3
• n=1
• p=1 or 2
• Y is —C(O)— or —N(R7)—
• R6 is —OH or phenyl,
• R7 is hydrogen atom or C1-C3-alkyl,
• R3 is hydrogen atom or —NH—(CH2)r-N(R8)-R9 moiety
• where
• r=1, 2 or 3,
• R8 and R9 are the same or different and independently are H, C1-C3-alkyl or phenyl substituted with C1-C3-alkyl;
• with the provision, that
• when R1 is —(CH2)2N(CH3)2 (q=2 and R4=R5=CH3), then R2 is not —(CH2)2N(CH3)2 nor —NH2;
• and
• when X is nitrogen atom, then in formula (I)
• R3 is H,
• R2 is attached to nitrogen atom and together form the group presented by formula (a) or (b)
• R1 and R10 are the same and are —(CH2)2N(CH3)2, and
• R1 and R11 are the same and are —(CH2)2N(CH2CH3)2,
• thus anthrapyridazone has the formula (I B) or (I C)
• as well as their pharmaceutically acceptable salts.