Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-11-10
2003-08-12
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S412000, C514S443000, C514S444000, C514S452000, C514S454000, C548S427000, C548S429000, C548S430000, C548S452000, C548S490000, C549S032000, C549S033000, C549S044000, C549S046000, C549S048000, C549S049000, C549S052000, C549S433000, C549S458000, C549S462000, C549S463000, C549S464000
Reexamination Certificate
active
06605632
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to new substituted cyclic compounds having very valuable pharmacological characteristics in respect of melatoninergic receptors.
DESCRIPTION OF THE PRIOR ART
The prior art discloses retroamide chain indoles substituted by amides or carbamates for use as antagonists of GnRH (WO 9721707) and amide chain indoles substituted by amides, carbamates or ureas for use as antihypertensive agents (U.S. Pat. No. 4,803,218).
Retroamide chain benzofuran and benzothiophene compounds substituted by amides or carbamates have also been described as anti-inflammatory agents (EP 685475) or inhibitors of bone resorption.
BACKGROUND OF THE INVENTION
In the last ten years, numerous studies have demonstrated the major role played by melatonin (5-methoxy-N-acetyltryptamine) in numerous physiopathological phenomena and also in the control of circadian rhythm. Its half-life is, however, quite short owing to its being rapidly metabolised. It is thus very useful to be able to provide the clinician with melatonin analogues that are metabolically more stable and that have an agonist or antagonist character on the basis of which a therapeutic effect that is superior to that of the hormone itself may be expected. In addition to their beneficial action on disorders of circadian rhythm (J. Neurosurg. 1985, 63, pp 321-341) and sleep disorders (Psychopharmacology, 1990, 100, pp 222-226), ligands of the melatoninergic system have valuable pharmacological properties in respect of the central nervous system, especially anxiolytic and antipsychotic properties (Neuropharmacology of Pineal Secretions, 1990, 8 (3-4), pp 264-272) and analgesic properties (Pharmacopsychiat., 1987, 20, pp 222-223), and also for the treatment of Parkinson's disease (J. Neurosurg. 1985, 63, pp 321-341) and Alzheimer's disease (Brain Research, 1990, 528, pp 170-174). Those compounds have also shown activity on certain cancers (Melatonin—Clinical Perspectives, Oxford University Press, 1988, pp 164-165), ovulation (Science 1987, 227, pp 714-720), diabetes (Clinical Endocrinology, 1986, 24, pp 359-364), and in the treatment of obesity (International Journal of Eating Disorders, 1996, 20 (4), pp 443-446). Those various effects take place via the intermediary of specific melatonin receptors. Molecular biology studies have shown the existence of a number of receptor sub-types that can bind the hormone (Trends Pharmacol. Sci., 1995, 16, p 50; WO 97.04094). It has been possible to locate some of those receptors and to characterise them for different species, including mammals. In order to be able to understand the physiological functions of those receptors better, it is very valuable to have specific ligands available. Moreover, by interacting selectively with one or other of those receptors, such compounds can be excellent medicaments for the clinician in the treatment of pathologies associated with the melatoninergic system, some of which have been mentioned above.
In addition to the fact that the compounds of the present invention are new, they exhibit very great affinity for melatonin receptors and/or selectivity for one or other of the melatoninergic receptor sub-types.
DETAILED DESCRIPTION OF THE INVENTION
More specifically, the present invention relates to compounds of formula (I):
R—A—R′ (I)
wherein
A represents:
a ring system of formula (II):
wherein
X represents an oxygen, sulphur or nitrogen atom or a group C(H)
q
(wherein q is 0, 1 or 2) or NR
0
(wherein R
0
represents a hydrogen atom, a linear or branched (C
1
-C
6
)alkyl group, an aryl group, an aryl-(C
1
-C
6
)alkyl group in which the alkyl moiety is linear or branched, or SO
2
Ph),
Y represents a nitrogen atom or a group C(H)
q
(wherein q is 0, 1 or 2),
Z represents a nitrogen atom or a group C(H)
q
(wherein q is 0, 1 or 2), but X, Y and Z cannot represent three hetero atoms simultaneously,
B represents a benzene or pyridine nucleus,
the symbol
. . .
means that the bonds may be single or double, it being understood that the valency of the atoms is respected,
wherein R substitutes the ring B and R′ substitutes the ring containing the groups X, Y and Z, or R and R′ substitute the ring B,
a ring system of formula (III):
wherein
X′ represents an oxygen or sulphur atom or a group C(H)
q
(wherein q is 0, 1 or 2),
Y′ represents a group C(H)
q
(wherein q is 0, 1 or 2) or NR
0
wherein R
0
is as defined hereinbefore,
Z′ represents a group C(H)
q
(wherein q is 0, 1 or 2) or NR
0
wherein R
0
is as defined hereinbefore,
T′ represents an oxygen or sulphur atom or a group C(H)
q
(wherein q is 0, 1 or 2),
it being understood that, when Y′ or Z′ represents a hetero atom, the other three variables ((X′, Z′, T′) and (X′, Y′, T′), respectively) cannot represent a hetero atom,
the symbol
. . .
is as defined hereinbefore,
B′ represents:
a benzene nucleus,
a naphthalene nucleus when X′, Y′, Z′ and T′ do not simultaneously represent a group C(H)
q
(wherein q is 0, 1 or 2),
or a pyridine nucleus when X′ and T′ simultaneously represent a group C(H)
q
(wherein q is 0, 1 or 2),
wherein R substitutes the ring B′ and R′ substitutes the ring containing the groups X′, Y′, Z′ and T′, or R and R′ substitute the ring B′,
a ring system of formula (IV):
representing the ring systems (IV
a-d
):
wherein
n is an integer such that 0≦n≦3,
W represents an oxygen, sulphur or nitrogen atom, or a group [C(H)
q
]
p
(wherein q is 0, 1 or 2, and p is 1 or 2) or NR
0
wherein R
0
is as defined hereinbefore,
the symbol
. . .
is as defined hereinbefore,
wherein R′ substitutes the ring
and R substitutes one or other of the two other rings,
or a biphenyl group wherein R substitutes one of the benzene rings and R′ substitutes the other, or R and R′ substitute the same benzene ring,
it being understood that the ring systems of formulae (II), (III) and (IV) and the biphenyl group may be unsubstituted or substituted (in addition to the substituents R and R′) by from 1 to 6 radicals, which may be the same or different, selected from R
a
, OR
a
, COR
a
, COOR
a
, OCOR
a
, OSO
2
CF
3
and halogen atoms,
wherein R
a
represents a hydrogen atom, an unsubstituted or substituted linear or branched (C
1
-C
6
)alkyl group, an unsubstituted or substituted linear or branched (C
2
-C
6
)alkenyl group, an unsubstituted or substituted linear or branched (C
2
-C
6
)alkynyl group, a linear or branched (C
1
-C
6
)polyhaloalkyl group, an unsubstituted or substituted (C
3
-C
8
)cycloalkyl group, an unsubstituted or substituted (C
3
-C
8
)cycloalkyl-(C
1
-C
6
)alkyl group in which the alkyl group is linear or branched, an unsubstituted or substituted (C
3
-C
8
)cycloalkenyl group, an unsubstituted or substituted (C
3
-C
8
)cycloalkenyl-(C
1
-C
6
)alkyl group in which the alkyl group is linear or branched, an aryl group, an aryl-(C
1
-C
6
)alkyl group in which the alkyl moiety is linear or branched, an aryl-(C
1
-C
6
)alkenyl group in which the alkenyl moiety is linear or branched, a heteroaryl group, a heteroaryl-(C
1
-C
6
)alkyl group in which the alkyl moiety is linear or branched, a heteroaryl-(C
1
-C
6
)alkenyl group in which the alkenyl moiety is linear or branched, an unsubstituted or substituted linear or branched (C
1
-C
6
)heterocycloalkyl group, an unsubstituted or substituted heterocycloalkenyl group, a substituted or unsubstituted heterocycloalkyl-(C
1
-C
6
)alkyl group in which the alkyl moiety is linear or branched, or a substituted or unsubstituted heterocycloalkenyl-(C
1
-C
6
)alkyl group in which the alkyl moiety is linear or branched,
R represents:
a group of formula (V):
wherein
Q represents a sulphur or oxygen atom,
R
1
represents a group NR′
a
R″
a
or OR
1
a
(wherein R′
a
and R″
a
, which may be the same or different, may take any of the values of R
a
and may
Bennejean Caroline
Delagrange Philippe
Guillaumet Gerald
Klupsch Frédérique
Langlois Michel
Balasubrasubramanian Venkataraman
Les Laboratoires Servier
The Firm of Hueschen and Sage
LandOfFree
Substituted cyclic compounds, preparation method and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Substituted cyclic compounds, preparation method and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Substituted cyclic compounds, preparation method and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3109862