Fused thiophene derivatives and their uses
The present invention relates to a new class of fused thiophene derivatives and their uses for treating diseases such as infection, cancer, metabolic diseases, cardiovascular diseases, iron storage disorders and inflammatory disorders.
1. A compound of formula (I):
wherein:
X represents:
—CR 1b R 1b′ ;
n is 0, 1, or 2;
R 1a , R 1a′ , R 1b , R 1b′ , R 1c , R 1c′ , R 1d , and R 1d′ represent independently:
a hydrogen,
a halogen,
a (C 1 -C 6 )alkyl, optionally substituted by at least one halogen,
a (C 1 -C 6 )alkyloxy,
a cyano, or
an aryl optionally substituted by at least one radical selected from the group consisting of:
a halogen,
a (C 1 -C 6 )alkyl optionally substituted by at least one halogen,
a hydroxy, and
a (C 1 -C 6 )alkyloxy; or
R 1a and R 1a′ , R 1b and R 1b′ , R 1c and R 1c′ , or R 1d and R 1d′ form together a cycloalkyl; or
R 1a or R 1a′ and R 1d or R 1d′ form together a bridged carbocyclyl;
and wherein at least two of R 1a , R 1a′ , R 1b , R 1b′ , R 1c , R 1c′ , R 1d , and R 1d′ are not a hydrogen;
R 2 represents —COOH;
R 3 represents:
a 5-10 membered ring, saturated or unsaturated, selected from the group consisting of:
an aryl optionally fused to a dioxole,
a heteroaryl selected from the group consisting of a pyridinyl, a pyridazinyl, a pyrimidinyl, a pyrazinyl, an imidazolyl, and a pyrazolyl,
a cycloalkyl,
a heterocycloalkyl, and
a 5-10 membered bridged carbocyclyl or heterocyclyl, said 5-10 membered ring is optionally substituted by at least one radical selected from the group consisting of:
a halogen,
a (C 1 -C 6 )alkyl optionally substituted by at least one halogen, or a (C 1 -C 6 )alkyloxy,
a —NH—(C 1 -C 6 )alkyl or a —N—((C 1 -C 6 )alkyl) 2 , optionally substituted by a heterocycloalkyl or a (C 1 -C 6 )alkyloxy,
a —NH-heterocycloalkyl, a —NH-cycloalkyl, a —N((C 1 -C 6 )alkyl)-heterocycloalkyl or a —N((C 1 -C 6 )alkyl)-cycloalkyl, optionally substituted by a (C 1 -C 6 )alkyloxy or a —CO—R 4 with R 4 being a hydrogen or a (C 1 -C 6 )alkyl,
a hydroxy,
a (C 1 -C 6 )alkyloxy optionally substituted by at least one radical selected from the group consisting of a halogen, a hydroxy, a (C 1 -C 6 )alkyloxy, a —NR 5 R 6 with R 5 and R 6 are independently a hydrogen or a (C 1 -C 6 )alkyl, a —NHCOR 7 , a —NHCO 2 R 7 , with R 7 being a (C 1 -C 6 )alkyl, a —CO 2 R 4 with R 4 being a hydrogen or a (C 1 -C 6 )alkyl, and a heterocycle,
a —NHCOR 7 or —NHCO 2 R 7 with R 7 being a (C 1 -C 6 )alkyl, and
a heterocycloalkyl, a heterocycloalkyloxy or a spiroheterocycloalkyl, optionally substituted by a (C 1 -C 6 )alkyloxy, a hydroxy, a halogen or a (C 1 -C 6 )alkyl optionally substituted by a (C 1 -C 6 )alkyloxy; and
the stereoisomers, and the pharmaceutical salts thereof; and
with the proviso that the compound of formula (I) is not 2-[(4-Chlorobenzoylamino]-6,6-dimethyl-5,7-dihydro-4H-benzothiophene-3-carboxylic acid.
2. The compound according to claim 1 , wherein R 1a , R 1a′ , R 1b , R 1b′ , R 1c , R 1c′ , R 1d , and R 1d′ represent independently a hydrogen, a (C 1 -C 6 )alkyl, optionally substituted by at least one halogen, or a halogen; or R 1a or R 1a′ and R 1d or R 1d′ form together a bridged carbocyclyl; or R 1a and R 1a′ , R 1b and R 1b′ , R 1c and R 1c′ , or R 1d and R 1d′ forms together a cyclopropyl.
3. The compound according to claim 1 , wherein R 1a ═R 1a′ , R 1b ═R 1b′ , R 1c ═R 1c′ , and R 1d ═R 1d′ .
4. The compound according to claim 1 , wherein two of R 1a , R 1a′ , R 1b , R 1b′ , R 1c , R 1c′ , R 1d , and R 1d′ represent a methyl and the others are a hydrogen.
5. The compound according to claim 1 , wherein at least three of R 1a , R 1a′ , R 1b , R 1b′ , R 1c , R 1c′ , R 1d , and R 1d′ represent a methyl and the others are a hydrogen.
6. The compound according to claim 1 , wherein R 1b and R 1b′ form together a cycloalkyl, and R 1a , R 1a′ , R 1c , R 1c′ , R 1d , and R 1d′ are a hydrogen.
7. The compound according to claim 1 , wherein R 3 is a phenyl, a pyridinyl, a pyridazinyl, a pyrimidinyl, a pyrazinyl, an imidazolyl, or a pyrazolyl, optionally substituted by at least one radical selected from the group consisting of:
a halogen,
a (C 1 -C 6 )alkyl optionally substituted by at least one halogen, or a (C 1 -C 6 )alkyloxy,
a —NH—(C 1 -C 6 )alkyl or a —N—((C 1 -C 6 )alkyl) 2 , optionally substituted by a heterocycloalkyl or a (C 1 -C 6 )alkyloxy,
a —NH-heterocycloalkyl, a —NH-cycloalkyl, a —N((C 1 -C 6 )alkyl)-heterocycloalkyl or a —N((C 1 -C 6 )alkyl)-cycloalkyl, optionally substituted by a (C 1 -C 6 )alkyloxy or a —CO—R 4 with R 4 being a hydrogen or a (C 1 -C 6 )alkyl,
a hydroxy,
a (C 1 -C 6 )alkyloxy optionally substituted by at least one radical selected from the group consisting of a halogen, a hydroxy, a (C 1 -C 6 )alkyloxy, a —NR 5 R 6 with R 5 and R 6 are independently a hydrogen or a (C 1 -C 6 )alkyl, a —NHCOR 7 , a —NHCO 2 R 7 , with R 7 being a (C 1 -C 6 )alkyl, a —CO 2 R 4 with R 4 being a hydrogen or a (C 1 -C 6 )alkyl, and a heterocycle,
a —NHCOR 7 or —NHCO 2 R 7 with R 7 being a (C 1 -C 6 )alkyl, and
a heterocycloalkyl, a heterocycloalkyloxy or a spiroheterocycloalkyl, optionally substituted by a (C 1 -C 6 )alkyloxy, a hydroxy, a halogen or a (C 1 -C 6 )alkyl optionally substituted by a (C 1 -C 6 )alkyloxy.
8. The compound according to claim 1 , wherein R 3 represents a phenyl optionally substituted by at least one radical selected from the group consisting of:
a halogen;
a (C 1 -C 6 )alkyl optionally substituted by at least one halogen,
a —NH—(C 1 -C 6 )alkyl, or a —N—((C 1 -C 6 )alkyl) 2 , optionally substituted by a (C 1 -C 6 )alkyloxy, or a heterocycloalkyl selected from the group consisting of a tetrahydropyranyl, a tetrahydrofuranyl, an oxetanyl, a piperidinyl, and an azetidinyl, said heterocycloalkyl being optionally substituted by a (C 1 -C 6 )alkyloxy or a —CO—R 4 with R 4 being a hydrogen or a (C 1 -C 6 )alkyl,
a —NH-heterocycloalkyl, a —NH-cycloalkyl, a —N((C 1 -C 6 )alkyl)-heterocycloalkyl, or a —N((C 1 -C 6 )alkyl)-cycloalkyl, a —NH-tetrahydropyranyl, a —N(CH 3 )-tetrahydropyranyl, a —NH-tetrahydrofuranyl, a NH-piperidinyl, a —NH-azetidinyl, a —NH-oxetanyl, a-NH-cyclohexyl, or a —N(CH 3 )-cyclobutyl, said —NH-heterocycloalkyl, —NH-cycloalkyl, —N((C 1 -C 6 )alkyl)-heterocycloalkyl, or —N((C 1 -C 6 )alkyl)-cycloalkyl being optionally substituted by a (C 1 -C 6 )alkyloxy or a —CO—R 4 with R 4 being a hydrogen or a (C 1 -C 6 )alkyl,
a (C 1 -C 6 )alkyloxy optionally substituted by at least one radical selected from the group consisting of a halogen, a (C 1 -C 6 )alkyloxy, and a heterocycle, and
a heterocycloalkyl or a spiroheterocycloalkyl, said heterocycloalkyl and spiroheterocycloalkyl are optionally substituted by a (C 1 -C 6 )alkyloxy, a hydroxy, a halogen or a (C 1 -C 6 )alkyl optionally substituted by a (C 1 -C 6 )alkyloxy, and
a heterocycloalkyloxy.
9. The compound according to claim 1 , wherein R 3 represents a pyridinyl, a pyridazinyl, a pyrimidinyl, a pyrazolyl, an imidazolyl, or a pyrazinyl, optionally substituted by at least one radical selected from the group consisting of:
a (C 1 -C 6 )alkyl optionally substituted by at least one halogen,
a (C 1 -C 6 )alkyloxy optionally substituted by at least one halogen,
a heterocycloalkyl, and
a heterocycloalkyloxy.
10. The compound according to claim 1 , wherein said compound is selected from the group consisting of:
11. A pharmaceutical composition comprising a compound as defined in claim 1 and an acceptable pharmaceutical excipient.
12. A pharmaceutical composition comprising a compound as defined in claim 10 and an acceptable pharmaceutical excipient.