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US 2016/0280653 A1Published application
Quinolines derivatives as novel anticancer agents
AssigneeGenoscience Pharma
InventorsJerome COURCAMBECK, Philippe HALFON, Firas BASSISSI, Sonia BRUN, Gregory NICOLAS, Antoine BERET, Serge PETIT, Claire CAMUS, Jean Pierre NALLET
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Abstract
The invention provides quinoline derivatives, their manufacture, pharmaceutical compositions containing them, and their use as medicaments. The active compounds of the present invention are useful for the treatment of proliferative neoplastic and non-neoplastic diseases.
Claims31
A compound of formula (I)
- wherein
- R1 is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroaromatic 5 to 9-membered ring comprising 1, 2 or 3 heteroatoms independently selected from O, N, and S;
- R2 is selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, nitro or NR7R8, NR7—(CO)—R8, NR7—(CO)—O—R, NR7—(CO)—NR7R8, O—(CO)R7, O—(CO)—O—R7, O—(CO)—NR7R8, (CO)R7, (CO)—O—R7, (CO)—NR7R8, SO2—R7, SO2NR7R8, NR7—SO2—R8, with R7 and R8 representing independently hydrogen, C1-C6 alkyl, phenyl (optionally substituted with one or more substituent groups selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, cyano, nitro or NR7R) or benzyl (optionally substituted with one or more substituent groups selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, cyano, nitro or NR7R8), alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl aryl and heteroaryl;
- L1 is selected from a bond or from optionally substituted C1-C14alkyl(-R3), N(—R3), C═O, (CO)—O, (CO)—NR7, and O;
- n is 0, 1, 2, 3 or 4;
- W is selected from:
- wherein
- L2 is selected from a bond or from optionally substituted C1-C14alkyl(-R3), N(—R3), C═O, (CO)—O, (CO)—NR7, and O;
- wherein R3 is selected from H, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted C1-C8-alkyl, optionally substituted C2-C8-alkenyl, optionally substituted C2-C8-alkynyl, optionally substituted C3-C12 cycloalkyl, and optionally substituted C3-C12 cycloalkenyl;
- and wherein R7 is as defined above;
- R4 and R5 are independently selected from hydrogen, C1-C6 alkyl or phenyl (optionally substituted with one or more substituent groups selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, cyano, nitro or NR7R8) or benzyl (with the phenyl group optionally substituted with one or more substituent groups selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, cyano, nitro or NR7R8) or CH2—CH2-Phenyl (with the phenyl group optionally substituted with one or more substituent groups selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, cyano, nitro or NR7R8), (CO)—R7, (CO)—OR7, (CO)—NR7R8, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, monocyclic or bicyclic heteroaryl or R4 and R5 are linked to form a heterocyclic group;
- R6 is selected from H, C1-C6 alkyl, monocyclic or bicyclic cycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
- wherein the term “optionally substituted” means optionally substituted with one or more substituents independently selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, cyano, nitro or NR7R8with R7 and R8 representing independently hydrogen, C1-C6 alkyl, phenyl (optionally substituted with one or more substituent groups selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, cyano, nitro or NR7R8) or benzyl (optionally substituted with one or more substituent groups selected from Cl, F, I, Br, C1-C6 alkyl, C1-C6 alkyl substituted with one or more halogens, C1-C6 alkoxy, hydroxy, cyano, nitro or NR7R8), alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl aryl and heteroaryl;
- and any pharmaceutically acceptable salt, solvate or prodrug thereof.
11 more elements
(canceled)
A method according to claim 30, wherein the proliferative and/or neoplastic disease is selected from the group consisting of:
- carcinoma;
- cancer of the esophagus, head, kidney, liver, lung, nasopharyngeal, neck, ovary, pancreas, prostate, or stomach;
- a leukemia (e.g. acute myelogenous leukemia, acute lymphocytic leukemia, acute promyelocytic leukemia (APL), acute T-cell lymphoblastic leukemia, adult T-cell leukemia, basophilic leukemia, eosinophilic leukemia, granulocytic leukemia, hairy cell leukemia, leukopenic leukemia, lymphatic leukemia, lymphoblastic leukemia, lymphocytic leukemia, megakaryocytic leukemia, micromyeloblastic leukemia, monocytic leukemia, neutrophilic leukemia and stem cell leukemia);
- a malignant lymphoma, a malignant melanoma;
- myeloproliferative diseases;
- a sarcoma;
- a tumor of the central nervous system;
- a germ-line tumor;
- testicular cancer;
- thyroid cancer;
- astrocytoma;
- colon cancer, melanoma, and a mixed type of neoplasia.
9 more elements
Dependencies are inferred from the claim text.