Patent RU-2119482-C1 (RU)
Title: Acridine derivatives, method of synthesis, pharmaceutical composition and a method of treatment of patients with malignant tumors
Inventor: DUMAITRE BERNARD ANDRE
IPC: A61P43/00
Filed: 1992-01-07
Granted: 1998-09-27
Abstract: FIELD: organic chemistry and technology, pharmacy. SUBSTANCE: invention proposes derivatives of acridine of the formula (I):   where R 0  means hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, amino-, nitro-group; ρ means 1 or when R 0  means C 1 -C 4 -alkoxy then ρ means 2 or 3; R 1  means hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio; R 2  means hydrogen, C 1 -C 4 -alkyl; A means oxygen, sulfur, bond, group -(CH 2 ) l NR 9 , where l means 0 or 1, and R 9  means hydrogen or methyl; B means C 1 -C 4 -alkylene optionally substituted with hydroxyl group except for that hydroxyl group and part of A can not be bound with the same carbon atom when A means oxygen or sulfur atom, or group (CH 2 ) l R 9 ,, or when A means bond then B means C 2 -C 4 -alkylene chain; R 3  means hydrogen, C 1 -C 4 -alkyl; m = 1 or 2; R 4  means hydrogen or halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio; R 5  means hydrogen, C 1 -C 4 -alkoxy; R 6  means hydrogen, C 1 -C 4/  -alkyl, C 1 -C 4 -alkoxy; R 7  means hydrogen, or R 3  and R 7  form together group -(CH 2 ) n - where n = 1 or 2; R 8  means hydrogen, C 1 -C 4 -alkoxy being group of the formula (a):   is bound with benzene ring at position 3 or 4 with respect to carboxamide substituent at condition that when group is bound to benzene ring at position 3 then R 6  should be at position 6 of benzene ring, or its physiologically acceptable salts. Invention proposes also derivatives of acridine of the formula (Ia):   where R 0  means hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy; R 1  means hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy; R 2  means hydrogen; A means oxygen, sulfur, bond; B means nonsubstituted C 1 -C 4 -alkylene chain; R 4  and R 5  are similar and mean C 1 -C 4 -alkoxy, or their physiologically acceptable salts. Derivatives of acridine of the general formula (I) are synthesized by interaction of compound (II):   where values   are given above with compound (III):   where values A, B, R 3 -R 8  are given above in the presence of coupling reaction agent. Further, physiologically compatible salts of compound (I) can be obtained also. Derivative of acridine of the general formula (I) can be synthesized by interaction of compound of the formula (IV)   where values R 0 , R 1 , R 2 , R 6 , A, B, p are given above; Q means halogen atom with compound of the formula (V):   or its salt where values R 3 -R 5 , R 7 , R 8 , are given above in the presence of an acid acceptor. Physiologically compatible salts of compound (I) can be obtained also. Invention can be used in medicine to enhance sensitivity of multiple-resistant cancer cells to chemiotherapeutic agents. Method of tumor destruction involves its treatment with compound of the formula (I) or (Ia) or their salts. Pharmaceutical composition has the above indicated compounds. Composition can be made as peroral, buccal, parenteral or rectal forms. EFFECT: improved methods of synthesis, enhanced effectiveness of compounds synthesized. 12 cl, 138 ex