Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses
The invention concerns the use of PDE2 inhibitors for treating disorders of the central and peripheral nervous system, a method for therapeutic treatment by administering to an animal said inhibitors. More specifically, the invention concerns novel benzodiazepinone derivatives and their uses in therapeutics more particularly for treating pathologies involving activity of a cyclic nucleotide phosphodiesterase type 2. The invention also concerns methods for preparing same and novel synthesis intermediates.
1 - 28 . (canceled)
29 . A method for treating pathologies related to the nervous system (central and peripheral), in particular central, by administering to a subject in need of such treatment at least one phosphodiesterase 2 inhibitor.
30 . The method according to claim 29 , wherein the pathologies are due to a deregulation of the function of a neurotransmitter or to a deficiency in the release of a neurotransmitter, in particular of dopamine.
31 . The method according to claim 29 , wherein the pathologies are selected in the group consisting of depression, schizophrenia, anxiety, bipolar disorder, attention deficit disorders, sleep disorders, obsessive compulsive disorder, fibromyalgia, Tourette's syndrome, pharmacodependence, epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, obesity and Lewy body dementia.
32 . The method according to claim 29 , wherein the pathologies involve the peripheral nervous system and the peripheral organs, in particular pathologies of the type reduced natriuria, acute renal failure, hepatic dysfunction, acute hepatic failure, in particular due to age.
33 . The method according to claim 29 , wherein the pathologies are due to or involve dysfunctions of prolactin secretion, in particular selected in the group consisting of restless legs syndrome, rheumatismal, allergic or auto-inflammatory disorders, more particularly selected in the group consisting of rheumatoid arthritis, rhinitis or asthma.
34 . The method according to claim 29 , wherein the pathologies are selected in the group consisting of anxiety, depression and schizophrenia.
35 . The method according to claim 29 , wherein the PDE2 inhibitors are selected in the group consisting of 1,4-benzodiazepine derivatives.
36 . A compound represented by general formula (I)
in which:
Z represents an oxygen or sulfur atom or a NR 2 group,
R 1 is the hydrogen atom, a (C 1 -C 6 ) alkyl group, a (C 6 -C 18 )aryl group or a (C 1 -C 6 )alkyl(C 6 -C 18 )aryl or (C 6 -C 18 )aryl(C 1 -C 4 )alkyl group,
R 2 is a hydrogen atom, a (C 1 -C 6 ) alkyl group, a (C 6 -C 18 )aryl group or a (C 1 -C 6 )alkyl(C 6 -C 18 )aryl or (C 6 -C 18 )aryl(C 1 -C 4 )alkyl group,
R 1 and R 2 taken together can optionally form a linear or branched hydrocarbon chain having from 2 to 6 carbon atoms, possibly containing one or several other double bonds and/or possibly interrupted by an oxygen, sulfur or nitrogen atom,
R 3 and R 3′ , which are the same or different, represent the hydrogen atom, a (C 1 -C 12 ) alkyl, (C 3 -C 6 ) cycloalkyl, (C 6 -C 18 ) aryl, (C 6 -C 18 )aryl(C 1 -C 4 )alkyl, (C 1 -C 12 )alkyl(C 6 -C 18 )aryl group or a (C 5 -C 18 ) heterocycle, aromatic or not, containing 1 to 3 heteroatoms, a NO 2 , CF 3 , CN, NR′R″, SR′, OR′, COOR′, CONR′R″ or NHCOR′R″ group, R′ and R″, independently of each another, being selected in the group consisting of the hydrogen atom, a (C 1 -C 6 ) alkyl, (C 3 -C 6 ) cycloalkyl, (C 6 -C 12 ) aryl group and a (C 5 -C 12 ) heterocycle, aromatic or not, containing 1 to 3 heteroatoms;
R 5 represents a phenyl group substituted at least in position 3, a naphthyl group, a (C 5 -C 18 ) heterocycle, aromatic or not, containing 1 to 3 heteroatoms, selected in the group consisting of the pyridyl, isoquinolyl, quinolyl and piperazinyl group, provided that when R 5 is a naphthyl group substituted in position 6, then the latter is not attached to the rest of the molecule in position 2, or when R 5 is a pyridyl group, then it is not attached to the rest of the molecule in position 4, or when R 5 is a tetrahydro 1,2,3,4-isoquinolyl group, then it is not attached to the rest of the molecule in position 2,
when R 5 represents a phenyl group substituted at least in position 3, said substituent being selected in the group consisting of: an alkyl, halogenoalkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heterocycle, heterocycloalkyl group, a OH, ═O, NO 2 , NH 2 , CN, CF 3 , COR′, COOR′, (C 1 -C 6 )alkoxy, (di)(C 1 -C 6 )alkylamino, NHCOR′, CONR′R″ group, in which R′ and R″ are such as defined hereinabove, CHO, CONH2, phenyl optionally substituted, in particular by an acetyl group, by a halogen atom (Cl), by a CONH2 group or by a CN, prop-1-ynyl optionally substituted, in particular by a benzyloxy or tert-butyl carbamate, hex-1-ynyl optionally substituted, in particular by a CN or NH2, pentyl optionally substituted, in particular by a CONH2, hexyl, piperidinyl group optionally substituted, in particuar by a prop-1-ynyl, benzylaminomethyl, acetamide (CH3CONH), aminomethyl, NH2CS—, 4-phenyl-1, 3-thiazol-2-yl, —CONHBenzyl, —COOEthyl, —CONHiPropyl, —CONH—(CH2)n—CONH2 (n representing a whole number from 1 to 6), —CONR′R″ group, with R′ and R″, which are the same or different, representing a C 1 -C 6 alkyl group or a hydrogen atom, -(4-benzylpyperazin-1-yl)carbonyl, —CONH—(CH2)n-phenyl (n representing a whole number from 1 to 6), imidazolyl, piperazinyl optionally substituted, in particular by a phenyl group,
R 7 and R 8 , independently of each other, are selected in the group consisting of the hydrogen atom, a halogen atom or a OR 10 , group in which R 10 represents a hydrogen atom, a (C 1 -C 6 ) alkyl, (C 3 -C 6 ) cycloalkyl, (C 6 -Cl 2 ) aryl group, or a (C 5 -C 12 ) heterocycle, aromatic or not, containing 1 to 3 heteroatoms, at least one of the groups R 7 and R 8 representing a OR 10 group such as defined hereinabove,
R 6 and R 9 , independently of each other, are selected in the group consisting of the hydrogen atom, a halogen atom, an alkyl, cycloalkyl, alkenyl, alkynyl group, an aryl, aralkyl, heterocycle, heterocycloalkyl group and a OR 10 group, R 10 being such as defined hereinabove,
the alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, phenyl, naphthyl, heterocycle, heterocycloalkyl group or the hydrocarbon chain defined hereinabove being optionally substituted by one or more substituents, which are the same or different, preferably selected in the group consisting of a halogen atom, an alkyl, halogenoalkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heterocycle, heterocycloalkyl group, a OH, ═O, NO 2 , NH 2 , CN, CF 3 , COR′, COOR′, (C 1 -C 6 )alkoxy, (di)(C 1 -C 6 )alkylamino, NHCOR′ and CONR′R″ group, in which R′ and R″ are such as defined hereinabove, the substitutents also being optionally substituted,
and one of the salts thereof,
with the exception of compounds represented by formula (I) in which
R1 l is an alkyl group, R3 and R′3 are hydrogen atoms, R6 and R9 are hydrogen atoms, R5 is a phenyl group substituted at least in position 3 by a methoxy group,
R1 is an alkyl group or a hydrogen atom, R3 and R′3 are hydrogen atoms, R6 and R9 are hydrogen atoms, R5 is a phenyl group substituted only in position 3 by a chlorine or bromine atom,
R1 is an alkyl group, R3 and R′3 are hydrogen atoms, R6 and R9 are hydrogen atoms, R5 is a phenyl group substituted at least in position 3 by a CH2OH group,
R1 is a hydrogen atom, R3 and R′3 are hydrogen atoms, R6 and R9 are hydrogen atoms, R5 is a phenyl group substituted only in position 3 by a CF3 group,
R1 is an alkyl group, R3 and R′3 are hydrogen atoms, R6 and R9 are hydrogen atoms, R5 is a phenyl group substituted in positions 3 and 5 by a CF3 group,
R1 is an alkyl group, R3 and R′3 are hydrogen atoms, R6 and R9 are hydrogen atoms, R7 and R8 are methoxy groups, R5 is a phenyl group substituted in positions 3 by a phenyl group,
R1 is an alkyl group, R3 and R′3 are hydrogen atoms, R6 and R9 are hydrogen atoms, R7 and R8 are methoxy groups, R5 is a phenyl group substituted in positions 3 by a phenylethynyl group.
37 . The compound represented by formula (I) according to claim 36 , in which R 5 is a phenyl group substituted at least in position 3.
38 . The compound represented by formula (I) according to claim 36 , wherein R 5 is a phenyl group substituted at least in position 3 and wherein the substituent is selected in the group consisting of: CHO, CN, CONH2, NO2, CF3, NH2, halogen atom (Cl), (C1-C6) alkyl, phenyl optionally substituted, in particular by an acetyl group, by a halogen atom (Cl), by a CONH2 group or by a CN, prop-1-ynyl group optionally substituted, in particular by a benzyloxy or tert-butyl carbamate, hex-1-ynyl group optionally substituted, in particular by a CN or NH2 group, pentyl optionally substituted, in particular by a CONH2, hexyl, piperidinyl optionally substituted, in particular by a prop-1-ynyl, benzylaminomethyl, acetamide (CH3CONH), aminomethyl, NH2CS—, 4-phenyl-1,3-thiazol-2-yl, —CONHBenzyl, —COOEthyl, —CONHiPropyl, —CONH—(CH2)n—CONH2 (n representing a whole number from 1 to 6), —CONR′R″ group, with R′ and R″, which are the same or different, representing a C1 to C6 alkyl group or a hydrogen atom, -(4-benzylpyperazin-1-yl)carbonyl, —CONH—(CH2)n-phenyl (n representing a whole number from 1 to 6), imidazolyl, piperazinyl group optionally substituted, in particular by a phenyl group.
39 . The compound represented by formula (I) according to claim 36 , in which R5 is a phenyl group substituted in positions 3 and 4, in particular by a hydrocarbon chain possibly containing at least one heteroatom, such as oxygen, like the methylenedioxy (—O—CH2—O—) chain forming a ring with the phenyl group to which it is attached.
40 . The compound represented by formula (I) according to claim 36 , in which R5 is the 3-pyridyl, 4-isoquinolyl, piperazinyl group optionally substituted, in particular in position 4 by an aryl group, such as phenyl.
41 . The compound represented by formula (I) according to claim 36 , in which Z represents a sulfur atom or —NR2, with in particular R2 forming a ring of the imidazole type with R1.
42 . The compound represented by formula (I) according to claim 36 , in which
Z is the oxygen atom, and/or
R 7 and R 8 , independently of each other, represent a OR 10 group in which R 10 is a (C 1 -C 6 ) alkyl group, preferably an ethyl or methyl group, advantageously methyl, and/or
R 7 and R 8 each represent an ethoxy or methoxy group, advantageously methoxy, or one represents a hydrogen atom and the other an ethoxy or methoxy group, advantageously methoxy, and/or
R 6 and R 9 , which are the same or different, represent the hydrogen atom, a halogen atom, a phenyl group, a (C 1 -C 6 ) alkyl group or a OR 10 group in which R 10 is a (C 1 -C 6 ) alkyl group, preferably an ethyl or methyl group, and/or
R 3 and R 3 ′, which are the same or different, represent a hydrogen atom, and/or
R 1 is a (C1-C6) alkyl, (C 6 -C 18 ) aryl group, such as phenyl, (C 6 -C 18 )aryl(C 1 -C 4 )alkyl group such as benzyl optionally substituted, or (C 1 -C 12 )alkyl(C 6 -C 18 )aryl group.
43 . The compound represented by formula (I) according to claim 36 , in which R 1 represents a hydrogen atom or a (C 1 -C 3 ) alkyl, (C 6 -C 18 ) aryl (for example: phenyl), (C 6 -C 18 )aryl(C 1 -C 4 )alkyl (for example: benzyl), (C 1 -C 12 )alkyl(C 6 -C 18 )aryl group, said group being optionally substituted.
44 . The compound represented by formula (I) according to claim 36 , in which R 5 is a phenyl group substituted by:
(a) one or more OR′ groups, in particular methoxy or ethoxy, or
(b) a COR′ group, in particular acetyl or aldehyde, or
(c) a CONR′R″ group, in particular CONH2, or
(d) a CN group, or
(e) a trifluoromethyl group, or
(f) an alkyl group, for example methyl, or alkynyl group, for example hexynyl or propynyl, or
(g) an aryl or heterocycle group, in particular phenyl, furyl, pyridyl, piperidine, thiazole or thienyl, said aryl or heterocycle itself being optionally substituted by one or more groups preferably selected from groups (a)-(g).
45 . The compound represented by formula (I) according to claim 36 , in which at least one group R 7 or R 8 represents OR 10 where R 10 represents a (C 1 -C 6 ) alkyl or (C 3 -C 6 ) cycloalkyl group.
46 . The compound represented by formula (I) according to claim 36 , in which at least one group R 7 or R 8 represents OR 10 where R 10 represents a (C 1 -C 6 ) alkyl or (C 3 -C 6 ) cycloalkyl group and at least one of the groups R7 and R8, advantageously both, represents a methoxy group.
47 . The compound according to claim 36 , wherein said compound is selected from the following compounds:
3-(7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 3a
7,8-dimethoxy-[5-(3-trifluoromethyl)phenyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 3d
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-benzonitrile, 4a
3-[1-(4-chlorobenzyl)-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]-benzonitrile, 4c
3-[1-(3,4-chlorobenzyl)-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]-benzonitrile, 4d
3-[7,8-dimethoxy-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]-benzonitrile, 4e
3-[1-(3-chlorobenzyl)-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]-benzonitrile, 4f
3-{7,8-dimethoxy-2-oxo-1-[3-(trifluoromethyl)benzyl]-2,3-dihydro-1H-1,4-benzodiazepin-5-yI]-benzonitrile, 4g
3-[1-(2-chlorobenzyl)-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]-benzonitrile, 4h
3-{7,8-dimethoxy-2-oxo-1-[4-(trifluoromethyl)benzyl]-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]-benzonitrile, 4i
3-[7,8-dimethoxy-2-oxo-1-(2-phenylethyl)-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]-benzonitrile, 4j
3-(i -ethyl-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 4k
3-(7,8-dimethoxy-1-propyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 4l
3-(i -benzyl-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 4m
ethyl[5-(3-cyanophenyl)-7,8-dimethoxy-2-oxo-2,3-dihydro-i H-1,4-benzodiazepin-1-yl]acetate, 4n
7,8-dimethoxy-i -methyl-[5-(3-trifluoromethyl)phenyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 4p
7,8-dimethoxy-1-ethyl-5-[3-(trifluoromethyl)phenyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 4q
5-[3-(trifluoromethyl)phenyl]-7,8-dimethoxy-1-n-propyl-1,3-dihydro-1,4-benzodiazepin-2-one, 4r
1-benzyl-5-[3-(trifluoromethyl)phenyl]-7,8-dimethoxy-1,3-dihydro-1,4-benzodiazepin-2-one, 4s
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-benzamide 5a
3-(6-bromo-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5b
3-(7,8-dimethoxy-1-methyl-2-oxo-6-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5c
3-(9-bromo-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5d
3-(7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5e
3-(7,8-dimethoxy-1-propyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5f
3-(1-ethyl-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yI)benzamide, 5g
3-(1-benzyl-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5h
ethyl{5-[3-(aminocarbonyl)phenyl]-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-1-yl}acetate, 5i
3-(7,8-dimethoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl) benzamide, 5j
3-[3-(3,4-dichlorobenzyl)-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]benzamide, 5k
3-(8-methoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5l
3-(7,8-dimethoxy-1-methyl-2-oxo-9-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5m
3-(6,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5n
3-(6,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5o
tert-butyl-3-[3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)phenyl]propynylcarbamate, 6a
7,8-dimethoxy-5-(3′-hex-1-ynylphenyl)-l -N-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 6b
7,8-dimethoxy-1-methyl-5-[3-(3-piperidin-1-ylprop-1-ynyl)phenyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 6c
6-[3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)phenyl]hex-5-ynenitrile, 6d
7,8-dimethoxy-5-(3′-hexylphenyl)-1-N-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 6e
5-[3-(3-aminopropyl)phenyl-7,8-dimethoxy-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one trifluoro 6 acetate, 6h
6-[3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)phenyl]hexanamide, 6i
5-(4′-chloro-1,1′-biphenyl-3-yl)-7,8-dimethoxy-i -methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 6j
5-{3-[3-(benzyloxy)prop-1-ynyl]phenyl}-1-ethyl-7,8-dimethoxy-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 6k
3′-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-1,1′-biphenyl-3-carbonitrile, 6l
3 ′-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-1,1′-biphenyl-4-carbonitrile, 6m
3′-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-1,1′-biphenyl-4-carboxamide, 6n
3′-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-1,1′-biphenyl-3-carboxamide, 6o
3-[3-(3,4-dichlorobenzyl)-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]benzonitrile, 7b
7,8-dimethoxy-1,3-dimethyl-5-(3-trifluoromethylphenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 7c
3-(7,8-dimethoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 7d
5-[3-(aminomethyl)phenyl]-7,8-dimethoxy-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 8a
N-[3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzyl]acetamide, 8b
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)thiobenzamide, 9a
7,8-dimethoxy-1-methyl-5-[3-(4-phenyl-1,3-thiazol-2-yl)phenyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 9b
5-(3-cyanophenyl)-7,8-dimethoxy-1,3-dihydro-2H-1,4-benzodiazepin-2-thione, 10d
3-(8,9-dimethoxy-4H-imidazo[1,2-a][1,4]benzodiazepin-6-yl)benzonitrile, 11 a
3-(8,9-dimethoxy-4H-imidazo[1,2-a][1,4]benzodiazepin-6-yl)benzamide, 11b
3-(7,8-dimethoxy-2-methylamino-1,3-dihydro-3H-1,4-benzodiazepin-5-yl)benzonitrile, 12a
7,8-dimethoxy-1-methyl-5-(3-pyridyl)-1,3-dihydro-1,4-benzodiazepin-2-one, 17b
7,8-dimethoxy-1-methyl-5-(3-nitrophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one, 17c
5-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-2-benzonitrile, 17d
5-(3-acetylphenyl)-7,8-dimethoxy-1-methyl-1,3-dihydro-1,4-benzodiazepin-2-one, 17e
5-(4-isoquinolinyl)-7,8-dimethoxy-1-methyl-1,3-dihydro-1,4-benzodiazepin-2-one, 17f
7,8-dimethoxy-5-(3-hydroxymethylphenyl)-1-methyl-3-propyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 17h
5-(3-aminophenyl)-7,8-dimethoxy-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 17i
5-(3,4-dichlorophenyl)-7,8-dimethoxy-1-methyl-1,3-dihydro-1,4-benzodiazepin-2-one, 17j
7,8-dimethoxy-1-methyl-5-(3-methylphenyl)-1,3-dihydro-1,4-benzodiazepin-2-one, 17k.
5-(3-formylphenyl)-7,8-dimethoxy-1-methyl-1,3-dihydro-1,4-benzodiazepin-2-one, 17l
5-[3-(benzylaminomethyl)phenyl]-7,8-dimethoxy-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one hydrochloride, 17m
N-[3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl) phenyl]acetamide, 17n
7,8-dimethoxy-1-methyl-5-(3,4-methylenedioxyphenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 17o
3-(7-hydroxy-8-methoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 22b
3-(6-bromo-7-hydroxy-8-methoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 23b
3-(9-bromo-8-hydroxy-7-methoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 23d
3-(6-bromo-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 24b
3-(7,8-dimethoxy-1-methyl-2-oxo-6-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 25b
3-(7,8-dimethoxy-1-methyl-2-oxo-9-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 25a
tert-butyl-3-[5-(cyanophenyl)-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-9-yl)phenyl]prop-2-ynylcarbamate, 25c
methyl(2E)-3-[5-(cyanophenyl)-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-9-yl)phenyl]acrulate, 25d
tert-butyl-3-[5-(cyanophenyl)-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-6-yl)phenyl]prop-2-ynylcarbamate, 25e
[9-(3-aminoethynyl)-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]benzonitrile, 25f
[6-(3-aminoethynyl)-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl]benzonitrile, 25g
3-(8-methoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 28a
3-(6-methoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 28b
3-(7-methoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 28c
6-methoxy-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 28d
7-methoxy-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 28e
9-bromo-7,8-dimethoxy-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 28f
3-(6,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 28g
3-(7-bromo-6,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 28h
3-(8-methoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 29a
3-(6,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 29b
3-(7-bromo-6,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 29c
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)methyl benzoate, 34a
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzoic acid, 35a
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)N-isopropylbenzamide, 36a
N-benzyl-3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl) benzamide, 36b
N-(6-amino-6-oxohexyl)-3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 36c
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yi)-N, N-dimethylbenzamide 36d
5-{3-[(4-benzylpyperazin-1-yl)carbonyl]phenyl}7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-2-one, 36e
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-N-(3-phenylpropyl)benzamide, 36f.
48 . The compound according to claim 36 , wherein said compound is selected from the following compounds:
3-(1-benzyl-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzonitrile, 4m
7,8-dimethoxy-1-methyl-[5-(3-trifluoromethyl)phenyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 4p
3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5a
3-(6-bromo-7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)benzamide, 5b
tert-butyl-3-[3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)phenyl]propynylcarbamate, 6a
7,8-dimethoxy-5-(3′-hex-1-ynylphenyl)-1-N-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 6b
6-[3-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)phenyl]hex-5-ynenitrile, 6d
7,8-dimethoxy-5-(3′-hexylphenyl)-1-N-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 6e
5-(4′-chloro-1,1′-biphenyl-3-yl)-7,8-dimethoxy-i -methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 6j
3′-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-1 ,1′-biphenyl-4-carbonitrile, 6m
3′-(7,8-dimethoxy-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)-1,1 ′-biphenyl-4-carboxamide, 6n
3-(3,4-dichlorobenzyl)-1-ethyl-7,8-dimethoxy-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 7a
7,8-dimethoxy-1-methyl-5-[3-(4-phenyl-1,3-thiazol-2-yl)phenyl]-1,3-dihydro-2H-1,4-benzodiazepin-2-one, 9b
7,8-dimethoxy-1-methyl-5-(3-pyridyl)-1,3-dihydro-1,4-benzodiazepin-2-one, 17b.
49 . A pharmaceutical composition comprising at least one compound such as defined in claim 36 and a pharmaceutically acceptable vehicle or excipient.
50 . A method for treating pathologies involving the central nervous system, in particular due to a deregulation of the function of a neurotransmitter or to a deficiency in the release of a neurotransmitter, by administering to a subject in need of such treatment at least one compound such as defined in claim 36 .
51 . The method according to claim 50 , wherein the pathology is selected in the group consisting of depression, schizophrenia, anxiety, bipolar disorder, attention deficit disorders, sleep disorders, obsessive compulsive disorder, fibromyalgia, Tourette's syndrome, pharmacodependence, epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, obesity and Lewy body dementia.
52 . A method for treating pathologies involving the peripheral nervous system and peripheral organs in general, in particular pathologies of the type reduced natriuria, acute renal failure, hepatic dysfunction, acute hepatic failure, in particular due to age, and pathologies due to or involving dysfunctions of prolactin secretion, such as restless legs syndrome, rheumatismal, allergic or auto-inflammatory disorders, such as rheumatoid arthritis, rhinitis and asthma, by administering to a subject in need of such treatment a compound such as defined in claim 36 .
53 . A method for treating disorders of the central or peripheral nervous system, of chronic or acute nature, by administering to a subject in need of such treatment a compound such as defined in claim 36 .
54 . A method for treating memory impairment or cognitive impairment, in particular mild cognitive impairment, for treating neurodegenerative diseases, or for treating obesity, by administering to a subject in need of such treatment a compound such as defined in claim 36.