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US 2005/0239771 A1Published application
Respiratory syncytial virus replication inhibitors
AssigneeJanssen Pharmaceutica NV
InventorsFrans Janssens, Kathleen Meersman, François Sommen, Jérôme Guillemont, Jean Lacrampe, Koenraad Jozef Andries
Life of this patent
Estimating the term…
Abstract
This invention concerns the use of compounds of formula (I) wherein -a1=a2−a3=a4- is a radical of for CH═CH—, —N═CH—CH═CH—, —CH═N—CH═CH—, —CH═CH—N═CH—, —CH═CH—CH═N— wherein each hydrogen atom may optionally be substituted; Q is a radical of formulas (b-1), (b-2), (b-3), (b-4), (b-5), (b-6), (b-7), (b-8). G is a direct bond or C1-10alkanediyl; R1 is an optionally substituted monocyclic heterocycle; for the manufacture of a medicament for the treatment of viral infections, in particular RSV infections. Certain compounds of formula (I) are new.
Claims13
1-17. (canceled)
A compound of formula (I′):
- an addition salt, or stereochemically isomeric form thereof,
- wherein -a1=a2−a3=a4- represents a radical of formula
- —CH═CH—CH═CH— (a-1);
- wherein each hydrogen atom in the radicals (a-1) may optionally be replaced by halo, C1-6alkyl, nitro, amino, hydroxy, C1-6alkyloxy, polyhaloC1-6alkyl, carboxyl, aminoC1-6alkyl, mono- or di(C1-4alkyl)aminoC1-6alkyl, C1-6alkyloxycarbonyl, hydroxyC1-6alkyl, or a radical of formula
- wherein Z is O, CH—C(═O)—NR5aR5b, CH2, CH—C1-6alkyl, N—OH or N—O—C1-6alkyl;
- Q is a radical of formula
- wherein
- Y1 is a bivalent radical of formula —NR2— or —CH(NR2R4)—;
- X1 is NR4, S, S(═O), S(═O)2, O, CH2, C(═O), C(═CH2), CH(OH), CH(CH3), CH(OCH3), CH(SCH3), CH(NR5aR5b), CH2—NR4 or NR4—CH2;
- X2 is a direct bond, CH2, C(═O), NR4, C1-6alkyl-NR4, NR4—C1-6alkyl;
- u is 2 or 3;
- v is 2;
- and
- whereby each hydrogen atom in the carbocycles and the heterocycles defined in radicals (b-4), (b-5), and (b-6) may optionally be replaced by R3;
- with the proviso that when R3 is hydroxy or C1-6alkyloxy, then R3 can not replace a hydrogen atom in the α position relative to a nitrogen atom;
- G is a direct bond or C1-10alkanediyl;
- R1 is a monocyclic heterocycle selected from pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyrrolyl, imidazolyl and pyrazolyl;
- and each heterocycle may optionally be substituted with 1 or where possible more substituents selected from halo, hydroxy, amino, cyano, carboxy, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, C1-6alkyloxyC1-6alkyl, aryl, arylC1-6alkyl, arylC1-6alkyloxy, hydroxyC1-6alkyl, mono- or di(C1-6alkyl)amino, mono- or di(C1-6alkyl)aminoC1-6alkyl, polyhaloC1-6alkyl, C1-6alkylcarbonylamino, C1-6alkyl-SO2—NR5c—, aryl-SO2—NR5c—, C1-6alkyloxycarbonyl, —C(═O)—NR5cR5d, HO(—CH2—CH2—O)n—, halo(-CH2—CH2—O)n—, C1-6alkyloxy(-CH2—CH2—O)n—, arylC1-6alkyloxy(-CH2—CH2—O)n— and mono- or di(C1-6alkyl)amino(-CH2—CH2—O)n—;
- each n independently is 1, 2, 3 or 4;
- R2 is hydrogen, formyl, pyrrolidinyl, piperidinyl, homopiperidinyl, C3-7cycloalkyl substituted with N(R6)2, or C1-10alkyl substituted with N(R6)2 and optionally with a second, third or fourth substituent selected from amino, hydroxy, C3-7cycloalkyl, C2-5alkanediyl, piperidinyl, mono- or di(C1-6alkyl)amino, C1-6alkyloxycarbonylamino, aryl and aryloxy;
- R3 is hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy, arylC1-6alkyl or arylC1-6alkyloxy;
- R4 is hydrogen, C1-6alkyl or arylC1-6alkyl;
- R5a, R5b, R5b and R5d each independently are hydrogen or C1-6alkyl;
- or
- R5a and R5b, or R5c and R5d taken together form a bivalent radical of formula —(CH2)s— wherein s is 4 or 5;
- R6 is hydrogen, C1-6alkyl, formyl, hydroxyC1-6alkyl, C1-6alkylcarbonyl or C1-6alkyloxycarbonyl;
- aryl is phenyl or phenyl substituted with 1 or more substituents selected from halo, hydroxy, C1-6alkyl, hydroxyC1-6alkyl, polyhaloC1-6alkyl, and C1-6alkyloxy;
- provided:
- that when G is methylene, and R1 is 2-pyridyl, 3-pyridyl, 6-methyl-2-pyridyl, 2-pyrazinyl or 5-methyl-imidazol-4-yl, then Q is other than
26 more elements
A compound of formula (I′):
- an addition salt, or stereochemically isomeric form thereof,
- wherein -a1=a2−a3=a4- represents a radical of formula
- —CH═CH—CH═CH— (a-1);
- wherein each hydrogen atom in the radicals (a-1) may optionally be replaced by halo, C1-6alkyl, nitro, amino, hydroxy, C1-6alkyloxy, polyhaloC1-6alkyl, carboxyl, aminoC1-6alkyl, mono- or di(C1-4alkyl)aminoC1-6alkyl, C1-6alkyloxycarbonyl, hydroxyC1-6alkyl, or a radical of formula
- wherein Z is O, CH—C(═O)—NR5aR5b, CH2, CH—C1-6alkyl, N—OH or N—O—C1-6alkyl;
- Q is a radical of formula
- wherein
- Y1 is a bivalent radical of formula —NR2— or —CH(NR2R4)—;
- X1 is NR4, S, S(═O), S(═O)2, O, CH2, C(═O), C(═CH2), CH(OH), CH(CH3), CH(OCH3), CH(SCH3), CH(NR5aR5b), CH2—NR4 or NR4—CH2;
- X2 is a direct bond, CH2, C(═O), NR4, C1-6alkyl-NR4, NR4—C1-6alkyl;
- u is 2 or 3;
- v is 2;
- and
- whereby each hydrogen atom in the carbocycles and the heterocycles defined in radicals (b-4), (b-5), and (b-6) may optionally be replaced by R3;
- with the proviso that when R3 is hydroxy or C1-6alkyloxy, then R3 cannot replace a hydrogen atom in the α position relative to a nitrogen atom;
- G is a direct bond or C1-10alkanediyl;
- R1 is a monocyclic heterocycle selected from pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyrrolyl, imidazolyl and pyrazolyl;
- and each heterocycle may optionally be substituted with 1 or where possible more substituents selected from halo, hydroxy, amino, cyano, carboxy, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, C1-6alkyloxyC1-6alkyl, aryl, arylC1-6alkyl, arylC1-6alkyloxy, hydroxyC1-6alkyl, mono- or di(C1-6alkyl)amino, mono- or di(C1-6alkyl)aminoC1-6alkyl, polyhaloC1-6alkyl, C1-6alkylcarbonylamino, C1-6alkyl-SO2—NR5c—, aryl-SO2—NR5c—, C1-6alkyloxycarbonyl, —C(═O)—NR5cR5d, HO(—CH2—CH2—O)n—, halo(-CH2—CH2—O)n—, C1-6alkyloxy(-CH2—CH2—O)n—, arylC1-6alkyloxy(-CH2—CH2—O)n— and mono- or di(C1-6alkyl)amino(-CH2—CH2—O)n—;
- each n independently is 1, 2, 3 or 4;
- R2 is hydrogen, formyl, pyrrolidinyl, piperidinyl, homopiperidinyl, C3-7cycloalkyl substituted with N(R6)2, or C1-10alkyl substituted with N(R6)2 and optionally with a second, third or fourth substituent selected from amino, hydroxy, C3-7cycloalkyl, C2-5alkanediyl, piperidinyl, mono- or di(C1-6alkyl)amino, C1-6alkyloxycarbonylamino, aryl and aryloxy;
- R3 is hydrogen, hydroxy, C1 6alkyl, C1-6alkyloxy, arylC1-6alkyl or arylC1-6alkyloxy;
- R4 is hydrogen, C1-6alkyl or arylC1-6alkyl;
- R5a, R5b, R5c and R5d each independently are hydrogen or C1-6alkyl;
- or
- R5a and R5b, or R5c and R5d taken together form a bivalent radical of formula —(CH2)s— wherein s is 4 or 5;
- R6 is hydrogen, C1-4alkyl, formyl, hydroxyC1-6alkyl, C1-6alkylcarbonyl or C1-6alkyloxycarbonyl;
- aryl is phenyl or phenyl substituted with 1 or more substituents selected from halo, hydroxy, C1-6alkyl, hydroxyC1-6alkyl, polyhaloC1-6alkyl, and C1-6alkyloxy;
- provided:
- that the compound of formula I′ is other than:
- (±)-N-[1-(2-amino-ethyl)-4-piperidinyl]-[1 -(2-(2-pyridinyl)-ethyl)-1H-2-benzimidazolyl]-amine;
- (±)-N-[4-piperidinyl]-{1-[2-(6-methyl-2-pyridinyl)ethyl]-1H-2-benzimidazolyl}amine;
- 1-[2-(6-methyl-2-pyridinyl)-ethyl]-2-(4-piperidinyloxy)-1H-benzimidazole;
- or
- 1-[2-(6-methyl-2-pyridinyl)-ethyl]-2-(4-piperidinylmethyl)-1H-benzimidazole;
- and
- that when G is methylene, and R1 is 2-pyridyl, 3-pyridyl, 6-methyl-2-pyridyl, 2-pyrazinyl or 5-methyl-imidazol-4-yl, then Q is other than
33 more elements
A compound selected from the group consisting of:
- (±)-2-[[2-[[1-(2-amino-3-methylbutyl)-4-piperidinyl]amino]-7-methyl-3H-imidazo[4,5-b]pyridin-3-yl]methyl]-6-methyl-3-pyridinol;
- 4-[[3-[[5-(methoxymethyl)-2-furanyl]methyl]-3H-imidazo[4,5-b]pyridine-2-yl]methyl]-1-piperidineetanamine;
- N-[1-(2-aminoethyl)-4-piperidinyl]-3-[(2,4-dimethyl-5-oxazolyl)methyl]-3H-imidazo[4,5-b]pyridin-2-amine;
- 4-[[3-[(2-methyl-5-oxazolyl)methyl]-3H-imidazo[4,5-b]pyridin-2-yl]methyl]-1-piperazineethanamine;
- ethyl 4-[[3-[(3-hydroxy-6-methyl-2-pyridinyl)methyl]-7-methyl-3H-imidazo[4,5-b]pyridine-2-yl]amino]-1-piperidinecarboxylate;
- and an addition salts, and stereochemically isomeric forms thereof,
3 more elements
Dependencies are inferred from the claim text.