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US 10,722,505 B2Granted
Substituted 2,4 diamino-quinoline as new anticancer agents
AssigneeGenoscience Pharma
InventorsFiras Bassissi, Antoine Beret, Sonia Brun, Jérôme Courcambeck, Clarisse Dubray, Gregory Nicolas, Philippe Halfon
Life of this patent
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Abstract
The present invention relates to novel 2-primary amino-4-secondary amino-quinoline derivatives, their manufacture, pharmaceutical compositions comprising them and their use as medicaments. The active compounds of the present invention are useful for the treatment and prevention of proliferative neoplastic and non-neoplastic diseases.
Claims24
A compound of formula (I)
- Wherein
- R1 is chosen from a C6-C10 aryl substituted or not by R9;
- a heteroaryl 5 to 8-membered ring comprising 1, 2, 3 heteroatoms selected from O, N and S substituted or not by R9;
- a fused heteroaryl as defined comprising from 8 to 13 atoms including 1, 2, 3, 4, heteroatoms selected from O, N and S and comprising at least 2 carbon atoms substituted or not by R9;
- L is chosen from an optionally substituted (C1-C10) alkyl;
- a (C1-C10) alkyl linear or branched substituted by R4;
- an optionally substituted (C3-C10) cycloalkyl;
- an optionally substituted (C5-C10) cycloalkenyl;
- an optionally substituted (C3-C10) alkenyl;
- an optionally substituted (C3-C10) alkynyl;
- C═O;
- SO;
- SO2;
- (C═O)—NR8;
- (C═O)—O;
- (C═O)—O—(C1-C4)alkyl;
- SO2NR8;
- NR8;
- wherein R4 is chosen from H;
- an optionally substituted (C1-C10) alkyl;
- an optionally substituted (C3-C10) alkenyl;
- an optionally substituted (C3-C10) alkynyl;
- an optionally substituted (C3-C10) cycloalkyl;
- an optionally substituted (C5-C10) cycloalkenyl;
- an optionally substituted (C8-C10) cycloalkynyl;
- an optionally substituted (C6-C10) aryl;
- an heteroaryl 5 to 8-membered ring or a fused heteroaryl as defined comprising from 8 to 13 atoms including 1, 2, 3, 4 heteroatoms selected from O, N and S and comprising at least 2 carbon atoms substituted or not with one or more substituent groups independently selected from hydrogen, halogen atom, (C1-C10) alkyl substituted with by one or more halogens atom(s), (C1-C10) alkoxy, hydroxyl, cyano, nitro, carboxy, NR8R8′, a 4 to 9-membered ring saturated or unsaturated comprising 1, 2 or until 3 heteroatoms independently selected from O, N and S;
- R2 is selected from NR5R6;
- R3 is chosen from a hydrogen atom;
- a halogen atom;
- a (C1-C10) alkyl linear or branched substituted or not by one or more halogen atom(s), hydroxyl, alkoxy-NR5R6;
- a (C2-C10) alkenyl;
- a (C2-C10) alkynyl;
- a (C3-C10) cycloalkyl;
- a (C5-C10) cycloalkenyl;
- a (C8-C10) cycloalkynyl;
- a (C1-C10) alkoxy;
- a hydroxyl;
- a nitro;
- a cyano;
- a NR5R6;
- a O—(R7);
- a (CO)—R7;
- a (CO)—O—R7;
- a (CO)—NR5R6;
- a O—(CO)—R7;
- a O—(CO)—NR5R6;
- a NR5—(CO)—R7;
- a NR5—(CO)—OR7;
- a NR5—(CO)—NR5R6;
- a —(O—CH2CH2-)m-ORn;
- a -(0-CH2CH2-)m-NR11R11;
- a SO2—R7;
- a NR5—SO2—R7;
- a SO2—NR5R6;
- a NR5—(C2-C6)-alkyl-NR5R6;
- an optionally substituted aryl;
- an optionally substituted benzyl;
- an optionally substituted heteroaryl from 5 to 8-membered ring comprising 1, 2, or 3 heteroatoms selected from O, N and S;
- an optionally substituted fused heteroaryl as defined comprising from 8 to 13 atoms including 1, 2, 3, 4 heteroatoms selected from O, N and S and comprising at least 2 carbon atoms;
- an optionally substituted heterocyclyl from 4 to 9-membered ring saturated or unsaturated comprising 1, 2 or until 3 heteroatoms independently selected from O, N and S;
- R5 and R6 are independently chosen from a hydrogen;
- an optionally substituted (C1-C10) alkyl;
- an optionally substituted (C3-C10) alkenyl;
- an optionally substituted (C3-C10) alkynyl;
- an optionally substituted (C3-C10) cycloalkyl;
- an optionally substituted (C5-C10) cycloalkenyl;
- an optionally substituted (C8-C10) cycloalkynyl;
- a (CO)—R7;
- a (CO)—O—R7;
- a (CO)—NR8R8′;
- a SO2—R7;
- a SO2—NR8R8′;
- a (C1-C10) alkyl substituted with NR8R8′;
- a (C3-C10) cycloalkyl substituted with NR8R8′;
- an optionally substituted aryl;
- an optionally substituted benzyl;
- an optionally substituted heteroaryl 5 to 8-membered ring comprising 1, 2, or 3 heteroatoms selected from O, N and S;
- an optionally substituted heterocyclyl from 4 to 9-membered ring saturated or unsaturated comprising 1, 2 or until 3 heteroatoms independently selected from O, N and S;
- or R5 and R6 is linked together with the nitrogen atom to which they are covalently linked to form a heterocyclyl group forming a 4 to 9-membered ring which may contain additional 1, 2, or 3 heteroatoms selected from O, N and S;
- R7 and R7′ are independently chosen from a hydrogen;
- an optionally substituted (C1-C10) alkyl;
- an optionally substituted (C3-C10) alkenyl;
- an optionally substituted (C3-C10) alkynyl;
- an optionally substituted (C3-C10) cycloalkyl;
- an optionally substituted (C5-C10) cycloalkenyl;
- an optionally substituted (C8-C10) cycloalkynyl;
- a C1-C10 linear or branched alkyl substituted with NR8R8;
- an optionally substituted (C6-C10) aryl, an optionally substituted benzyl, an optionally substituted heteroaromatic 5 to 8-membered ring comprising 1, 2, or 3 heteroatoms selected from O, N and S;
- R8 and R8′ are independently chosen from a hydrogen;
- an optionally substituted (C1-C10) alkyl;
- an optionally substituted (C3-C10) alkenyl;
- an optionally substituted (C3-C10) alkynyl;
- an optionally substituted (C3-C10) cycloalkyl;
- an optionally substituted (C5-C10) cycloalkenyl;
- an optionally substituted (C8-C10) cycloalkynyl;
- or R8 and R8′ is linked together with the nitrogen atom to which they are covalently linked to form a heterocyclyl group forming a 4 to 9-membered ring which may contain additional 1, 2, or 3 heteroatoms selected from O, N and S;
- R9 is independently selected from a hydrogen;
- a halogen atom;
- an optionally substituted (C1-C10) alkyl;
- an (C1-C10) alkyl linear or branched substituted by one or more halogen atom(s), a hydroxyl, an alkoxy;
- an optionally substituted (C2-C10) alkenyl;
- an optionally substituted (C2-C10) alkynyl;
- an optionally substituted (C3-C10) cycloalkyl;
- an optionally substituted (C5-C10) cycloalkenyl;
- an optionally substituted (C8-C10) cycloalkynyl;
- an optionally substituted (C1-C10) alkoxy;
- a hydroxyl;
- a nitro;
- a cyano;
- a NR5R6, a (CO)—R7;
- a (CO)—O—R7;
- a (CO)—NR5R6;
- a O—(CO)—R7;
- a O—(CO)—NR5R6;
- a NR5—(CO)—R7;
- a NR5—(CO)—OR7;
- a NR5—(CO)—NR5R6;
- a SO2—R7;
- a NR5—SO2—R7;
- a SO2—NR5R6;
- a (C1-C10) alkyl substituted with NR5R6;
- a NR5—(C2-C10)-alkyl-NR5R6;
- a —(O—CH2CH2-)m-OR11;
- a —(O—CH2CH2-)m-NR11R11′;
- an optionally substituted (C6-C10) aryl;
- an optionally substituted benzyl;
- an optionally substituted heteroaryl 5 to 8-membered ring comprising 1, 2, or 3 heteroatoms selected from O, N and S;
- an optionally substituted heterocyclyl group forming a 4 to 9-membered ring which may contain 1, 2, or 3 heteroatoms selected from O, N and S;
- a —NR5R10;
- a —O—R10;
- R10 is independently chosen from a hydrogen;
- a (C6-C12)-aryl substituted or not by R12;
- a benzyl substituted or not by R12;
- a heteroaryl from 5 to 8-membered ring comprising 1, 2, or 3 heteroatoms selected from O, N and S substituted or not by R12;
- a fused heteroaryl defined as comprising from 8 to 13 atoms including 1, 2, 3, 4 heteroatoms selected from O, N and S and comprising at least 2 carbon atom substituted or not by R12;
- a heterocyclyl forming a 4 to 9-membered ring which can contain 0, 1, 2, or 3 heteroatoms selected from O, N and S substituted or not by R12;
- R11 and R11′ is independently chosen from a hydrogen atom;
- an optionally substituted (C2-C10) alkyl;
- an optionally substituted (C3-C10) alkenyl;
- an optionally substituted (C3-C10) alkynyl;
- an optionally substituted (C3-C10) cycloalkyl;
- an optionally substituted (C5-C10) cycloalkenyl;
- an optionally substituted (C8-C10) cycloalkynyl;
- an (C2-C10) alkyl linear or branched substituted or not by one or more halogen atom(s);
- or R11 and R11′ is linked together with the nitrogen atom to which they are covalently linked to form a heterocyclyl group forming a saturated or unsaturated 4 to 9-membered ring which may contain additional 1, 2, or 3 heteroatoms selected from O, N and S;
- R12 is chosen from a hydrogen atom;
- a halogen atom;
- a (C1-C10) alkyl linear or branched substituted or not by one or more halogen atom(s), hydroxyl, alkoxy, NR11R11;
- a (C2-C10) alkenyl;
- a (C2-C10) alkynyl;
- a (C3-C10) cycloalkyl;
- a (C5-C10) cycloalkenyl;
- a (C8-C10) cycloalkynyl;
- a (C1-C10) alkoxy;
- a hydroxyl;
- a nitro;
- a cyano;
- a NR11R11;
- a O—(R7);
- a (CO)—R7;
- a (CO)—O—R7;
- a (CO)—NR11R11′ a O—(CO)—R7;
- a O—(CO)—NR11R11;
- a NR11—(CO)—R7;
- a NR11—(CO)—OR11′;
- a NR11—(CO)—NR11R11′;
- a —(O—CH2CH2-)m-OR11;
- a —(O—CH2CH2-)m-NR11R11;
- a SO2—R7;
- a NR5—SO2—R7;
- a SO2—NR11R11;
- a NR11—(C2-C6)-alkyl-NR11R11;
- an optionally substituted aryl;
- an optionally substituted benzyl;
- an optionally substituted heteroaryl from 5 to 8-membered ring comprising 1, 2, or 3 heteroatoms selected from O, N and S;
- an optionally substituted fused heteroaryl as defined comprising from 8 to 13 atoms including 1, 2, 3, 4 heteroatoms selected from O, N and S and comprising at least 2 carbon atoms;
- an optionally substituted heterocyclyl from 4 to 9-membered ring saturated or unsaturated comprising 1, 2 or until 3 heteroatoms independently selected from O, N and S;
- n can represent an equal integer which can have any one of the values 0, 1, 2, 3 or 4;
- m can represent an equal integer which can have any one of the values 1, 2 or 3;
- w can represent an equal integer which can have any one of the values 0 or 1;
- wherein the term “optionally substituted” means optionally substituted with one or more substituents independently chosen from an halogen atom, a (C1-C10) alkyl linear or branched substituted or not by one or more halogen atom(s), a (C2-C10) alkenyl linear or branched substituted or not by one or more halogen atom(s), a (C2-C10) alkynyl linear or branched substituted or not by one or more halogen atom(s), a (C3-C10) cycloalkyl substituted or not by one or more halogen atom(s), a (C5-C10) cycloalkenyl substituted or not by one or more halogen atom(s), a (C8-C10) cycloalkynyl substituted or not by one or more halogen atom(s), a (C1-C10) alkoxy, a hydroxyl, a cyano, a nitro, a NR8R8′ (with R8 and R8′ as described above);
- and any pharmaceutically acceptable salt, solvate, stereoisomers, diastereoisomers and enantiomers thereof or mixtures of stereoisomers, solvate or prodrug thereof.
180 more elements
Dependencies are inferred from the claim text.