New quaternary aromatic nitrogen heterocycle derivatives that fix the G-quadruplex structure of DNA or RNA are telomerase inhibitors, useful in the treatment of cancers and some genetic disorders

摘要

Compounds that fix the G-quadruplex structure of DNA or RNA (IB), their isomers, racemates, enantiomers, diastereoisomers, and their salts are new : Compounds that fix the G-quadruplex structure of DNA or RNA, and having the general formula (IB): aromatic ring containing N in quaternary form - (NR 3>) p- CO-divider - (CO) m-(NR' 3>) q-X-aromatic or non-aromatic ring their isomers, racemates, enantiomers, diastereoisomers, and their salts are new. m, p, q : 0 or 1; aromatic ring containing N in quaternary form : quinoline (optionally substituted by N(R a>)(R b>), 1-4C alkyl or alkoxy) in which the ring N is quaternized 1-4C alkyl, optionally substituted by OH, carboxy, 1-4C alkoxy or alkylthio, amino, alkylamino, or dialkylamino, a quinoline group substituted by at least one group N(R a>)(R b>) or alkyl or alkoxy of 1 - 4 C atoms, or quinoline having a quaternary N atom, a benzamidine, a pyridine or phenyl optionally substituted by halogen, alkoxy, CN, carbonylamino optionally substituted by one or more alkyl groups, guanyl, alkylthio, amino, alkylamino, dialkylamino, nitro, alkyleneamino, or alkenyleneamino, or an aromatic or non-aromatic mono-, di- or tricyclic heterocyclic group having 0 - 2 heteroatoms per ring but having at least one hetero atom and optionally substituted by alkylene or alkenylene groups of up to 4 C atoms and the heteroatom is quaternized N; R a>, R b>H or 1-4C alkyl; R 3>and R' 3>h, 1-4C alkyl or aralkyl; X : a simple bond, 1-4C alkyl2-4C alkenyl or alkynyl, or phenyl; the divider : 5 or 6 membered heterocycle containing N, S, or O, phenyl, diazine or triazine these being optionally substituted by halogens, alkyl, thio, oxy, or amino, themselves optionally substituted by 1-4C alkyl with the proviso that when X is a bond, the divider is phenyl optionally substituted by NH 2, m, p, and q = 1, and R 3>and R' 3>are H, then in the aromatic N heterocycle, the aromatic ring is neither unsubstituted quinoline nor quinoline substituted on the N atom by alkyl, and when the divider is a triazine and p and q are both 1, then m is not 0. ACTIVITY : Cytostatic; Muscular-Gen; Dermatological; Vasotropic; Endocrine-Gen. MECHANISM OF ACTION : Telomerase inhibitors.