US 2004/0072871 A1 · Novel thiophene derivatives, their process of preparation and the pharmaceutical compositions which comprise them

1- Compounds of formula (I):

261
in which:
X represents an oxygen atom or a sulphur atom,
Y represents an oxygen atom, an —NH— group or an —N(C1-C6)alkyl- group,
Ra represents a group selected from hydrogen, halogen, (C1-C3)alkyl, hydroxyl and (C1-C3)alkoxy,
Rb represents a group selected from hydrogen, halogen and (C1-C3)alkyl,
A represents a group selected from phenyl, pyridyl, (C5-C6)cycloalkyl and (C5-C6)cycloalkenyl,
R1 and R2, which are identical or different, each represent, independently of each other, a group selected from:
hydrogen, halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl,
—OR4, —NR4R5, —S(O)R4, —C(O)R4, —CO2R4, —O—C(O)R4, —C(O)NR4R5, —NR5—C(O)R4, —NR5—SO2R4, -T-CN, -T-OR4, -T-OCF3, -T-NR4R5, -T-S(O)nR4, -T- C(O)R4, -T-CO2R4, -T-O—C(O)R4, -T-C(O)NR4R5, -T-NR5—C(O)R4, -T-NR5—SO2R4, —R6 and -T-R6, in which:
n represents an integer from 0 to 2 inclusive,
T represents a linear or branched (C1-C6)alkylene chain optionally substituted by one group selected from oxo, halogen, (C1-C6)alkoxy, hydroxyl, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino and/or in which optionally one of the carbon atoms is replaced by an oxygen atom, a sulphur atom, an —NH— group or an —N(C1-C6)alkyl- group (it being understood that, in the case where one of the carbon atoms is replaced by a group as defined above, then the said alkylene chain comprises at least one sequence of two atoms)
R4 represents a hydrogen atom, a (C1-C6)alkyl, aryl, cycloalkyl group or a heterocycle,
R5 represents a hydrogen atom or a (C1-C6)alkyl group,
R6 represents a group selected from aryl, cycloalkyl and a heterocycle, each of these groups optionally being substituted from one to five identical or different groups selected, independently of each other, from halogen, cyano, nitro, oxo, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkenyl, —OR40, —NR40R50, —S(O)n1R40, —C(O)R40, —CO2R40, —O—C(O)R40, —C(O)NR40R50, —NR50—C(O)R40, —NR50—SO2R40, -T1-CN, -T1-OR40, -T1-OCF3, -T1-NR40R50, -T1-S(O)nR40, -T1-C(O)R40, -T1-CO2R40, -T1-O—C(O)R40, -T1-C(O)NR40 R50, -T1-NR50—C(O)R40, -T1-NR50—SO2R40, -G1 and -T1-G1, in which:
R40, R50, T1 and n1 respectively have the same meanings as R4, R5, T and n as defined above,
G1 represents a group selected from aryl, cycloalkyl and a heterocycle, each of these groups optionally being substituted by 1 to 5 identical or different groups selected, independently of each other, from halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, hydroxyl, (C1-C6)alkoxy, phenoxy, benzyloxy, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, mercapto, (C1-C6)alkylthio, (C1-C7)acyl, (C1-C6)alkylsulphinyl, carboxyl, (C1-C6)alkoxycarbonyl, phenyl and a heterocycle,
R3 represents an —R7 or —U—R11 group, in which:
R7 represents a group selected from hydrogen, (C1-C6)alkyl, aryl, cycloalkyl and heterocycle, each cyclic system optionally being substituted by one to five identical or different groups selected, independently of each other, from halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, —OR8, —NR8R9, —S(O)mR8, —C(O)R8, —CO2R8, —O—C(O)R8, —C(O)NR8R9, —NR9—C(O)R8, —NR9—SO2R8, —V—CN, —V—OR8, —V—NR8R9, —V—S(O)mR8, —V—C(O)R8, —V—CO2R8, —V—O—C(O)R8, —V—C(O)NR8R9, —V—NR9—C(O)R8, —V—NR9—SO2R8, —R10 and —V—R10, in which:
m represents an integer from 0 to 2 inclusive,
V represents a group selected from a linear or branched (C1-C6)alkylene chain, a linear or branched (C2-C6)alkenylene chain, a cyclopropylene group and a linear or branched (C2-C6)alkylene chain in which one of the carbon atoms is replaced by an oxygen agom, a sulphur atom, an —NH— group or an —N(C1-C6)alkyl- group,
R8 represents a hydrogen atom, a (C1-C6)alkyl, aryl or cycloalkyl group or a heterocycle,
R9 represents a hydrogen atom or a (C1-C6)alkyl group,
R10 represents an aryl or cycloalkyl group or a heterocycle,
U represents a linear or branched (C1-C6)alkylene chain optionally substituted by one hydroxyl group or a linear or branched (C2-C6)alkylene chain in which one of the carbon atoms is replaced by an oxygen atom, a sulphur atom, an —NH— group or an —N(C1-C6)alkyl- group,
R11 represents a group selected from halogen, —OR12, —NR12R13, —S(O)pR12, —C(O)R12, —CO2R12, —O—C(O)R12, —C(O)NR12R13, —NR13—C(O)R12, —NR13—SO2R12 and —R14, the latter group optionally being substituted by one to three identical or different groups selected, independently of each other, from halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —OR15, —NR15R16, —S(O)qR15, —C(O)R15, —O—C(O)R15, —CO2R15, —C(O)NR15R16, —NR16—C(O)R15, —NR16—SO2R15, —R17, —W—CN, —W—OR15, —W—NR15R16, —W—S(O)qR15, —W—C(O)R15, —W—CO2R15, —W—O—C(O)R15, —W—C(O)NR15R16, —W—NR16—C(O)R15, —W—NR16—SO2R15, —W—R17 and —C(O)—W1—CO2R15, in which:
R12 represents a hydrogen atom, a (C1-C6)alkyl, aryl, cycloalkyl group or a heterocycle,
R13 represents a hydrogen atom or a (C1-C6)alkyl group,
R14 represents an aryl or cycloalkyl group or a heterocycle,
R15 represents a hydrogen atom, a (C1-C6)alkyl, aryl or cycloalkyl group or a heterocycle,
R16 represents a hydrogen atom or a (C1-C6)alkyl group,
R17 represents an aryl or cycloalkyl group or a heterocycle,
p represents an integer from 0 to 2 inclusive,
q represents an integer from 0 to 2 inclusive,
W represents a group selected from a linear or branched (C1-C6)alkylene chain, a linear or branched (C2-C6)alkenylene chain, a cyclopropylene group and a linear or branched (C2-C6)alkylene chain in which one of the carbon atoms is replaced by an oxygen atom, a sulphur atom, an —NH— group or an —N(C1-C6)alkyl- group,
W1 represents a linear or branched (C1-C6)alkylene chain,
their isomers, and their addition salts with a pharmaceutically acceptable acid or base, it being understood that:
the term “aryl group” denotes a monocyclic or bicyclic aromatic system comprising from 4 to 10 carbon atoms, it being understood that, in the case of a bicyclic system, one of the rings exhibits an aromatic nature and the other ring is aromatic or unsaturated,
the term “cycloalkyl group” denotes a saturated or partially unsaturated, fused or bridged, bicyclic or monocyclic system comprising from 3 to 12 carbon atoms,
the term “a heterocycle” denotes a saturated, unsaturated or aromatic, 3- to 12-membered, fused or bridged, bicyclic or monocyclic system comprising from 1 to 4 identical or different heteroatoms selected, independently of each other, from oxygen, sulphur and nitrogen and optionally comprising 1 or 2 oxo or thioxo groups, it being understood that, in the case of a bicyclic system, one of the rings exhibits an aromatic nature and the other ring is aromatic or unsaturated, or both rings are saturated, or one of the rings is saturated and the other ring is unsaturated, or both rings are unsaturated,
the term “(C1-C6)alkyl group” denotes a linear or branched carbonaceous chain comprising from 1 to 6 carbon atoms,
the term “halo(C1-C6)alkyl group” denotes a linear or branched carbonaceous chain comprising from 1 to 6 carbon atoms and substituted by 1 to 6 halogen atoms,
the term “halo(C1-C6)alkoxy group” denotes a linear or branched carbonaceous chain comprising from 1 to 6 carbon atoms and substituted by 1 to 6 halogen atoms, the said chain being connected to the compound of formula (I) by an oxygen atom,
the term “halogen atom” denotes an atom selected from bromine, chlorine, fluorine and iodine,
the term “acyl group” denotes a hydrogen atom, an alkyl group as defined above, a cycloalkyl comprising 3 to 6 carbon atoms or a phenyl group bonded through an oxo group to the compounds of formula (I),
it also being understood that the compounds of formula (I) are not:
ethyl 5-methyl-4-phenylthiophen-2-ylcarboxylate,
5-methyl-4-phenylthiophen-2-ylcarboxylic acid,
methyl 3-hydroxy-4-phenylthiophen-2-ylcarboxylate,
methyl 3-methoxy-4-phenylthiophen-2-ylcarboxylate,
3-methoxy-4-phenylthiophen-2-ylcarboxylic acid,
methyl 4-(4-methoxyphenyl)thiophen-2-ylcarboxylate,
methyl 4-phenylthiophen-2-ylcarboxylate,
4-(4-methoxyphenyl)thiophen-2-ylcarboxylic acid,
4-phenylthiophen-2-ylcarboxylic acid,
4-(4-tert-butylphenyl)thiophen-2-ylcarboxylic acid,
methyl 5-chloro-3-hydroxy-4-phenylthiophen-2-ylcarboxylate,
4-(3,5-dimethylphenyl)thiophen-2-ylcarboxylic acid,
methyl 4-[4-(acetylamino)phenyl]thiophen-2-ylcarboxylate,
ethyl 4-phenylthiophen-2-ylcarboxylate,
4-phenylthiophen-2-ylcarboxamide,
N-methyl-4-phenylthiophen-2-ylcarboxamide,
N,N-dimethyl-4-phenylthiophen-2-ylcarboxamide,
5-methyl-4-phenylthiophen-2-ylcarboxamide,
N-methyl-5-methyl-4-phenylthiophen-2-ylcarboxamide,
N,N-dimethyl-5-methyl-4-phenylthiophen-2-ylcarboxamide,
methyl 2-{[4-(4-methoxyphenyl)thiophen-2-yl]carboxamido}benzoate,
N-[3-(trifluoromethyl)phenyl]-4-(4-methoxyphenyl)thiophen-2-ylcarboxamide,
methyl 4-(2-bromophenyl)thiophen-2-ylcarboxylate,
methyl 4-(3-bromophenyl)thiophen-2-ylcarboxylate,
methyl 4-(4-bromophenyl)thiophen-2-ylcarboxylate,
N-(2-methoxyethyl)-4-(4-methoxyphenyl)thiophen-2-ylcarboxamide,
N-isopropyl-4-(4-methoxyphenyl)thiophen-2-ylcarboxamide,
4-(4-methoxyphenyl)-N-(2-morpholinoethyl)thiophen-2-ylcarboxamide,
4-(4-chlorophenyl)-N-(2-methoxyethyl)thiophen-2-ylcarboxamide,
4-(4-chlorophenyl)-N-(2-morpholinoethyl)thiophen-2-ylcarboxamide,
4-(4-chlorophenyl)-N-(2-phenylethyl)thiophen-2-ylcarboxamide,
4-(4-chlorophenyl)-N-(tetrahydrofurylmethyl)thiophen-2-ylcarboxamide,
and 4-(4-methoxyphenyl)-N-(tetrahydrofurylmethyl)thiophen-2-ylcarboxamide;
it also being understood that:
if Ra represents a hydrogen atom, A represents a cyclopenten-1-yl group substituted in the 2 position by an R1 group taking the definition thienyl optionally substituted, then Rb represents a group selected from hydrogen, halogen and (C2-C3)alkyl,
if R3 represents an R7 group taking the definition heterocycle, then the said heterocycle cannot represent a 1-azabicyclo[2.2.2]oct-3-yl group,
and if R3 represents an R7 group taking the definition phenyl substituted in the para position by an R10 group, then the said Rio group cannot represent a 5-methyl-4,5-dihydro-3-oxo-2H-pyridazin-6-yl group.

80 more elements

2- Compounds of formula (I) according to claim 1, in which:

X represents an oxygen atom or a sulphur atom,
Y represents an oxygen atom, an —NH— group or an —N(C1-C6)alkyl- group,
Ra represents a group selected from hydrogen, halogen, (C1-C3)alkyl, hydroxyl and (C1-C3)alkoxy,
Rb represents a group selected from hydrogen, halogen and (C1-C3)alkyl,
A represents a group selected from phenyl, (C5-C6)cycloalkyl and (C5-C6)cycloalkenyl,
R1 and R2, which are identical or different, each represent, independently of each other, a group selected from:
hydrogen, halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl,
—OR4, —NR4R5, —S(O)nR4, —C(O)R4, —CO2R4, —O—C(O)R4, —C(O)NR4R5, —NR5—C(O)R4, —NR5—SO2R4, -T-CN, -T-OR4, -T-OCF3, -T-NR4R5, -T-S(O)nR4, -T- C(O)R4, -T-CO2R4, -T-O—C(O)R4, -T-C(O)NR4R5, -T-NR5—C(O)R4, -T-NR5—SO2R4, —R6 and -T-R6, in which:
n represents an integer from 0 to 2 inclusive,
T represents a linear or branched (C1-C6)alkylene chain optionally substituted by a group selected from oxo, halogen, (C1-C6)alkoxy, hydroxyl, amino, mono(C1-C6)alkylamino and di(C1-C6)alkylamino and/or in which optionally one of the carbon atoms is replaced by an oxygen atom, a sulphur atom, an —NH— group or an —N(C1-C6)alkyl- group (it being understood that, in the case where one of the carbon atoms is replaced by a group as defined above, then the said alkylene chain comprises at least one sequence of two atoms)
R4 represents a hydrogen atom, a (C1-C6)alkyl, aryl or cycloalkyl group or a heterocycle,
R5 represents a hydrogen atom or a (C1-C6)alkyl group,
R6 represents a group selected from aryl, cycloalkyl and a heterocycle, each of these groups optionally being substituted by one to five identical or different groups selected, independently of each other, from halogen, cyano, nitro, oxo, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkenyl, —OR40, —NR40R50, —S(O)n1R40, —C(O)R40, —CO2R40, —O—C(O)R40, —C(O)NR40R50, —NR50—C(O)R40, —NR50—SO2R40, -T1-CN, -T1-OR40, -T1-OCF3, -T1-NR40R50, -T1-S(O)nR40, -T1-C(O)R40, -T1-CO2R40, -T1-O—C(O)R40, -T1-C(O)NR40R50, -T1-NR50—C(O)R40, -T1-NR50—SO2R40, —G1 and -T1-G1, in which:
R40, R50, T1 and n1 respectively have the same meanings as R4, R5, T and n as defined above,
G1 represents a group selected from aryl, cycloalkyl and a heterocycle, each of these groups optionally being substituted by 1 to 5 identical or different groups selected, independently of each other, from halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, hydroxyl, (C1-C6)alkoxy, phenoxy, benzyloxy, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, mercapto, (C1-C6)alkylthio, (C1-C7)acyl, (C1-C6)alkylsulphinyl, carboxyl, (C1-C6)alkoxycarbonyl, phenyl and a heterocycle,
R3 represents an —R7 or —U—R11 group, in which:
R7 represents a group selected from hydrogen, (C1-C6)alkyl, aryl, cycloalkyl and heterocycle, each cyclic system optionally being substituted by one to five identical or different groups selected, independently of each other, from halogen, cyano, nitro, hato(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, —OR8, —NR8R9, —S(O)mR8, —C(O)R8, —CO2R8, —O—C(O)R8, —C(O)NR8R9, —NR9—C(O)R8, —NR9—SO2R8, —V—CN, —V—OR8, —V—NR8R9, —VS(O)mR8, —V—C(O)R8, —V—CO2R8, —V—O—C(O)R8, —V—C(O)NR8R9, —V—NR9—C(O)R8, —V—NR9—SO2R8, —R10 and —V—R10, in which:
m represents an integer from 0 to 2 inclusive,
V represents a group selected from a linear or branched (C1-C6)alkylene chain, a linear or branched (C2-C6)alkenylene chain, a cyclopropylene group and a linear or branched (C2-C6)alkylene chain in which one of the carbon atoms is replaced by an oxygen agom, a sulphur atom, an —NH— group or an —N(C1-C6)alkyl- group,
R8 represents a hydrogen atom, a (C1-C6)alkyl, aryl or cycloalkyl group or a heterocycle,
R9 represents a hydrogen atom or a (C1-C6)alkyl group,
R10 represents an aryl or cycloalkyl group or a heterocycle,
U represents a linear or branched (C1-C6)alkylene chain optionally substituted by a hydroxyl group or a linear or branched (C2-C6)alkylene chain in which one of the carbon atoms is replaced by an oxygen atom, a sulphur atom, an —NH— group or an —N(C1-C6)alkyl- group,
R11 represents a group selected from halogen, —OR12, —NR12R13, —S(O)pR12, —C(O)R12, —CO2R12, —O—C(O)R12, —C(O)NR12R13, —NR13—C(O)R12, —NR13—SO2R12 and —R14, the latter group optionally being substituted by one to three identical or different groups selected, independently of each other, from halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —OR15, —NR15R16, —S(O)qR15, —C(O)R15, —O—C(O)R15, —CO2R15, —C(O)NR15R16, —NR16—C(O)R15, —NR16—SO2R15, —R17, —W—CN, —W—OR,5, —W—NR15R6, —W—S(O)qR15, —W—C(O)R15, —W—CO2R15, —W—O—C(O)R15, —W—C(O)NR15R16, —W—NR16—C(O)R15, W—NR16—SO2R15, —W—R17 and —C(O)—W1—CO2R15, in which:
R12 represents a hydrogen atom, a (C1-C6)alkyl, aryl or cycloalkyl group or a heterocycle,
R13 represents a hydrogen atom or a (C1-C6)alkyl group,
R14 represents an aryl or cycloalkyl group or a heterocycle,
R15 represents a hydrogen atom, a (C1-C6)alkyl, aryl or cycloalkyl group or a heterocycle,
R16 represents a hydrogen atom or a (C1-C6)alkyl group,
R17 represents an aryl or cycloalkyl group or a heterocycle,
p represents an integer from 0 to 2 inclusive,
q represents an integer from 0 to 2 inclusive,
W represents a group selected from a linear or branched (C1-C6)alkylene chain, a linear or branched (C2-C6)alkenylene chain, a cyclopropylene group and a linear or branched (C2-C6)alkylene chain in which one of the carbon atoms is replaced by an oxygen atom, a sulphur atom, an —NH— group or an —N(C1-C6)alkyl- group,
W1 represents a linear or branched (C1-C6)alkylene chain, their isomers, and their addition salts with a pharmaceutically acceptable acid or base,
it also being understood that the compounds of formula (I) are not:
ethyl 5-methyl-4-phenylthiophen-2-ylcarboxylate,
5-methyl-4-phenylthiophen-2-ylcarboxylic acid,
methyl 3-hydroxy-4-phenylthiophen-2-ylcarboxylate,
methyl 3-methoxy-4-phenylthiophen-2-ylcarboxylate,
3-methoxy-4-phenylthiophen-2-ylcarboxylic acid,
methyl 4-(4-methoxyphenyl)thiophen-2-ylcarboxylate,
methyl 4-phenylthiophen-2-ylcarboxylate,
4-(4-methoxyphenyl)thiophen-2-ylcarboxylic acid,
4-phenylthiophen-2-ylcarboxylic acid,
4-(4-tert-butylphenyl)thiophen-2-ylcarboxylic acid,
methyl 5-chloro-3-hydroxy-4-phenylthiophen-2-ylcarboxylate,
4-(3,5-dimethylphenyl)thiophen-2-ylcarboxylic acid,
methyl 4-[4-(acetylamino)phenyl]thiophen-2-ylcarboxylate,
ethyl 4-phenylthiophen-2-ylcarboxylate,
4-phenylthiophen-2-ylcarboxamide,
N-methyl-4-phenylthiophen-2-ylcarboxamide,
N,N-dimethyl-4-phenylthiophen-2-ylcarboxamide,
5-methyl-4-phenylthiophen-2-ylcarboxamide,
N-methyl-5-methyl-4-phenylthiophen-2-ylcarboxamide,
N,N-dimethyl-5-methyl-4-phenylthiophen-2-ylcarboxamide,
methyl 2-{[4-(4-methoxyphenyl)thiophen-2-yl]carboxamido}benzoate,
N-[3-(trifluoromethyl)phenyl]-4-(4-methoxyphenyl)thiophen-2-ylcarboxamide,
methyl 4-(2-bromophenyl)thiophen-2-ylcarboxylate,
methyl 4-(3-bromophenyl)thiophen-2-ylcarboxylate,
methyl 4-(4-bromophenyl)thiophen-2-ylcarboxylate,
N-(2-methoxyethyl)-4-(4-methoxyphenyl)thiophen-2-ylcarboxamide,
N-isopropyl-4-(4-methoxyphenyl)thiophen-2-ylcarboxamide,
4-(4-methoxyphenyl)-N-(2-morpholinoethyl)thiophen-2-ylcarboxamide,
4-(4-chlorophenyl)-N-(2-methoxyethyl)thiophen-2-ylcarboxamide,
4-(4-chlorophenyl)-N-(2-morpholinoethyl)thiophen-2-ylcarboxamide,
4-(4-chlorophenyl)-N-(2-phenylethyl)thiophen-2-ylcarboxamide,
4-(4-chlorophenyl)-N-(tetrahydrofurylmethyl)thiophen-2-ylcarboxamide,
and 4-(4-methoxyphenyl)-N-(tetrahydrofurylmethyl)thiophen-2-ylcarboxamide;
it also being understood that:
if Ra represents a hydrogen atom, A represents a cyclopenten-1-yl group substituted in the 2 position by an R1 group taking the definition thienyl optionally substituted, then Rb represents a group selected from hydrogen, halogen and (C2-C3)alkyl,
if R3 represents an R7 group taking the definition heterocycle, then the said heterocycle cannot represent a 1-azabicyclo[2.2.2]oct-3-yl group,
and if R3 represents an R7 group taking the definition phenyl substituted in the para position by an R10 group, then the said R10 group cannot represent a 5-methyl-4,5-dihydro-3-oxo-2H-pyridazin-6-yl group.

69 more elements

14- Compounds of formula (I) according to claim 1, which are:

4-(4-Isopropylphenyl)-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-(4-Biphenyl)-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-(4-Ethylphenyl)-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(Methylthio)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(Trifluoromethoxy)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(tert-Butyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(Trifluoromethyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-(4-Hydroxyphenyl)-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(Pyridin-4-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
Methyl 4′-[5-(2-morpholin-4-ylethylcarbamoyl)thiophen-3-yl]biphenyl-3-carboxylate
4-[4-(Pyridin-3-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(Morpholin-4-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-(4-Piperidinophenyl)-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(Pyrrolidin-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-( 1,4-Dioxa-8-azaspiro[4,5]dec-8-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(1,2,3,6-Tetrahydropyridin-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(3-(3R)-Hydroxypyrrolidin-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(1H-Imidazol-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
N-(2-Morpholin-4-ylethyl)-4-[4-(1H-pyrrol-1-yl)phenyl]thiophene-2-carboxamide
4-[4-(Isoxazol-5-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(Cyclohexyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(1-Methyl-1H-pyrazol-3-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
4-[4-(6-Oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide
Methyl trans-4-{[4-(4-phenylcyclohex-1-enyl)thiophene-2-carboxamido]methyl}-cyclohexanecarboxylate
trans 4-{[4-(4-Phenylcyclohex-1-enyl)thiophene-2-carboxamido]methyl}cyclohexane-carboxylic acid
Ethyl 3-(6-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}pyridin-3-yl)-propanoate
3-(6-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}pyridin-3-yl)propanoic acid
Ethyl 3-(4-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}phenyl)propenoate
3-(4-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}phenyl)propenoic acid
Diethyl 4-({[4-(trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phthalate
4-({[4-(Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phthalic diacid
Ethyl 3-(4-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}phenyl)propanoate
3-(4-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}phenyl)propanoic acid
Methyl trans-4-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)-cyclohexanecarboxylate
trans-4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)cyclohexane-carboxylic acid
Ethyl 2-[4-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetate
2-[4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid
Ethyl 3-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)benzoate
3-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)benzoic acid
Ethyl 2-[3-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetate
2-[3-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid
Ethyl 4-′{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)cyclohexane-carboxylate
4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)cyclohexane carboxylic acid
Methyl 6-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)nicotinate
6-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)nicotinic acid
Ethyl 4-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)benzoate
4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)benzoic acid
Ethyl 4-({[4-(4-methylthiophenyl)thien-2-yl]carboxamido}methyl)benzoate
4-({[4-(4-Methylthiophenyl)thien-2-yl]carboxamido}methyl)benzoic acid
Ethyl 4-({[4-(4-(tert-butyl)phenyl)thien-2-yl]carboxamido}methyl)benzoate
4-({[4-(4-(tert-Butyl)phenyl)thien-2-yl]carboxamido}methyl)benzoic acid
Ethyl (4-{[4-(4-(tert-butyl)phenyl)thien-2-yl]carboxamido}phenyl)acetate
(4-{[4-(4-(tert-Butyl)phenyl)thien-2-yl]carboxamido}phenyl)acetic acid
Ethyl (4-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}phenyl)acetate
(4-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}phenyl)acetic acid
Ethyl (4-{[4-(4-methylthiophenyl)thien-2-yl]carboxamido}phenyl)acetate
(4-{[4-(4-Methylthiophenyl)thien-2-yl]carboxamido}phenyl)acetic acid
Ethyl 4-({[4-(4-methoxyphenyl)thien-2-yl]carboxamido}methyl)benzoate
4-({[4-(4-Methoxyphenyl)thien-2-yl]carboxamido}methyl)benzoic acid
Ethyl (4-{[4-(4-methoxyphenyl)thien-2-yl]carboxamido}phenyl)acetate
(4-{[4-(4-Methoxyphenyl)thien-2-yl]carboxamido}phenyl)acetic acid
Ethyl 3-[4-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]-propanoate
3-[4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]propanoic acid
Ethyl 3-[3-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido }methyl)phenyl]-propanoate
3-[3-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]propanoic acid
Ethyl 7-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}heptanoate
7-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}heptanoic acid
Ethyl 4-({[4-(4-hydroxyphenyl)thien-2-yl]carboxamido}methyl)cyclohexanecarboxylate
Ethyl 4-[({4-[4-(pyridin-4-yl)phenyl]thien-2-yl}carboxamido)methyl]cyclohexane-carboxylate
4-[({4-[4-(Pyridin-4-yl)phenyl]thien-2-yl]carboxamido)methyl]cyclohexanecarboxylic acid hydrochloride
4-(4-Bromophenyl)-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(4-Acetylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(4-Fluorophenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(3-Hydroxyphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(4-Methylsulphonylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(3-Acetylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
N-(2-Morpholin-4-ylethyl)-4-[4-(trifluoromethoxy)phenyl]thiophene-2-carbothioamide,
N-(2-Morpholin-4-ylethyl)-4-[4-(1,2,3-thiadiazol-4-yl)phenyl]thiophene-2-carboxamide,
4-(4-Isoxazol-5-ylphenyl)-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
trans-[4-([4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido)cyclohexyl]acetic acid,
2-[4-({[4-(4-Phenoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
4-(4-Trifluoromethoxyphenyl)-N-methylthiophene-2-carboxamide,
2-[4-({[4-(4-Benzyloxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
N-(3,5-Difluoro-4-hydroxybenzyl)-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
4-[4-(3-Nitrophenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(2-Chlorophenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(3-Cyanophenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(2-Formylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(3,4,5-Trimethoxyphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-{4-[4-(Hydroxymethyl)phenyl]phenyl}-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(3-Acetamidophenyl)phenyl-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-{4-[3,4-(Methylenedioxy)phenyl]phenyl}-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
N-(Cyclopropylmethyl)-4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide,
N-(tert-Butyl)-4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide,
N-(Cyclopropyl)-4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide,
N-(Cyclopentyl)-4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide,
N-(2-Hydroxyethyl)-4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide,
N-(Cyclopentylmethyl)-4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide,
trans-4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}-methyl)cyclohexanecarboxylic acid, sodium salt
4-{4-[(3-Chloro-4-fluoro)phenyl]phenyl}-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-{4-[3-(Hydroxymethyl)phenyl]phenyl}-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
Ethyl 2-[4-({[4-(4′-propionyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetate
2-[4-({[4-(4′-Propionyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
Ethyl 2-[4-({[4-(4′-cyclopropylcarbonyl-4-biphenyl)thien-2-yl]carboxamido}methyl) phenyl acetate,
2-[4-({[4-(4′-Cyclopropylcarbonyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]-acetic acid,
Ethyl 2-[4-({[4-(4′-benzoyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetate,
2-[4-({[4-(4′-Benzoyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
Ethyl 2-[4-({[4-(4′-cyanomethyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetate,
2-[4-({[4-(4′-Cyanomethyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
Ethyl 2-{4-[({4-[4-(pyrimidin-5-yl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}acetate,
2-{4-[({4-[4-(Pyrimidin-5-yl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}acetate acid,
Ethyl 2-{4-[({4-[4-(4-acetyl-3-hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}acetate,
2-{4-[({4-[4-(4-Acetyl-3-hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}-acetic acid,
Ethyl 2-{4-[({4-[4-(2-hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}acetate,
2-{4-[({4-[4-(2-Hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}acetic acid,
Ethyl 2-{4-[({4-[4-(4-acetyl-2-methoxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}acetate,
2-{4-[({4-[4-(4-Acetyl-2-hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}-acetic acid,
Ethyl 2-{4-[({4-[4-(4-(2-oxopropyl)-3-hydroxyphenyl)phenyl]thien-2-yl}carboxamido) methyl]phenyl}acetate,
2-{4-[({4-[4-(4-(2-Oxopropyl)-3-hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]-phenyl}acetic acid,
4-[4-(2-Fluorophenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
N-[2-(Hydroxymethyl)cyclohexyl]-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
Ethyl trans-4-[({4-[4-(4-acetylphenyl)phenyl]thien-2-yl}carboxamido)methyl]cyclohexanecarboxylate,
trans-4-[({4-[4-(4-Acetylphenyl)phenyl]thien-2-yl}carboxamido)methyl]cyclohexane-carboxylic acid,
Methyl trans-3-(3-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}cyclohexyl) propanoate,
trans-3-(3-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}cyclohexyl)propanoic acid,
Methyl trans-(3-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}cyclohexyl) acetate,
trans-(3-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}cyclohexyl)acetic acid,
Methyl trans-3-(4-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}cyclohexyl) propanoate,
trans-3-(4-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}cyclohexyl)propanoic acid,
Methyl [4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)cyclohexyl]acetate,
[4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)cyclohexyl]acetic acid,
Ethyl 2-hydroxy-5-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl) benzoate,
2-Hydroxy-5-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)benzoic acid,
Methyl 6-({[4-(4′-acetyl-4-biphenyl)thien-2-yl]carboxamido}methyl)nicotinate,
6-({[4-(4′-Acetyl-4-biphenyl)thien-2-yl]carboxamido}methyl)nicotinic acid,
N-(Pyridin-4-yl)-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
N-(2-Hydroxy-1-hydroxymethyl-1-methylethyl)-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
N-(2-Hydroxypropyl)-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
N-(2-Hydroxy-1,1-dimethylethyl)-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
4-(4-Trifluoromethoxyphenyl)-N-(tetrahydrofuran-2-ylmethyl)thiophene-2-carboxamide,
N-(2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
Ethyl 3-[4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamido]butyrate,
3-[4-(4-Trifluoromethoxyphenyl)thiophene-2-carboxamido]butyric acid,
N-[3-(Methylsulphinyl)propyl]-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
N-(2-Morpholin-4-ylethyl)-4-[4-(2,2,2-trifluoroethoxy)phenyl]thiophene-2-carboxamide,
{4′-[5-(2-Morpholin-4-ylethylcarbamoyl)thiophen-3-yl]biphenyl-4-yl}acetic acid, sodium salt,
Ethyl trans-4-({[4-[4-(trifluoromethoxy)phenyl]thien-2-yl]carbothioamido}methyl)-cyclohexanecarboxylate,
trans-4-({[4-[4-(trifluoromethoxy)phenyl]thien-2-yl]carbothioamido}methyl)-cyclohexane carboxylic acid,
Ethyl (2S)-2-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}-3-methylbutanoate,
(2S)-2-{[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}-3-methylbutanoic acide,
and N-(2-Morpholin-4-ylethyl)-4-(5-phenylpyridin-2-yl)thiophen-2-carboxamide.

148 more elements

15- Compounds of formula (I) according to claim 1, which are:

4-(4-Biphenyl)-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(Pyridin-4-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(Pyridin-3-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(Pyrrolidin-1-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(Cyclohexyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(1-Methyl-1H-pyrazol-3-yl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
3-(6-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamidopyridin-3-yl)propanoic acid,
3-(4-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}phenyl)propanoic acid,
trans-4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)cyclohexane-carboxylic acid,
2-[4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido[methyl)phenyl]acetic acid,
2-[3-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido{methyl)phenyl]acetic acid,
4-{[4-(4-Trifluoromethoxyphenyl)thiophene-2-carboxamido]methyl}cyclohexane-carboxylic acid,
6-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)nicotinic acid,
4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)benzoic acid,
(4-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}phenyl)acetic acid,
3-[4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]-propanoic acid,
3-[3-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]-propanoic acid,
4-[({4-[4-(Pyridin-4-yl)phenyl]thien-2-yl}carboxamido)methyl]cyclohexanecarboxylic acid hydrochloride,
4-[4-(4-Acetylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(4-Fluorophenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(3-Hydroxyphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(4-Methylsulphonylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
4-[4-(3-Acetylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
2-[4-({[4-(4-phenoxyphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
N-(3,5-Difluoro-4-hydroxybenzyl)-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
4-[4-(4-Hydroxymethylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
trans-4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}-methyl)cyclohexanecarboxylic acid, sodium salt
4-[4-(3-Hydroxymethylphenyl)phenyl]-N-(2-morpholin-4-ylethyl)thiophene-2-carboxamide,
2-[4-({[4-(4′-Propionyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
2-[4-({[4-(4′-Cyclopropylcarbonyl-4-biphenyl)thien-2-yl]carboxamido}methyl)-phenyl]acetic acid,
2-[4-({[4-(4′-Benzoyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
2-[4-({[4-(4 ′-Cyanomethyl-4-biphenyl)thien-2-yl]carboxamido}methyl)phenyl]acetic acid,
2-{4-[({4-[4-(Pyrimidin-5-yl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}acetic acid,
2-{4-[({4-[4-(4-Acetyl-3-hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]-phenyl}acetic acid,
2-{4-[({4-[4-(2-Hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]phenyl}acetic acid,
2-{4-[({4-[4-(4-Acetyl-2-hydroxyphenyl)phenyl]thien-2-yl}carboxamido)methyl]-phenyl}acetic acid,
N-[2-(Hydroxymethyl)cyclohexyl]-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide,
trans-4-[({4-[4-(4-Acetylphenyl)phenyl]thien-2-yl}carboxamido)methyl]cyclohexane-carboxylic acid,
trans-3-(3-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}cyclohexyl)-propanoic acid,
trans-3-(4-{[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}cyclohexyl)-propanoic acid,
[4-({[4-(4-Trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)cyclohexyl]acetic acid,
2-Hydroxy-5-({[4-(4-trifluoromethoxyphenyl)thien-2-yl]carboxamido}methyl)benzoic acid,
6-({[4-(4′-Acetyl-4-biphenyl)thien-2-yl]carboxamido}methyl)nicotinic acid,
and N-(Pyridin-4-yl)-4-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide.

41 more elements

17- Process for the preparation of the compounds of formula (I), characterized in that use is made, as starting material, of a compound of formula (II):

263
in which Ra and Rb are as defined in the formula (I) and P1 represents a halogen atom or a triflate group,
which compounds of formula (II) are subjected to oxidation conditions in the presence, for example, of silver nitrate in a basic medium, to give the compounds of formula (III):
264
in which Ra, Rb and P1 are as defined above,
which compounds of formula (III) are optionally converted to the corresponding acid chlorides (IV) by reaction with oxalyl chloride, for example,
265
in which Ra, Rb and P1 are as defined above,
or which compounds of formula (III) are treated directly, under peptide coupling conditions in the presence of a coupling agent and in a basic and polar medium, with a compound of formula (V):
HY—R3 (V)
in which Y and R3 have the same meanings as in the compounds of formula (I), to yield to the compounds of formula (VI):
266
in which Ra, Rb, R3, Y and P1 are as defined above,
which compounds of formula (VI) are:
either reacted, under basic palladium coupling conditions, with a compound of formula (VII):
267
in which A, R1 and R2 have the same meanings as in the compounds of formula (I), to yield to the compounds of formula (I/a), a particular case of the compounds of formula (I):
268
in which Ra, Rb, R1, R2, R3, Y and A are as defined above,
or treated with hexamethylditin, in the presence of a palladium catalyst, to yield to the compounds of formula (VIII):
269
in which Ra, Rb, R3 and Y are as defined above,
which componds of formula (VIII) are reacted:
with a compound of formula (IX):
270
in which R1, R2 and A have the same meanings as in the formula (I) and G10 represents a halogen atom selected from chlorine and bromine or a triflate group,
either in the presence of triphenylphosphinearsenic and of a palladium catalyst, in the case where G10 represents a triflate group,
or in the presence of a cupric halide compound, such as CuBr2, and of a palladium catalyst, under polar solvent conditions, in the case where G10 represents a halogen atom,
to also yield to the compounds of formula (I/a) as described above,
or treated with bis(pinacolato)diborane, followed by an oxidation reaction, to yield to the compounds of formula (VIa):
271
in which Ra, Rb, R3 and Y are as defined above,
which compounds of formula (VIa) are reacted, under basic palladium coupling conditions, with a compound of the formula (IX):
272
in which A, R1, R2 and G10 are as defined above,
to also yield to the compounds of formula (I/a) as defined above:
273
in which Ra, Rb, R1, R2, R3, Y and A are as defined above,
or reacted with a compound of formula (IXa):
274
in which A, R1, and R2 are as defined in the formula (I),
either in the presence of triphenylphosphinearsenic and of a palladium catalyst, in the case where PI in the compounds of formula (VI) represents a triflate group,
or in the presence of a cupric halide compound, such as CuBr2, and of a palladium catalyst, under polar solvent conditions, in the case where P1 in the compounds of formula (VI) represents a halogen atom,
to also yield to the compounds of formula (I/a) as described above,
275
in which Ra, Rb, R1, R2, R3, Y and A are as defined above,
which compounds of formula (I/a), in the specific case where they represent compounds of formula (I/b), in which A represents a phenyl group, R2 represents a hydrogen atom, R1 represents a hydroxyl group or a halogen atom (Hal) and Ra, Rb, Y and R3 have the same meanings as in the formula (I):
276
can then be treated beforehand with trifluoromethanesulphonic anhydride in the presence of a strong base, in the case where R1 represents a hydroxyl group, to produce the triflate activated derivative,
it then being possible for the said compounds carrying an R1 group taking the definition halogen or triflate:
either to be reacted under basic conditions and in the presence of a palladium catalyst with a compound of formula (X):
277
in which R6 is as defined in the formula (I), that is to say that it represents a group selected from aryl and cycloalkyl and a heterocycle, each optionally being substituted,
to yield to the compounds of formula (I/c), a particular case of the compounds of formula (I):
278
in which R6, Ra, Rb, Y and R3 are as defined above,
or to be treated with bis(pinacolato)diborane, followed by an oxidation reaction, to yield to the compounds of formula (XI):
279
in which Ra, Rb, Y and R3 are as defined above,
which compounds of formula (XI) are reacted under basic conditions and in the presence of a palladium catalyst with a compound of formula (Xa):
R6—P2 (Xa)
in which R6 is as defined in the formula (I), that is to say that it represents a group selected from aryl and cycloalkyl and a heterocycle, each optionally being substituted, and P2 represents a halogen atom or a triflate group,
to also yield to the compounds of formula (I/c) as defined above:
280
in which R6, Ra, Rb, Y and R3 are as defined above,
or to be treated with hexamethylditin in the presence of a palladium catalyst, to yield to the compounds of formula (XIa):
281
in which Ra, Rb, R3 and Y are as defined above,
which compounds of formula (XIa) are reacted with a compound of formula (Xa) as defined above:
R6—P2 (Xa)
in which R6 is as defined in the formula (I) and P2 represents a halogen atom or a triflate group,
either in the presence of triphenylphosphinearsenic and of a palladium catalyst, in the case where P2 represents a triflate group,
or in the presence of a cupric halide compound, such as CuBr2, and of a palladium catalyst, under polar solvent conditions, in the case where P2 represents a halogen atom,
to also yield to the compounds of formula (I/c) as defined above:
282
in which R6, Ra, Rb, Y and R3 are as defined above,
or to be reacted with a compound of formula (Xb):
R6—SnMe3 (Xb)
in which R6 is as defined above,
either in the presence of triphenylphosphinearsenic and of a palladium catalyst, in the case where the compounds of formula (I/b) comprise a triflate group,
or in the presence of a cupric halide compound, such as CuBr2, and of a palladium catalyst, under polar solvent conditions, in the case where the compounds of formula (I/b) comprise a halogen atom,
to also yield to the compounds of formula (I/c) as described above,
283
in which R6, Ra, Rb, Y and R3 are as defined above,
or to be reacted under palladium coupling conditions, in a basic medium, with a compound of formula (XII):
R6—H (XII)
in which R6′ represents a nitrogenous heterocycle optionally substituted by one or more groups such as are defined for the substituents of the R6 group within the compounds of formula (I),
to yield to the compounds of formula (I/d), a particular case of the compounds of formula (I):
284
in which Ra, Rb, Y and R3 are as defined above and R6, represents an optionally substituted nitrogenous heterocycle as defined in the formula (I),
the compounds of formulae (I/a), (I/b), (I/c) and (I/d) together forming the compounds of formula (I/e):
285
in which Ra, Rb, R1, R2, A, Y and R3 are as defined in the formula (I),
which compounds of formula (I/e) can be treated, for example with 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulphide, to yield to the compounds of formula (I/f), a particular case of the compounds of formula (I):
286
in which Ra, Rb, R1, R2, A, Y and R3 are as defined in the formula (I),
the compounds (I/a) to (I/f) forming all the compounds of the invention, which are purified, if appropriate, according to a conventional purification technique, which can, if desired, be separated into their various isomers according to a conventional separating technique, and which are converted, if appropriate, into their addition salts with a pharmaceutically acceptable acid or base.

94 more elements

18- Process for the preparation of the compounds of formula (I), characterized in that use is made, as starting material, of a compound of formula (II):

287
in which Ra and Rb are as defined in the formula (I) and P1 represents a halogen atom or a triflate group,
which compounds of formula (II) are subjected to oxidation conditions in a basic and polar medium, to give the compounds of formula (III):
288
in which Ra, Rb and P1 are as defined above,
the acid functional group of compounds of formula (III) is esterified by the action of an alcohol in the presence of a strong acid, to yield to the compounds of formula (XX):
289
in which Ra, Rb and P1 are as defined above and P4 represents a linear or branched (C1-C4)alkyl group,
which compounds of formula (XX) are:
either reacted, under basic palladium coupling conditions, with a compound of formula (VII):
290
in which A, R1 and R2 have the same meanings as in the compounds of formula (I),
to yield to the compounds of formula (I/g), a particular case of the compounds of formula (I):
291
in which Ra, Rb, R1, R2, A and P4 are as defined above,
or treated with hexamethylditin in the presence of a palladium catalyst, to yield to the compounds of formula (XXI):
292
in which Ra, Rb and P4 are as defined above,
which compounds of formula (XXI) are reacted:
with a compound of formula (IX):
293
in which R1, R2 and A have the same meanings as in the formula (I) and G10 represents a halogen atom selected from chlorine and bromine or a triflate group,
either in the presence of triphenylphosphinearsenic and of a palladium catalyst, in the case where G10 represents a triflate group,
or in the presence of a cupric halide compound, such as CuBr2, and of a palladium catalyst, under polar solvent conditions, in the case where G10 represents a halogen atom,
to also yield to the compounds of formula (I/g) as described above,
or treated with bis(pinacolato)diborane, followed by an oxidation reaction, to yield to the compounds of formula (XXII):
294
in which Ra, Rb and P4 are as defined above,
which compounds of formula (XXII) are reacted under basic palladium coupling conditions with a compound of formula (IX):
295
in which R1, R2, G10 and A are as defined above,
to also yield to the compounds of formula (I/g) as defined above:
296
in which Ra, Rb, R1, R2 and P4 are as defined above,
or reacted with a compound of formula (IXa):
297
in which A, R1 and R2 are as defined in the formula (I),
either in the presence of triphenylphosphinearsenic and of a palladium catalyst, in the case where P1 in the compounds of formula (XX) represents a triflate group,
or in the presence of a cupric halide compound, such as CuBr2, and of a palladium catalyst, under polar solvent conditions, in the case where P1 in the compounds of formula (XX) represents a halogen atom,
to also yield to the compounds of formula (I/g) as described above,
which compounds of formula (I/g), in the specific case where they represent compounds of formula (I/h), in which A represents a phenyl group, R2 represents a hydrogen atom, R1 represents a hydroxyl group or a halogen atom (Hal) and Ra, Rb and P4 have the same meaning as in the formula (I):
298
can then be treated beforehand with trifluoromethanesulphonic anhydride in the presence of a strong base, in the case where R1 represents a hydroxyl group, to produce the triflate activated derivative,
it then being possible for the said compounds carrying an R1 group taking the definition halogen or triflate:
either to be reacted, under basic conditions and in the presence of a palladium catalyst, with a compound of formula (X):
299
in which R6 is as defined in the formula (I), that is to say that it represents a group selected from aryl and cycloalkyl and a heterocycle, each optionally being substituted,
to yield to the compounds of formula (I/i), a particular case of the compounds of formula (I):
300
in which R6, Ra, Rb and P4 are as defined above,
or to be treated with bis(pinacolato)diborane, followed by an oxidation reaction, to yield to the compounds of formula (XXIII):
301
in which Ra, Rb and P4 are as defined above,
which compounds of formula (XXIII) are reacted, under basic conditions and in the presence of a palladium catalyst, with a compound of formula (Xa):
R6—P2 (Xa)
in which R6 is as defined in the formula (I), that is to say that it represents a group selected from aryl and cycloalkyl and a heterocycle, each optionally being substituted, and P2 represents a halogen atom or a triflate group,
to also yield to the compounds of formula (I/i) as defined above:
302
in which R6, Ra, Rb and P4 are as defined above,
or to be treated with hexamethylditin, in the presence of a palladium catalyst, to yield to the compounds of formula (XXIV):
303
in which Ra, Rb and P4 are as defined above,
which compounds of formula (XXIV) are reacted with a compound of formula (Xa) as defined above:
R6—P2 (Xa)
in which R6 is as defined in the formula (I) and P2 represents a halogen atom or a triflate group,
either in the presence of triphenylphosphinearsenic and of a palladium catalyst, in the case where P2 represents a triflate group,
or in the presence of a cupric halide compound, such as CuBr2, and of a palladium catalyst, under polar solvent conditions, in the case where P2 represents a halogen atom,
to also yield to the compounds of formula (I/i) as defined above:
304
in which R6, Ra, Rb and P4 are as defined above,
or to be reacted with a compound of formula (Xb):
R6—SnMe3 (Xb)
in which R6 is as defined above,
either in the presence of triphenylphosphinearsenic and of a palladium catalyst, in the case where the compounds of formula (I/h) comprise a triflate group,
or in the presence of a cupric halide compound, such as CuBr2, and of a palladium catalyst, under polar solvent conditions, in the case where the compounds of formula (I/h) comprise a halogen atom,
to also yield to the compounds of formula (I/i) as described above,
305
in which R6, Ra, Rb and P4 are as defined above,
the compounds of formulae (I/g), (I/h) and (I/i) together forming the compounds of formula (I/j):
306
in which Ra, Rb, R1, R2, A and P4 are as defined above,
which compounds of formula (I/j) are saponified under basic hydrolysis conditions to yield to the compounds of formula (I/k), a particular case of the compounds of formula (I):
307
in which Ra, Rb, R1, R2 and A are as defined in the formula (I),
which compounds of formula (I/k) are either activated beforehand to the acid chloride by reaction in particular with oxalyl chloride or treated directly, under peptide coupling conditions in the presence, for example, of a coupling agent and in a basic and nonpolar medium, with a compound of formula (V):
HY—R3 (V)
in which Y and R3 have the same meanings as in the compounds of formula (I), to yield to the compounds of formula (I/l), a particular case of the compounds of formula (I):
308
in which A, R1, R2, Ra, Rb, R3 and Y are as defined above,
which compounds of formula (I/l) can be treated, for example with 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulphide, to yield to the compounds of formula (I/m), a particular case of the compounds of formula (I):
309
in which Ra, Rb, R1, R2, A, Y and R3 are as defined in the formula (I),
the compounds (I/g) to (I/m) together forming compounds of the invention, which are purified, if appropriate, according to a conventional purification technique, which can, if desired, be separated into their various isomers according to a conventional separating technique, and which are converted, if appropriate, into their addition salts with a pharmaceutically acceptable acid or base.

90 more elements

Novel thiophene derivatives, their process of preparation and the pharmaceutical compositions which comprise them

Life of this patent

Novel thiophene derivatives, their process of preparation and the pharmaceutical compositions which comprise them

Life of this patent

Abstract

Claims26