US 8,999,955 B2Granted

Tetrahydrocyclopenta[c]acridine derivatives as kinase inhibitors and biological

AssigneeCentre National De La Recherche Scientifique

InventorsPhilippe Olivier Belmont, Laurent Meijer, Philip Cohen, Amaury Patin, Johann Bosson, Peter Gregory Goekjian

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Abstract

The invention relates to kinase inhibitors of the formula (I) in which —R1 to R4═H; ether or polyether, amino; NO2; NH-carbamate; NH—CO—R, with R such as defined above; N3 and derivatives thereof of the 1,2,3-triazole type; —R5=—OH; halogen; —OR with R such as defined above; OH-carbamate; OH-carbonate; NH2, NH-carbamate; NH—CO—R, with R such as defined above; N3 and derivatives thereof of the 1,2,3-triazole type; N(R9,R10); —R5′═H or a C1-C12 alkyl, —R6═H; R; (R or R′)3—Si, with R such as defined above; optionally substituted aryl, heteroaryl; halogen (iodine); alkynyl; —R7 and R8═H, C1-C12 alkyl; —R9 and R10═H, R (or R′) such as defined above. These compounds can be used as kinase inhibitors in particular for treating cancer.

Claims15

Dependent claims

A kinase inhibitor compound of formula (I)

in which:
R1 to R4, which may be identical or different, represent H;
an ether radical —OR, wherein R represents a linear or branched C1-C12 alkyl radical;
an amino group NH2 or N(R9, R10);
NO2;
NH-carbamate of —NH—CO-OM type, with M representing R or a salt;
NH—CO—R;
N3 or derivatives thereof with a 1,2,3-triazole cycle;
R5 represents an —OH group;
halogen;
—OR with R as defined above with respect to R1-R4;
OH-carbamate of —O—CO—NHM type, with M representing R, as defined above with respect to R1-R4;
OH-carbonate of —O—CO-OM type, with M representing R, as defined above with respect to R1-R4;
NH2, NH-carbamate of —NH—CO-OM type, with M representing R, or a salt;
NH—CO—R with R as defined above with respect to R1-R4;
N3 or derivatives thereof with a 1,2,3-triazole cycle;
or N(R9, R10);
R5′ represents H or a C1-C12 alkyl radical,
or R5/R5′ together represents an ═O group;
R6 represents H;
the R radical;
an (R or R′)3—Si group, R being as defined above with respect to R1-R4;
an aryl radical, where appropriate substituted, a heteroaryl radical;
a halogen;
or an alkynyl radical —C≡C—R;
R7 and R8, which may be identical or different, represent an H or a C1-C12 alkyl radical;
R9 and R10, which may be identical or different, represent H or the R-radical, with the exception of the compounds in which R1-R4, R7 and R8═H, R5 and R5′ form a —C═O group, and R6═—(CH3)3—Si, —C6H5, or C1 or C4 alkyl;
R1-R4, R7 and R8═H, R5═OH and R5′═H, and R6=—(CH3)3—Si, —C6H5, or C1 or C4 alkyl;
R1-R4, R7 and R8═H, R5═H and R5′═OH, and R6=—(CH3)3—Si, —C6H5, or C1 or C4 alkyl;
R1-R4, R7 and R8═H, R5=—OCH3 and R5′═H, and R6═C4 alkyl;
and R1-R4, R7 and R8═H, R5═H and R5′=—OCH3, and R6═C4 alkyl.

28 more elements

A pharmaceutical composition comprising a therapeutically effective amount of at least one compound formula (I)

in which:
R1 to R4, which may be identical or different, represent H;
an ether radical —OR, wherein R represents a linear or branched C1-C12 alkyl radical;
an amino group NH2 or N(R9, R10);
NO2;
NH-carbamate of —NH—CO-OM type, with M representing R or a salt;
NH—CO—R;
N3 or derivatives thereof with a 1,2,3-triazole cycle;
R5 represents an —OH group;
halogen;
—OR with R as defined above with respect to R1-R4;
OH-carbamate of —O—CO—NHM type, with M representing R as defined above with respect to R1-R4;
OH-carbonate of —O—CO-OM type, with M representing R as defined above with respect to R1-R4;
NH2, NH-carbamate of —NH—CO-OM type, with M representing R or a salt;
NH—CO—R with R as defined above with respect to R1-R4;
N3 or derivatives thereof with a 1,2,3-triazole cycle;
or N(R9, R10), M and R being as defined above with respect to R5;
R5′ represents H or a C1-C12 alkyl radical,
or R5/R5′ together represents an ═O group;
R6 represents H;
the R radical;
an (R or R′)3—Si group;
an aryl radical, where appropriate substituted, a heteroaryl radical;
a halogen;
or an alkynyl radical —C≡C—R, with R as defined above with respect to R1-R4;
R7 and R8, which may be identical or different, represent an H or a C1-C12 alkyl radical;
R9 and R10, which may be identical or different, represent H or the R radical, and a pharmaceutically acceptable carrier;
said composition being in an orally administrable, parenterally administrable or injectable form.

25 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/735,463Filed 19 Jan 2009
Priority: FR 08 0027518 Jan 2008
Published: US 2010/0285124 A111 Nov 2010
Granted: 7 Apr 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 219/04
Heterocyclic compounds containing acridine or hydrogenated acridine ring systems: with hetero atoms or with carbon atoms having three bonds to…
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/18
Drugs for disorders of the nervous system: antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia